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CIRRHOSIS

INTRODUCTION Cirrhosis represents a late stage of progressive hepatic fibrosis


characterized by distortion of the hepatic architecture and the formation of regenerative
nodules. It is generally considered to be irreversible in its advanced stages, at which
point the only treatment option may be liver transplantation. However, reversal of
cirrhosis (in its earlier stages) has been documented in several forms of liver disease
following treatment of the underlying cause. Patients with cirrhosis are susceptible to a
variety of complications, and their life expectancy is markedly reduced. (See "Cirrhosis in
adults: Overview of complications, general management, and prognosis", section on
'Prognosis'.)
This topic will review the etiologies, clinical manifestations, and diagnosis of cirrhosis. An
overview of the complications, prognosis, and general management of cirrhosis is
discussed separately. (See "Cirrhosis in adults: Overview of complications, general
management, and prognosis".)
ETIOLOGIES AND CLASSIFICATION There are numerous causes of liver disease that can
result in cirrhosis, either by causing chronic hepatic inflammation or cholestasis. The two
most common causes of cirrhosis in the United States are alcoholic liver disease and
hepatitis C, which together accounted for approximately one-half of patients on the liver
transplantation wait list in 2011 [1].
In developed countries, common causes of cirrhosis include [2]:
Chronic viral hepatitis (hepatitis B, C)
Alcoholic liver disease
Hemochromatosis
Nonalcoholic fatty liver disease
Less common causes include:
Autoimmune hepatitis
Primary and secondary biliary cirrhosis
Primary sclerosing cholangitis
Medications (eg, methotrexate, isoniazid)
Wilson disease
Alpha-1 antitrypsin deficiency
Celiac disease
Idiopathic adulthood ductopenia
Granulomatous liver disease
Idiopathic portal fibrosis

Polycystic liver disease


Infection (eg, brucellosis, syphilis, echinococcosis, schistosomiasis)
Right-sided heart failure
Hereditary hemorrhagic telangiectasia
Veno-occlusive disease
Cirrhosis was historically classified morphologically as micronodular, macronodular, or
mixed [3]. Micronodular cirrhosis, characterized by nodules less than 3 mm in diameter,
was believed to be caused by alcohol, hemochromatosis, cholestatic causes of cirrhosis,
and hepatic venous outflow obstruction. Macronodular cirrhosis, characterized by various
sized nodules larger than 3 mm, was believed to be secondary to chronic viral hepatitis.
Although important from a historic perspective, the morphological classification system
has a number of limitations and has thus largely been abandoned. First, it is relatively
nonspecific with regard to etiology. Second, the morphologic appearance of the liver may
change as the liver disease progresses; micronodular cirrhosis usually progresses to
macronodular cirrhosis [4]. Third, serological markers available today are more specific
than morphological appearance of the liver for determining the etiology of cirrhosis. As
an example, antimitochondrial antibodies have a specificity of 98 percent for primary
biliary cirrhosis [5]. Finally, accurate assessment of liver morphology can only be
achieved at surgery, laparoscopy, or autopsy, while in today's clinical practice there are
less invasive means to make an etiologic diagnosis.
CLINICAL MANIFESTATIONS The clinical manifestations of cirrhosis may include
nonspecific symptoms (eg, anorexia, weight loss, weakness, fatigue) or signs and
symptoms of hepatic decompensation (jaundice, pruritus, signs of upper gastrointestinal
bleeding, abdominal distension from ascites, confusion due to hepatic encephalopathy)
(table 1). Physical examination findings may include jaundice, spider angiomata,
gynecomastia, ascites, splenomegaly, palmar erythema, digital clubbing, and asterixis.
Laboratory abnormalities may include elevated serum bilirubin, abnormal
aminotransferases, elevated alkaline phosphatase/gamma-glutamyl transpeptidase, a
prolonged prothrombin time/elevated international normalized ratio (INR), hyponatremia,
hypoalbuminemia, and thrombocytopenia.
Symptoms Patients with compensated cirrhosis may be asymptomatic or they may
report nonspecific symptoms, such as anorexia, weight loss, weakness, and fatigue.
Patients with decompensated cirrhosis may present with jaundice, pruritus, signs of
upper gastrointestinal bleeding (hematemesis, melena, hematochezia), abdominal
distension from ascites, or confusion due to hepatic encephalopathy. Patients with
cirrhosis may experience muscle cramps, which can be severe [6-9]. The cause is
incompletely understood, although they may be related to a reduction in effective
circulating plasma volume.
Patients should be asked about fatigue, easy bruisability, lower extremity edema, fever,
weight loss, diarrhea, pruritus, increasing abdominal girth, confusion, or sleep
disturbances (possibly indicating encephalopathy).
In women, chronic anovulation is common, which may manifest as amenorrhea or
irregular menstrual bleeding [10]. Some of the abnormalities may be due to variations in
testosterone, estradiol, prolactin, and luteinizing hormone levels in patients with cirrhosis
compared with normal controls [11].

Men with cirrhosis may develop hypogonadism. It is manifested by impotence, infertility,


loss of sexual drive, and testicular atrophy. It is a feature seen predominantly in patients
with alcoholic cirrhosis and hemochromatosis. More than one mechanism appears to be
involved. In some cases, primary gonadal injury appears to be more prominent, as
suggested by increased serum follicle stimulating hormone (FSH) and luteinizing
hormone (LH) concentrations, whereas in others, suppression of hypothalamic or pituitary
function appears to have a primary role, as suggested by serum LH concentrations that
are not elevated. The toxic effects of alcohol or iron may also contribute to its
development [12]. (See "Causes of primary hypogonadism in males".)
Patients with cirrhosis may also present with a diverse range of signs and symptoms that
reflect the pivotal role that the liver has in the homeostasis of many different bodily
functions. In addition, they may have features related to the underlying cause of cirrhosis
such as cryoglobulinemia from hepatitis C, diabetes mellitus and arthropathy in patients
with hemochromatosis, or extrahepatic autoimmune diseases (such as hemolytic anemia
or thyroiditis) in patients with autoimmune hepatitis.
Physical examination A number of physical findings have been described in patients
with cirrhosis, including jaundice, spider angiomata, gynecomastia, ascites,
splenomegaly, palmar erythema, digital clubbing, and asterixis.
Decreasing blood pressure As cirrhosis progresses, patients often have a decrease in
mean arterial pressure [13]. Patients who were previously hypertensive may become
normotensive or hypotensive. The decrease in mean arterial pressure contributes to the
development of hepatorenal syndrome and is an important predictor of survival. (See
"Hepatorenal syndrome", section on 'Pathogenesis' and "Cirrhosis in adults: Overview of
complications, general management, and prognosis", section on 'Decompensated
cirrhosis'.)
Skin findings Patients with cirrhosis frequently develop jaundice and spider angiomata.
Jaundice is a yellow coloring of the skin and mucus membranes that results from
increased serum bilirubin. It is usually not detectable until the bilirubin is greater than 2
to 3 mg/dL. Hyperbilirubinemia may also cause the urine to appear dark or "cola"
colored. (See "Diagnostic approach to the adult with jaundice or asymptomatic
hyperbilirubinemia".)
Yellow discoloration to the skin can also be caused by excessive consumption of carotene
(such as in patients who consume large quantities of carrots). Yellowing of the skin in
carotenemia can be distinguished from jaundice by the absence of yellow discoloration in
the sclera in the former.
Spider angiomata (also referred to as spider telangiectasias) are vascular lesions
consisting of a central arteriole surrounded by many smaller vessels. They are most
frequently found on the trunk, face, and upper limbs. The body of the lesion (the central
arteriole) can be seen pulsating when compressed with a glass slide. Blood fills the
central arteriole first before traveling to the peripheral tips of each "leg" after blanching.
There are usually multiple radiating legs and surrounding erythema that may encompass
the
entire
lesion
or
only
its
central
portion.
The pathogenesis of spider angiomata is incompletely understood, but they are believed
to result from alterations in sex hormone metabolism. One study suggested that the
presence of spider angiomata in men was associated with an increase in the estradiol to
free testosterone ratio [14]. Acquired spider angiomata are not specific for cirrhosis since
they may also be seen during pregnancy (picture 1) and in patients with severe
malnutrition. They can also be seen in otherwise healthy people, who usually have fewer
than three small lesions. As a general rule, the number and size of spider angiomata
correlate with the severity of liver disease [15,16]. Patients with numerous, large spider
angiomata may be at increased risk for variceal hemorrhage.

Head and neck findings Head and neck findings in patients with cirrhosis may include
parotid gland enlargement and fetor hepaticus. Parotid gland enlargement is typically
seen in patients with alcoholic liver disease and is probably due to alcohol, not cirrhosis
per se. Enlargement is usually secondary to fatty infiltration, fibrosis, and edema rather
than a hyperfunctioning gland [17].
Fetor hepaticus refers to a sweet, pungent smell to the breath of a patient with cirrhosis.
It is caused by increased concentrations of dimethyl sulfide, the presence of which
suggests underlying severe portal-systemic shunting [18].
Chest findings Gynecomastia is seen in up to two-thirds of patients with cirrhosis. It is
possibly caused by increased production of androstenedione from the adrenals,
enhanced aromatization of androstenedione to estrone, and increased conversion of
estrone to estradiol [19]. Men may also develop other features reflecting feminization,
such as loss of chest or axillary hair and inversion of the normal male pubic hair pattern.
Gynecomastia can be seen in a variety of conditions other than cirrhosis. (See
"Epidemiology, pathophysiology, and causes of gynecomastia" and "Clinical features,
diagnosis, and evaluation of gynecomastia".)
Gynecomastia is defined histologically as a benign proliferation of the glandular tissue of
the male breast and clinically by the presence of a rubbery or firm mass extending
concentrically from the nipple(s). Fat deposition without glandular proliferation is termed
pseudogynecomastia (often seen in obese men). These two entities can be distinguished
by having the patient lie on his back with his hands behind his head. The examiner then
places his or her thumb and forefinger on each side of the breast, and slowly brings them
together (figure 1).
Abdominal findings Findings on abdominal examination include hepatomegaly,
splenomegaly, ascites, caput medusae, and a Cruveilhier-Baumgarten murmur.
Ascites Ascites is the accumulation of fluid in the peritoneal cavity. Physical findings in
patients with ascites include abdominal distension, a fluid wave, and flank dullness to
percussion. The accuracy of physical findings is variable, depending in part on the
amount of fluid present, the technique used to examine the patient, and the clinical
setting (eg, detection may be more difficult in patients who are obese). In one study, the
absence of flank dullness was the most accurate predictor against the presence of
ascites; the probability of ascites being present was less than 10 percent in such patients
[20]. However, approximately 1500 mL of fluid had to be present for flank dullness to be
detected. (See "Evaluation of adults with ascites".)
Hepatomegaly The cirrhotic liver may be enlarged, normal sized, or small. While the
presence of a palpable liver may indicate liver disease, a non-palpable liver does not
exclude it. When palpable, the cirrhotic liver has a firm and nodular consistency. The liver
is the largest internal organ in humans and typically spans 21 to 23 cm horizontally and
14 to 17 cm vertically. The size of the normal liver varies depending on sex, height, and
body habitus.
Physical examination of the liver can be helpful for assessing its shape, its consistency,
and whether there is tenderness of the liver edge. It is less useful for assessing its size
since assessment of liver size by physical examination correlates poorly with radiologic
assessment [21]. Nevertheless, the liver span can be estimated using percussion
techniques or the scratch test. The scratch test uses auscultation while lightly scratching
the skin. The intensity of the scratching sound increases when the liver is encountered
with the scratching finger. A normal liver span in the mid-clavicular line by physical
examination is 7 to 10 cm.
In healthy people, the liver is generally not palpable because it lies posterior to the rib
cage. By contrast, an enlarged liver can often be palpated below the costal margin.

However, there are exceptions in which a normal-sized liver can be palpated below the
costal margin including patients with emphysema, a thin-body habitus, the presence of a
hypertrophied caudate lobe (such as seen in patients with Budd-Chiari syndrome), or
Riedel's lobe (an anatomical variant in which there is an extension of the right-lobe
downward and lateral toward the gallbladder). (See "Hepatomegaly: Differential diagnosis
and evaluation".)
Splenomegaly Splenomegaly is common, especially in patients with cirrhosis from
nonalcoholic etiologies [22]. It is believed to be caused primarily by congestion of the red
pulp resulting from portal hypertension. However, splenic size does not correlate well
with portal pressures, suggesting that other factors may be contributing [23]. The
differential diagnosis of splenomegaly includes several other disorders. (See "Approach
to the adult patient with splenomegaly and other splenic disorders".)
Caput medusae The veins of the lower abdominal wall normally drain inferiorly into the
iliofemoral system, while the veins of the upper abdominal wall drain superiorly into the
veins of the thoracic wall and axilla. When portal hypertension occurs as the result of
cirrhosis, the umbilical vein, normally obliterated in early life, may open. Blood from the
portal venous system may be shunted through the periumbilical veins into the umbilical
vein and ultimately to the abdominal wall veins, causing them to become prominent. This
appearance has been said to resemble the head (caput) of the mythical Gorgon Medusa.
Dilated abdominal veins can also be seen in the inferior vena cava syndrome [24] and
the superior vena cava syndrome (if obstruction includes the azygous system) [25]. In
these conditions, collateral veins tend to be more prominent in the lateral aspect of the
abdominal wall. One maneuver that has been proposed to distinguish vena caval
obstruction from portal hypertension is to pass a finger along dilated veins located
below the umbilicus to strip them of blood and determine the direction of blood flow
during refilling. In portal-systemic collateral veins, the blood flow should be directed
inferiorly, away from the umbilicus, whereas vena caval collateral vein flow should be
cephalad. However, the actual ability of this maneuver to discriminate between the two
is poor, since in both conditions the dilated veins may lack valves and thus have
bidirectional blood flow [26].
Cruveilhier-Baumgarten murmur The Cruveilhier-Baumgarten murmur is a venous hum
that may be auscultated in patients with portal hypertension. It results from collateral
connections between the portal system and the remnant of the umbilical vein. It is best
appreciated when the stethoscope is placed over the epigastrium. The murmur is
augmented by maneuvers that increase intraabdominal pressure, such as the Valsalva
maneuver, and diminished by applying pressure on the skin above the umbilicus [27].
Genitourinary findings Men with cirrhosis may have testicular atrophy due to the
development of hypogonadism. (See 'Symptoms' above.)
Extremity findings Findings on examination of the extremities of a patient with
cirrhosis may include palmar erythema, nail changes, clubbing, hypertrophic
osteoarthropathy, and Dupuytren's contracture.
Palmar erythema is an exaggeration of the normal speckled mottling of the palm and is
believed to be caused by altered sex hormone metabolism [23]. It is most frequently
found on the thenar and hypothenar eminences, while sparing the central portions of the
palm. Palmar erythema is not specific for liver disease and can be seen in association
with pregnancy, rheumatoid arthritis, hyperthyroidism, and hematological malignancies.
Nail changes include Muehrcke nails and Terry nails. Muehrcke nails are paired horizontal
white bands separated by normal color. The exact pathogenesis is unknown, but it is
believed to be caused by hypoalbuminemia [28]. They are not specific for cirrhosis since
they may also be seen in other conditions associated with a low serum albumin, such as

the nephrotic syndrome. In patients with Terry nails, the proximal two-thirds of the nail
plate appears white, whereas the distal one-third is red (picture 2). This finding is also
believed to be secondary to a low serum albumin [28].
Clubbing and hypertrophic osteoarthropathy are two additional findings in patients with
cirrhosis. Clubbing is present when the angle between the nail plate and proximal nail
fold is greater than 180 degrees (figure 2). When severe, the distal finger has a "drum
stick" appearance. Hypertrophic osteoarthropathy (HOA) is a chronic proliferative
periostitis of the long bones that can cause considerable pain. Clubbing is more common
in biliary causes of cirrhosis (particularly primary biliary cirrhosis), while hypertrophic
osteoarthropathy can be seen with various causes of liver disease [29,30]. Neither
feature is specific for liver disease. The pathogenesis of clubbing and hypertrophic
osteoarthropathy is not well understood. The most frequent cause of hypertrophic
osteoarthropathy is lung cancer, which should be sought in the appropriate setting. (See
"Overview of nail disorders", section on 'Clubbing' and "Malignancy and rheumatic
disorders", section on 'Hypertrophic osteoarthropathy'.)
Dupuytren's contracture results from the thickening and shortening of the palmar fascia,
which causes flexion deformities of the fingers (picture 3). Pathologically, it is
characterized by fibroblastic proliferation and disorderly collagen deposition with fascial
thickening. The pathogenesis is unknown but may be related to free radical formation
generated by the oxidative metabolism of hypoxanthine [31]. It is relatively common in
patients with alcoholic cirrhosis, in whom it may be found in as many as a third of
patients [32]. However, it can also be seen in several other conditions, including in
workers exposed to repetitive handling tasks or vibration, and patients with diabetes
mellitus, reflex sympathetic dystrophy, cigarette smoking and alcohol consumption, and
Peyronie's disease. (See "Dupuytren's contracture".)
Neurologic findings Asterixis (bilateral but asynchronous flapping motions of
outstretched, dorsiflexed hands) is seen in patients with hepatic encephalopathy.
Asterixis may also be seen in patients with uremia and severe heart failure. (See "Hepatic
encephalopathy in adults: Clinical manifestations and diagnosis".)
Laboratory findings Several laboratory abnormalities may be seen in patients with
cirrhosis. In addition, because it is common for panels of serum chemistries to be sent for
screening or evaluation of specific complaints, laboratory abnormalities may be the first
indication that a patient has cirrhosis. Common abnormalities include elevated serum
bilirubin, abnormal aminotransferases, elevated alkaline phosphatase/gamma-glutamyl
transpeptidase, a prolonged prothrombin time/elevated international normalized ratio
(INR), hyponatremia, and thrombocytopenia. (See "Approach to the patient with
abnormal liver biochemical and function tests".)
Liver function tests Although the term "liver function tests" (LFTs) is commonly used, it
is imprecise since many of the tests reflecting the health of the liver are not direct
measures of its function. The most common laboratory measures classified as LFTs
include the enzyme tests (principally the serum aminotransferases, alkaline
phosphatase, and gamma-glutamyl transpeptidase), the serum bilirubin, and tests of
synthetic function (principally the serum albumin concentration and prothrombin time).
Aminotransferases Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) are usually moderately elevated in patients with cirrhosis. AST is more often
elevated than ALT. However, normal aminotransferases do not preclude a diagnosis of
cirrhosis [33]. Most forms of chronic hepatitis other than alcoholic liver disease have a
ratio of AST/ALT less than one. However, as chronic hepatitis progresses to cirrhosis, the
ratio of AST to ALT may reverse [34,35]. (See "Approach to the patient with abnormal
liver biochemical and function tests", section on 'AST to ALT ratio'.)

Alkaline phosphatase Alkaline phosphatase is usually elevated in the setting of


cirrhosis but is less than two to three times the upper normal limit. Higher levels may be
seen in patients with underlying cholestatic liver disease, such as primary sclerosing
cholangitis or primary biliary cirrhosis. (See "Enzymatic measures of cholestasis (eg,
alkaline phosphatase, 5-nucleotidase, gamma-glutamyl transpeptidase)".)
Gamma-glutamyl transpeptidase Gamma-glutamyl transpeptidase (GGT) levels
correlate reasonably well with alkaline phosphatase in liver disease but are nonspecific
[36]. Levels of GGT are typically much higher in chronic liver disease from alcohol than
other causes. This may be the result of alcohol inducing hepatic microsomal GGT [37] or
alcohol causing GGT to leak from hepatocytes [38]. (See "Enzymatic measures of
cholestasis
(eg,
alkaline
phosphatase,
5-nucleotidase,
gamma-glutamyl
transpeptidase)".)
Bilirubin Bilirubin levels may be normal in well-compensated cirrhosis. However, they
rise as the cirrhosis progresses. In patients with primary biliary cirrhosis, a rising serum
bilirubin portends a poor prognosis [39]. (See "Clinical aspects of serum bilirubin
determination".)
Albumin Albumin is synthesized exclusively in the liver. Albumin levels fall as the
synthetic function of the liver declines with worsening cirrhosis. Thus, serum albumin
levels can be used to help grade the severity of cirrhosis. Hypoalbuminemia is not
specific for liver disease, since it may be seen in many other medical conditions such as
heart failure, the nephrotic syndrome, protein losing enteropathy, or malnutrition. (See
"Tests of the liver's biosynthetic capacity (eg, albumin, coagulation factors, prothrombin
time)".)
Prothrombin time Most of the proteins involved in the coagulation process are
produced in the liver. Thus, the prothrombin time reflects the degree of hepatic synthetic
dysfunction. The prothrombin time increases as the ability of a cirrhotic liver to
synthesize clotting factors diminishes. Thus, worsening coagulopathy correlates with the
severity of hepatic dysfunction. (See "Tests of the liver's biosynthetic capacity (eg,
albumin, coagulation factors, prothrombin time)".)
Other liver function tests The ability of the liver to transport organic anions and
metabolize drugs has led to the development of a multitude of tests to assess the
function of the liver. None is used routinely in clinical practice. (See "Tests of the liver's
capacity to transport organic anions and metabolize drugs".)
Serum chemistries Hyponatremia is common in patients with cirrhosis and ascites and
is related to an inability to excrete free water. This results primarily from high levels of
anti-diuretic hormone secretion [40]. Hyponatremia often becomes severe as cirrhosis
progresses to end-stage liver disease [41]. (See "Hyponatremia in patients with
cirrhosis".)
As cirrhosis progresses, patients may develop hepatorenal syndrome, with a progressive
rise in serum creatinine. (See "Hepatorenal syndrome".)
Hematologic abnormalities Patients with cirrhosis commonly have a number of
hematologic abnormalities, including varying degrees of cytopenia. Thrombocytopenia is
the most common hematologic abnormality, while leukopenia and anemia develop later
in the disease course [42].
Thrombocytopenia is mainly caused by portal hypertension with attendant congestive
splenomegaly. An enlarged spleen can result in temporary sequestration of up to 90
percent of the circulating platelet mass. However, this uncommonly results in platelet
counts less than 50,000/mL, and unless complicated by coexisting coagulopathy, it is
rarely a clinical problem [36]. Decreased thrombopoietin levels may also contribute to

thrombocytopenia. (See "Clinical applications of thrombopoietic growth factors" and


"Coagulation abnormalities in patients with liver disease", section on 'Abnormalities of
platelet number and function'.)
Anemia is usually multifactorial in origin; acute and chronic gastrointestinal blood loss,
folate deficiency, direct toxicity due to alcohol, hypersplenism, bone marrow suppression
(as in hepatitis-associated aplastic anemia), the anemia of chronic disease
(inflammation), and hemolysis may all contribute. (See "Approach to the adult patient
with anemia".)
Leukopenia and neutropenia are due to hypersplenism with splenic margination.
Other abnormalities Globulins tend to be increased in patients with cirrhosis. This may
be secondary to shunting of bacterial antigens in portal venous blood away from the liver
to lymphoid tissue, which induces immunoglobulin production [43]. Marked elevations of
IgG may be a clue to the presence of autoimmune hepatitis. Increased levels of IgM are
present in 90 to 95 percent of patients with primary biliary cirrhosis.
In addition to deficiency of coagulant proteins, patients may develop varying degrees of
disseminated intravascular coagulation, fibrinolysis, vitamin K deficiency, and
dysfibrinogenemia, all of which may contribute to bleeding. (See "Coagulation
abnormalities in patients with liver disease".)
Patients often have laboratory findings related to diabetes mellitus. Diabetes mellitus is
seen in 15 to 30 percent of patients with cirrhosis [44]. Insulin resistance is present in
many patients with nonalcoholic fatty liver disease. Diabetes may also be common in
patients with chronic hepatitis C. The pathogenesis is likely related to insulin resistance
and an inadequate secretion of insulin from the beta cells of the pancreas [45]. Diabetes
may also be seen in patients with hemochromatosis. (See "Extrahepatic manifestations
of hepatitis C virus infection", section on 'Diabetes mellitus' and "Clinical manifestations
of hereditary hemochromatosis", section on 'Diabetes mellitus' and "Epidemiology,
clinical features, and diagnosis of nonalcoholic fatty liver disease in adults", section on
'Association with other disorders'.)
Radiologic findings Radiologic studies such as abdominal ultrasound, computed
tomography scan, and magnetic resonance imaging may suggest the presence of
cirrhosis. Findings may include a liver that appears shrunken, irregular, and nodular.
Imaging studies may also show evidence of varices and ascites in patients with portal
hypertension. (See 'Imaging studies' below.)
DIAGNOSIS In patients suspected of having cirrhosis, abdominal imaging (typically
ultrasound) is obtained to evaluate the liver parenchyma and to detect extrahepatic
manifestations of cirrhosis. A liver biopsy is required to definitively confirm the diagnosis.
However, it is generally not necessary if the clinical, laboratory, and radiologic data
strongly suggest the presence of cirrhosis and the results would not alter the patient's
management. Noninvasive serologic and radiographic methods for diagnosing cirrhosis
are also being developed. (See "Noninvasive assessment of hepatic fibrosis: Overview of
serologic and radiographic tests".)
When to suspect cirrhosis Cirrhosis is often suspected in patients with [46]:
Stigmata of chronic liver disease discovered on physical examination (table 1) (see
'Physical examination' above)
Evidence of cirrhosis on laboratory or radiologic testing or by direct visualization while
undergoing a surgical procedure

Evidence of decompensated cirrhosis, which is characterized by the presence of


dramatic and life-threatening complications, such as variceal hemorrhage, ascites,
spontaneous bacterial peritonitis, or hepatic encephalopathy
A meta-analysis found that the factors with the best ability to predict cirrhosis in adults
with known or suspected liver disease included [47]:
Presence of ascites (likelihood ratio [LR] 7.2)
Platelet count <160,000/mm3 (LR 6.3)
Spider angiomata (LR 4.3)
Bonacini cirrhosis discriminant score greater than 7 (LR 9.4)
The Bonacini cirrhosis discriminant score is calculated by giving points for the following
parameters [48]:
Platelets (x1000/mm3):
>340 zero points
280 to 399 one point
220 to 279 two points
160 to 219 three points
100 to 159 four points
40 to 99 five points
<40 six points
Alanine aminotransferase to aspartate aminotransferase (ALT/AST) ratio:
>1.7 zero points
1.2 to 1.7 one point
0.6 to 1.19 two points
<0.6 three points
International normalized ratio (INR):
<1.1 zero points
1.1 to 1.4 one point
>1.4 two points
Factors associated with a low likelihood of cirrhosis included:

Lok index <20 percent (LR 0.09)


Platelet count of 160,000/mm3 or higher (LR 0.29)
Absence of hepatomegaly (LR 0.37)
The Lok index is calculated using the platelet count, AST, ALT, and INR [49]. An online
calculator is available. In a validation study, when a cutoff of <20 percent was used to
exclude cirrhosis, the test had a specificity of 92 percent. When a cutoff of >50 percent
was used to diagnose cirrhosis, the test had a sensitivity of 85 percent. Of note, the Lok
index has only been validated in patients with hepatitis C virus.
Laboratory tests Several noninvasive tests for the diagnosis of cirrhosis have been
proposed, but none has yet emerged as a standard. Examples include the AST to platelet
ratio index and FibroTest/FibroSure. Nevertheless, they can provide adjunctive
information to conventional laboratory testing. (See "Noninvasive assessment of hepatic
fibrosis: Overview of serologic and radiographic tests".)
Imaging studies Abdominal imaging is typically obtained in patients suspected of
having cirrhosis, though radiographic imaging alone is not adequately sensitive or
specific to diagnose cirrhosis. The findings must be viewed in light of other signs of
cirrhosis, such as physical examination or laboratory test findings. In addition to
evaluating the liver, abdominal imaging may reveal hepatocellular carcinoma or
extrahepatic findings suggestive of cirrhosis, such as ascites, varices, splenomegaly, and
hepatic or portal vein thrombosis. Abdominal ultrasound is typically the first radiologic
study obtained because it is readily available, provides information about the appearance
of the liver and blood flow within the portal circulation, is less expensive than other
imaging modalities, and does not expose patients to intravenous contrast or radiation.
In rare instances, radiographic findings suggest the etiology of cirrhosis. A hypertrophied
caudate lobe discovered on CT scanning, for example, suggests Budd-Chiari syndrome
[50]. Decreased signal intensity on magnetic resonance imaging may indicate iron
overload from hereditary hemochromatosis (image 1) [51].
Ultrasonography Ultrasonography is routinely used during the evaluation of
cirrhosis. It is noninvasive, well-tolerated, widely available, and provides valuable
information. In advanced cirrhosis, the liver may appear small and nodular. Surface
nodularity and increased echogenicity with irregular appearing areas are consistent with
cirrhosis, but can also be seen with hepatic steatosis [52,53]. There is typically atrophy of
the right lobe and hypertrophy of the caudate or left lobes. Investigators have attempted
to use the ratio of the width of the caudate lobe to the width of the right lobe as an
ultrasonographic criterion for the diagnosis of cirrhosis. However, the sensitivity is poor
[54].
In one study of high-resolution ultrasonography in patients suspected of having cirrhosis
who underwent liver biopsy, ultrasonography had a sensitivity of 91 percent and a
specificity of 94 percent for making the diagnosis [55].
Ultrasonography may also be used as a screening test for hepatocellular carcinoma and
portal hypertension. The finding of nodules on ultrasonography warrants further
evaluation since benign and malignant nodules can have similar ultrasonographic
appearances. Findings of portal hypertension include an increased diameter of the portal
vein, the presence of collateral veins, and decreased flow within the portal circulation on
Doppler imaging [2,56]. Ultrasonography is also useful for detecting splenomegaly,
ascites, and portal vein thrombosis. (See "Clinical features and diagnosis of primary
hepatocellular carcinoma", section on 'Ultrasound' and "Solid liver lesions: Differential
diagnosis and evaluation", section on 'Patients with cirrhosis or chronic hepatitis B virus
infection'.)

Computed tomography Computed tomography (CT) is not routinely used in the


diagnosis and evaluation of cirrhosis. It provides similar information to ultrasonography,
but at the expense of radiation and contrast exposure. CT findings of hepatic nodularity,
atrophy of the right lobe and hypertrophy of the caudate or left lobes, ascites, or varices
suggest the presence of cirrhosis, but they are not diagnostic. Patency of the portal vein
can be demonstrated with CT portal phase imaging, but the direction of blood flow
cannot be determined.
Magnetic resonance imaging The role of magnetic resonance imaging (MRI) in the
diagnosis of cirrhosis is unclear. Despite much enthusiasm about the potential of MRI in
the evaluation of patients with cirrhosis, its use is limited by expense, poor tolerance of
the examination by some patients, and the ability to obtain information provided by MRI
through other means.
Some authors report that MRI can accurately diagnose cirrhosis and provide correlation
with its severity [57-59]. One study found the sensitivity and specificity of an MRI scoring
system in distinguishing Child-Pugh grade A cirrhosis from other grades to be 93 and 82
percent, respectively [57]. MRI may also reveal iron overload and provide an estimate of
the hepatic iron concentration [51,60,61]. Magnetic resonance angiography (MRA) is
more sensitive than ultrasonography for diagnosing complications of cirrhosis, such as
portal vein thrombosis [62]. Unlike CT portal phase imaging, MRA can determine the
volume and direction of blood flow in the portal vein.
Elastography Increasing scarring of the liver is associated with increasing "stiffness"
of the tissue. Several methods have been developed to assess liver stiffness. (See
"Noninvasive assessment of hepatic fibrosis: Overview of serologic and radiographic
tests", section on 'Radiologic tests'.)
Nuclear studies Radionuclide testing can be useful in suggesting the diagnosis of
cirrhosis [63]. 99mTc sulfur colloid is normally taken up by cells of the reticuloendothelial
system. In patients with cirrhosis, there may be heterogeneity in the uptake of 99mTc
sulfur colloid by the liver and increased uptake by the spleen and bone marrow. The
exact sensitivity and specificity of these findings in making the diagnosis of cirrhosis is
unknown. Given the widespread use of other imaging modalities, this test is seldom
performed in clinical practice.
Liver biopsy The gold standard for diagnosing cirrhosis is examination of an explanted
liver, either at autopsy or following liver transplantation, because the architecture of the
entire liver can be appreciated. In clinical practice, cirrhosis is diagnosed with a liver
biopsy (picture 4), during which a sample of the liver is obtained by either a
percutaneous, transjugular, laparoscopic, or radiographically-guided fine-needle
approach. The method for obtaining the biopsy will depend on the clinical setting [64].
The sensitivity of a liver biopsy for cirrhosis is in the range of 80 to 100 percent,
depending on the method used, and the size and number of specimens obtained. (See
"Percutaneous, fine-needle aspiration, and laparoscopic liver biopsy" and "Transjugular
liver biopsy".)
However, liver biopsy is not necessary if the clinical, laboratory, and radiologic data
strongly suggest the presence of cirrhosis and if the results would not alter the patient's
management. An example would be a patient with a history of heavy alcohol use who
has ascites, severe coagulopathy, and a shrunken, nodular-appearing liver on
ultrasonography.
In addition to demonstrating that cirrhosis is present, a liver biopsy can sometimes
suggest the cause. This is especially true for metabolic causes of cirrhosis, such as
hereditary hemochromatosis (picture 5), nonalcoholic steatohepatitis (picture 6), Wilson
disease (picture 7), and alpha-1 antitrypsin deficiency. (See "Pathophysiology and
diagnosis of hereditary hemochromatosis and other iron overload syndromes", section on

'Liver biopsy' and "Epidemiology, clinical features, and diagnosis of nonalcoholic fatty
liver disease in adults", section on 'Role of liver biopsy' and "Wilson disease: Diagnostic
tests", section on 'Liver biopsy'.)
DETERMINING THE CAUSE OF CIRRHOSIS Many causes of chronic liver injury can lead
to cirrhosis (table 2), and a specific etiology can be determined in 85 to 90 percent of
patients [65]. Determining the etiology of cirrhosis is important because it may influence
treatment decisions, permit counseling of family members, and help predict the patient's
prognosis. The initial evaluation includes obtaining a history, performing a physical
examination, and obtaining routine blood tests (ie, liver biochemical and function tests
and a complete blood count). The findings from the initial evaluation are then used to
guide additional testing. (See "Approach to the patient with abnormal liver biochemical
and function tests", section on 'Initial evaluation'.)
If the initial evaluation does not help guide the evaluation (eg, in a patient with an
unremarkable history and normal laboratory tests), testing for common causes of
cirrhosis should be performed. An overview of the approach to determining the cause of a
patient's liver disease is discussed in detail elsewhere. In addition, detailed discussions of
the diagnosis of specific disorders can be found in their respective topic reviews. (See
'Etiologies and classification' above and "Approach to the patient with abnormal liver
biochemical and function tests".)
WHEN TO REFER TO A SPECIALIST Referral to a hepatologist should be considered in
patients suspected of having cirrhosis if the diagnosis remains unclear after noninvasive
testing (eg, imaging and laboratory tests). In particular, referral should be considered
prior to obtaining a liver biopsy. It is also reasonable to refer to a specialist to aid with
determining the cause of the cirrhosis if common etiologies are ruled out (eg, hepatitis C)
or to aid with management. (See "Cirrhosis in adults: Overview of complications, general
management, and prognosis", section on 'When to refer to a specialist'.)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials,
"The Basics" and "Beyond the Basics." The Basics patient education pieces are written in
plain language, at the 5th to 6th grade reading level, and they answer the four or five key
questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10 th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on "patient info" and the keyword(s) of
interest.)
Basics topics (see "Patient information: Cirrhosis (The Basics)")
Beyond the Basics topics (see "Patient information: Cirrhosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
There are numerous causes of liver disease that can result in cirrhosis, either by
causing chronic hepatic inflammation or cholestasis (table 2). The two most common
causes of cirrhosis in the United States are alcoholic liver disease and hepatitis C, which
together accounted for approximately one-half of patients on the liver transplantation
wait list in 2011. (See 'Etiologies and classification' above.)

The clinical manifestations of cirrhosis may include nonspecific symptoms (eg,


anorexia, weight loss, weakness, fatigue) or signs and symptoms of hepatic
decompensation (jaundice, pruritus, signs upper gastrointestinal bleeding, abdominal
distension from ascites, confusion due to hepatic encephalopathy) (table 1). Physical
examination findings may include jaundice, spider angiomata, gynecomastia, ascites,
splenomegaly, palmar erythema, digital clubbing, and asterixis. Laboratory abnormalities
may include elevated serum bilirubin, abnormal aminotransferases, elevated alkaline
phosphatase/gamma-glutamyl transpeptidase, a prolonged prothrombin time/elevated
international normalized ratio (INR), hyponatremia, and thrombocytopenia. (See
'Laboratory findings' above.)
Cirrhosis is often suspected in patients with (see 'When to suspect cirrhosis' above):
Stigmata of chronic liver disease discovered on physical examination (see 'Physical
examination' above)
Evidence of cirrhosis on laboratory or radiologic testing or by direct visualization while
undergoing a surgical procedure
Evidence of decompensated cirrhosis, which is characterized by the presence of
dramatic and life-threatening complications, such as variceal hemorrhage, ascites,
spontaneous bacterial peritonitis, or hepatic encephalopathy
In patients suspected of having cirrhosis, abdominal imaging is typically obtained,
though radiographic imaging alone is not adequately sensitive or specific to diagnose
cirrhosis. The findings must be viewed in light of other signs of cirrhosis, such as physical
examination or laboratory test findings. In addition to evaluating the liver, abdominal
imaging may reveal hepatocellular carcinoma or extrahepatic findings suggestive of
cirrhosis, such as ascites, varices, splenomegaly, and hepatic or portal vein thrombosis.
(See 'Imaging studies' above.)
Abdominal ultrasound is typically the first radiologic study obtained because it is readily
available, provides information about the appearance of the liver and blood flow within
the portal circulation, is less expensive than other imaging modalities, and does not
expose patients to intravenous contrast or radiation. (See 'Imaging studies' above.)
A liver biopsy is required to definitively confirm the diagnosis of cirrhosis. However, it is
generally not necessary if the clinical, laboratory, and radiologic data strongly suggest
the presence of cirrhosis and the results would not alter the patient's management. (See
'Liver biopsy' above.)
Noninvasive serologic and radiographic methods for diagnosing cirrhosis are also being
developed. (See "Noninvasive assessment of hepatic fibrosis: Overview of serologic and
radiographic tests".)
A specific etiology can be determined in 85 to 90 percent of patients with cirrhosis.
Determining the etiology of cirrhosis is important because it may influence treatment
decisions, permit counseling of family members, and help predict the patient's prognosis.
The initial evaluation includes obtaining a history, performing a physical examination,
and obtaining routine blood tests (ie, liver biochemical and function tests and a complete
blood count). The findings from the initial evaluation are then used to guide additional
testing. (See "Approach to the patient with abnormal liver biochemical and function
tests", section on 'Initial evaluation'.)
MAJOR COMPLICATIONS Major complications of cirrhosis include (table 1):
Variceal hemorrhage

Ascites
Spontaneous bacterial peritonitis
Hepatic encephalopathy
Hepatocellular carcinoma
Hepatorenal syndrome
Hepatopulmonary syndrome
Once these complications develop, patients are considered to have decompensated
cirrhosis. Multiple factors can predispose to decompensation in a patient with cirrhosis.
Risk factors for decompensation include bleeding, infection, alcohol intake, medications,
dehydration, and constipation [3-5]. In addition, patients with obesity are at increased
risk for decompensation [6]. Once decompensation has developed, patients should be
considered for liver transplantation. (See "Liver transplantation in adults: Patient
selection and pretransplantation evaluation" and "Liver transplantation in adults: Patient
selection and pretransplantation evaluation", section on 'Cirrhosis'.)
Other major complications of cirrhosis include portal vein thrombosis and
cardiomyopathy. However, patients with these complications alone are not considered to
have decompensated cirrhosis.
This section provides an overview of the complications of cirrhosis. The individual
complications are discussed in detail in their respective topic reviews.
Complications of portal hypertension Many of the complications of cirrhosis are the
result of portal hypertension (increased pressure within the portal venous system). This
can lead to the formation of venous collaterals (varices) as well as circulatory, vascular,
functional, and biochemical abnormalities that contribute to the pathogenesis of ascites
and other complications. (See "Portal hypertension in adults" and "Pathogenesis of
ascites in patients with cirrhosis", section on 'Portal hypertension'.)
Complications of portal hypertension include:
Ascites
Hepatic encephalopathy
Variceal hemorrhage
Spontaneous bacterial peritonitis
Hepatorenal syndrome
Portal hypertensive gastropathy
Hepatic hydrothorax
Hepatopulmonary syndrome
Portopulmonary hypertension

Cirrhotic cardiomyopathy
Variceal hemorrhage Patients with variceal hemorrhage typically present with
hematemesis and/or melena. It is typically treated with endoscopic variceal band
ligation. Other treatments include endoscopic sclerotherapy and placement of a
transjugular intrahepatic portosystemic shunt (TIPS). (See "General principles of the
management of variceal hemorrhage".)
Variceal hemorrhage is associated with high mortality rates. In the past, the mortality
rate of a single variceal hemorrhage was 30 percent, and only one-third of patients
survived for one year [7,8]. Although survival has improved with modern techniques for
controlling variceal hemorrhage, mortality rates remain high (15 to 20 percent 30-day
mortality) [9].
Portal hypertensive gastropathy Portal hypertensive gastropathy (congestive
gastropathy), while extremely common in patients with portal hypertension, is an
uncommon cause of significant bleeding in these patients. When portal hypertensive
gastropathy is the sole cause of bleeding, there is diffuse mucosal oozing with no other
lesions, such as varices, to account for the GI bleeding and anemia. The mucosa is
friable, and bleeding presumably occurs when the ectatic vessels rupture. The severity of
gastropathy is related to the level of portal pressure, the level of hepatic vascular
resistance, and the degree of reduction in hepatic blood flow (See "Uncommon causes of
upper gastrointestinal bleeding in adults", section on 'Portal hypertensive gastropathy'.)
Ascites Ascites is the accumulation of fluid within the peritoneal cavity. It is the most
common complication of cirrhosis. The first step leading to fluid retention and ultimately
ascites in patients with cirrhosis is the development of portal hypertension. Patients
without portal hypertension do not develop ascites or edema. Those with ascites have
several circulatory, vascular, functional, and biochemical abnormalities that contribute to
the pathogenesis of fluid retention. (See "Pathogenesis of ascites in patients with
cirrhosis".)
Ascites is typically treated with a combination of diuretics and sodium restriction, though
some patients require repeated therapeutic paracenteses or TIPS placement. Among
patients with refractory ascites or spontaneous bacterial peritonitis, the use of
nonselective beta blockers may be associated with increased mortality [10,11]. This may
occur because failure to maintain an adequate mean arterial blood pressure is strongly
correlated with survival in patients with advanced cirrhosis. (See "Ascites in adults with
cirrhosis: Initial therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites",
section on 'Discontinuing beta blockers' and 'Decompensated cirrhosis' below and
"Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on
'Discontinue nonselective beta blockers'.)
Spontaneous bacterial peritonitis Spontaneous bacterial peritonitis (SBP) is an
infection of preexisting ascitic fluid without evidence for an intra-abdominal secondary
source, such as a perforated viscus. SBP is almost always seen in the setting of end-stage
liver disease. Clinical manifestations of SBP include fever, abdominal pain, abdominal
tenderness, and altered mental status. Some patients are asymptomatic and present
with only mild laboratory abnormalities. (See "Spontaneous bacterial peritonitis in adults:
Clinical manifestations".)
The index of suspicion for SBP must be high with a low threshold for diagnostic
paracentesis. The diagnosis is established by a positive ascitic fluid bacterial culture
and/or an elevated ascitic fluid absolute polymorphonuclear leukocyte count (250
cells/mm3). Without early antibiotic treatment, mortality is high. (See "Spontaneous
bacterial peritonitis in adults: Diagnosis" and "Spontaneous bacterial peritonitis in adults:
Treatment and prophylaxis".)

Hepatorenal syndrome Hepatorenal syndrome refers to the development of renal


failure in a patient who has advanced liver disease due to cirrhosis, severe alcoholic
hepatitis, acute liver failure, or less often, a metastatic tumor. Rather than being a new
disease, hepatorenal syndrome usually represents the end-stage of a sequence of
reductions in renal perfusion induced by increasingly severe hepatic injury. Arterial
vasodilatation in the splanchnic circulation, which is triggered by portal hypertension,
appears to play a central role in the hemodynamic changes and the decline in renal
function in hepatorenal syndrome. The initial reductions in glomerular filtration rate are
often masked clinically since associated decreases in muscle mass and hepatic urea
production minimize elevations in the plasma creatinine concentration and blood urea
nitrogen. (See "Hepatorenal syndrome", section on 'Pathogenesis'.)
Hepatorenal syndrome is characterized by a generally benign urine sediment, a very low
rate of sodium excretion, and a progressive rise in the plasma creatinine concentration.
There is some confusion regarding the presence or absence of oliguria. The percentage of
patients with oliguria depends upon the cut-off for defining oliguria. If the cut-off is 400
mL/day, only 44 percent of patients are oliguric. If 500 mL/day is used, about two-thirds
are oliguric. (See "Hepatorenal syndrome", section on 'Clinical presentation'.)
The diagnosis is one of exclusion, being made when other causes of renal dysfunction
have been excluded. In particular, volume depletion (as with overly-rapid diuresis) can
mimic all of the findings of hepatorenal syndrome. The prognosis is poor unless hepatic
function improves or a liver transplantation is performed. (See "Hepatorenal syndrome",
section on 'Diagnosis' and "Hepatorenal syndrome", section on 'Treatment'.)
Hepatic hydrothorax Hepatic hydrothorax is defined as the presence of a pleural
effusion in a patient with cirrhosis and no evidence of underlying cardiopulmonary
disease. It results from the movement of ascitic fluid into the pleural space through
defects in the diaphragm, and it is usually right-sided. (See "Hepatic hydrothorax".)
The treatment for hepatic hydrothorax includes diuretics and sodium restriction. Patients
who do not respond to conservative therapy may require repeated therapeutic
thoracenteses or TIPS. The most important aspect of management is evaluation for liver
transplantation (algorithm 1). Chest tubes should not be placed in patients with hepatic
hydrothorax. Placement of chest tubes in this setting can result in massive protein and
electrolyte depletion, infection, renal failure, and bleeding.
Hepatopulmonary syndrome Hepatopulmonary syndrome (HPS) is defined by the
following triad (see "Hepatopulmonary syndrome: Prevalence, causes, clinical
manifestations, and diagnosis"):
Liver disease
Increased alveolar-arterial gradient while breathing room air
Evidence for intrapulmonary vascular abnormalities, referred to as intrapulmonary
vascular dilatations
Estimates of the prevalence of HPS among patients with chronic liver disease range from
4 to 47 percent, depending on the diagnostic criteria and methods used. Even in those
without HPS, mild hypoxemia is common and is presumably caused by ascites, with
resulting diaphragmatic elevation and ventilation/perfusion mismatch. There are no
effective medical therapies for HPS. Liver transplantation offers the most promise for
successful treatment. (See "Hepatopulmonary syndrome: Natural history, treatment, and
outcomes".)

Portopulmonary hypertension Portal hypertension-associated pulmonary hypertension


(portopulmonary hypertension) refers to the presence of pulmonary hypertension in
patients with portal hypertension. The prevalence in patients with cirrhosis is
approximately 2 percent [12]. Neither the prevalence nor the severity of portopulmonary
hypertension appears to correlate with the degree of portal hypertension [12]. (See
"Portopulmonary hypertension".)
Patients with portopulmonary hypertension may present with fatigue, dyspnea,
peripheral edema, chest pain, and syncope. The diagnosis may be suggested by
echocardiography and confirmed by right heart catheterization. Patients with moderate
to severe portopulmonary hypertension are difficult to treat with medical therapy, and
the perioperative mortality with liver transplantation is high.
Cirrhotic cardiomyopathy Up To 50 percent of patients with advanced cirrhosis have
features of cardiac dysfunction. The term "cirrhotic cardiomyopathy" has been used to
describe such patients, who are characterized as having normal to increased cardiac
output and contractility at rest, but a blunted response to pharmacologic, physiologic, or
pathologic stress [13]. Patients may also have electrophysiologic abnormalities. It is
thought to be related to both portal hypertension and cirrhosis. Cardiomyopathy can
occur from any cause of cirrhosis, although patients with alcoholism or hemochromatosis
may have additional contributing causes to cardiac dysfunction. (See "High-output heart
failure", section on 'Cirrhosis' and "Definition and classification of the cardiomyopathies",
section on 'Cirrhotic cardiomyopathy'.)
Hepatic encephalopathy Hepatic encephalopathy describes the spectrum of potentially
reversible neuropsychiatric abnormalities seen in patients with liver dysfunction.
Disturbance in the diurnal sleep pattern (insomnia and hypersomnia) is a common early
feature that typically precedes overt neurologic signs (figure 1 and figure 2). More
advanced neurologic features include the presence of asterixis, hyperactive deep tendon
reflexes, and, less commonly, transient decerebrate posturing. (See "Hepatic
encephalopathy in adults: Clinical manifestations and diagnosis".)
Treatments for hepatic encephalopathy include addressing any predisposing conditions
(eg, infection or gastrointestinal bleeding), synthetic disaccharides (eg, lactulose), and
nonabsorbable antibiotics (eg, rifaximin). (See "Hepatic encephalopathy in adults:
Treatment".)
Hepatocellular carcinoma Patients with cirrhosis have a markedly increased risk of
developing hepatocellular carcinoma (HCC). Patients with most forms of chronic hepatitis
are not at an increased risk until cirrhosis develops. Exceptions to this rule are patients
with chronic hepatitis B virus infection, who can develop HCC in the absence of cirrhosis.
(See "Epidemiology and etiologic associations of hepatocellular carcinoma" and
"Prevention of hepatocellular carcinoma and recommendations for surveillance in adults
with chronic liver disease".)
Certain causes of cirrhosis appear to have a relatively increased risk for HCC. Patients
with cirrhosis from hepatitis B, hepatitis C, nonalcoholic steatohepatitis, and
hemochromatosis are at the highest risk, while those with cirrhosis from autoimmune
hepatitis and Wilson disease appear to have a lower risk. (See "Epidemiology and
etiologic associations of hepatocellular carcinoma", section on 'Chronic hepatitis and
cirrhosis'.)
Because of the large functional reserve of the liver, patients with HCC are frequently
asymptomatic early in its course, and the diagnosis is often delayed. Decompensation in
a patient with previously compensated cirrhosis should raise the clinical suspicion that
HCC has developed. Other common signs and symptoms of HCC are usually related to
mass effect from the tumor and include pain, early satiety, obstructive jaundice, and a
palpable mass. HCCs can rupture, causing hemoperitoneum. Paraneoplastic

manifestations include erythrocytosis, hypercalcemia, hypoglycemia, and diarrhea. (See


"Clinical features and diagnosis of primary hepatocellular carcinoma".)
The diagnosis of HCC may be suggested by marked elevations of serum alpha-fetoprotein
(AFP) or by characteristic radiographic findings. Elevated AFP is not specific for HCC since
it can also be seen in patients with acute or chronic hepatitis, gonadal tumors, and
pregnancy. However, rising serum AFP levels in a patient with cirrhosis should raise
clinical suspicion for HCC. However, a significant proportion of patients with HCC have
normal AFP levels, especially when the tumor is small. As a result, a normal AFP does not
preclude a diagnosis. (See "Clinical features and diagnosis of primary hepatocellular
carcinoma".)
Portal vein thrombosis Portal vein thrombosis can develop in patients with cirrhosis
and contribute to the development of portal hypertension. In patients with cirrhosis, the
pathogenesis is likely related to unbalanced hemostasis and slowing of portal flow.
Treatment often involves anticoagulation, though the decision to anticoagulate must take
into account the patient's risk for bleeding, particularly if esophageal varices are present.
(See "Epidemiology and pathogenesis of portal vein thrombosis in adults", section on
'Pathogenesis' and "Acute portal vein thrombosis in adults: Clinical manifestations,
diagnosis, and management" and "Chronic portal vein thrombosis in adults: Clinical
manifestations, diagnosis, and management".)
GENERAL MANAGEMENT The major goals of managing patients with cirrhosis include:
Slowing or reversing the progression of liver disease
Preventing superimposed insults to the liver
Identifying medications that require dose adjustments or should be avoided entirely
(table 2 and table 3)
Managing symptoms and laboratory abnormalities
Preventing, identifying, and treating the complications of cirrhosis
Determining the appropriateness and optimal timing for liver transplantation
Slowing or reversing the progression of liver disease Although cirrhosis is generally
considered to be irreversible in its advanced stages, the exact point at which it becomes
irreversible is unclear [14,15]. Some chronic liver diseases respond to treatment even
when the liver disease has progressed to cirrhosis. Thus, specific therapies directed
against the underlying cause of the cirrhosis should be instituted.
As examples:
Patients with hepatitis C and advanced fibrosis or cirrhosis who achieve a sustained
virologic response (SVR) with antiviral treatment have a lower risk of liver-related
mortality compared with patients who do not achieve an SVR [16]. (See "Patient
evaluation and selection for antiviral therapy for chronic hepatitis C virus infection",
section on 'Bridging fibrosis and compensated cirrhosis'.)
Abstinence from alcohol substantially improves survival in alcoholic cirrhosis. (See
"Prognosis and management of alcoholic fatty liver disease and alcoholic cirrhosis",
section on 'Abstinence'.)
Successful treatment of chronic viral hepatitis can improve long-term outcomes and
may affect fibrosis. In a study of 91 patients with chronic hepatitis C and significant

fibrosis based on liver elastography, patients who achieved a sustained virologic


response had a significant decrease in liver stiffness (and thus presumably fibrosis) 24
weeks after the end of treatment [17]. (See "Noninvasive assessment of hepatic fibrosis:
Ultrasound-based elastography".)
Preventing superimposed insults to the liver
Vaccinations Vaccination against hepatitis A and B for those who are not already
immune can help prevent superimposed insults to the liver. Other vaccinations, such a
yearly influenza vaccination, are also recommended (figure 3). (See "Immunizations for
patients with chronic liver disease".)
Avoidance of hepatotoxins Patients with cirrhosis should avoid medications,
supplements, and other substances that are commonly associated with liver injury. This
includes abused substances, such as alcohol, over-the-counter medications (such as
nonsteroidal antiinflammatory drugs), prescribed drugs with hepatotoxic side effects, and
certain herbal remedies. (See "Drug-induced liver injury" and "Hepatotoxicity due to
herbal medications and dietary supplements".)
Medication adjustments Patients with cirrhosis are at increased risk of adverse events
with many medications because of impaired hepatic metabolism or renal excretion. Many
medications require dose adjustments or should be avoided entirely (table 2 and table 3)
[18].
Issues related to the use of pain medications in patients with cirrhosis are discussed in
detail elsewhere. (See "Management of pain in patients with advanced chronic liver
disease or cirrhosis".)
Management of symptoms and laboratory abnormalities
Muscle cramps Patients with cirrhosis may experience muscle cramps, which can be
severe [19-22]. The cause is incompletely understood, although they may be related to a
reduction in effective circulating plasma volume, nerve dysfunction, and alterations in
energy metabolism [23]. If other disorders are excluded, treatments that may be helpful
include quinine sulfate, branched-chain amino acids, taurine, zinc repletion (for patients
with low levels), and correction of electrolytes. We prefer quinine sulfate if patients are
able to obtain it (200 to 300 mg at bedtime). (See "Nocturnal leg cramps", section on
'Etiology'.)
In patients suspected of having muscle cramps related to cirrhosis, other causes of pain
should be excluded. Muscle cramping related to cirrhosis is often spontaneous, chronic,
and nocturnal. If there is new onset of persistent pain, other disorders such as
rhabdomyolysis, myositis, or acute kidney injury should be considered.
Quinine sulfate has been found to be beneficial for the treatment of muscle cramps in
patients with cirrhosis, but it is no longer available through pharmacies for treatment of
cramps because of side effects including arrhythmias and thrombocytopenia [24,25].
However, it is available through some online retailers. In a meta-analysis that included
409 patients who completed participation in randomized trials, tinnitus was the only side
effect that occurred more often with quinine than with placebo. Quinine sulfate may act
by reducing the excitability of the motor nerve [23]. Note that quinine sulfate is not the
same as quinidine sulfate (the latter being an antiarrhythmic drug). (See "Nocturnal leg
cramps", section on 'Management'.)
Other treatments have shown some benefit small studies. These include branched-chain
amino acids (4 g granules three times daily) [26,27], taurine (3 g once daily) [28,29], and
vitamin E (200 mg three times daily) [30]. Branched-chain amino acids and taurine are

thought to act by correcting alterations in energy metabolism, and vitamin E is thought


to decrease circulating free radicals within cells. Correcting electrolyte abnormalities is
often recommended, though it is not known whether it improves symptoms [23].
Zinc has been used in the past and may be beneficial in patients with low zinc levels,
though its role as a therapeutic agent remains unclear [23,31]. When used, it has been
given as 220 mg twice daily. Magnesium supplementation has not specifically been
studied in patients with liver disease, but it does not appear to be beneficial in patients
with skeletal muscle cramps in general [32].
One suggested approach to treatment is [23]:
Confirm the muscle cramps are related to cirrhosis
Check electrolyte levels and replete if low
Treat with branched-chain amino acids if symptoms persist
Treat with taurine if symptoms persist
Treat with vitamin E if symptoms persist
Our approach is to treat with quinine sulfate if patients can obtain it. If not, we believe
the above approach is a reasonable alternative.
Umbilical hernias Umbilical hernias pose a management dilemma in patients with
cirrhosis, since they often develop in patients with severe liver disease and ascites who
are at high risk of complications with surgical repair [33]. Successful management using
a variety of minimally invasive surgical techniques has been reported [34-38]. However,
clinical experience has tempered our enthusiasm for elective surgical repair. We have
witnessed an unacceptably high complication and recurrence rate in our patients referred
for elective repair [39]. Liver transplantation surgeons prefer to repair hernias at the time
of transplantation and not before because many have observed high postoperative
morbidity and mortality when repair was performed before the transplantation.
We have adopted the following approach to managing umbilical hernias in patients with
cirrhosis:
Most patients with ruptured or incarcerated hernias are referred for immediate repair.
However, if incarceration is detected early, it can sometimes be reduced.
Patients with symptomatic hernias or those with marked thinning of the skin overlying
the hernia sac (a sign of impending rupture), especially if there is weeping of fluid or an
eschar on the apex of the hernia, are referred for elective repair.
Patients with asymptomatic hernias are managed conservatively, with surgical
correction of the hernia performed at the time of liver transplantation. The cornerstone of
conservative management in asymptomatic patients with umbilical hernias is aggressive
management of ascites. Elastic/Velcro abdominal binders can also help reduce pain and
minimize further enlargement of the hernia. (See "Ascites in adults with cirrhosis: Initial
therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites".)
Hyponatremia Hyponatremia is a common problem in patients with advanced cirrhosis.
The pathogenesis of hyponatremia is directly related to the hemodynamic changes and
secondary neurohumoral adaptations that occur in the setting of cirrhosis, resulting in an
impaired ability to excrete ingested water. The severity of the hyponatremia is related to

the severity of the cirrhosis. The management of hyponatremia is discussed elsewhere.


(See "Hyponatremia in patients with cirrhosis", section on 'Treatment'.)
Thrombocytopenia or elevated INR Patients with cirrhosis frequently have low platelet
counts and elevated international normalized ratios (INRs). Because the liver makes
coagulation factors as well as anticoagulant proteins, liver disease can lead to a
hypocoagulable state or a hypercoagulable state. The relative balance or imbalance of
these factors is not reflected in conventional indices of coagulation, such as the
prothrombin time, activated partial thromboplastin time, or INR. (See "Coagulation
abnormalities in patients with liver disease", section on 'Bleeding risk assessment and
prophylaxis'.)
Patients typically only need treatment for thrombocytopenia or an elevated INR if an
invasive procedure that is moderate or high risk for bleeding is planned, or in the setting
of active bleeding. It is reasonable to aim for platelet counts of at least 50,000/microL
during moderate-risk procedures [40] or interventions and platelet counts closer to
100,000/microL in high-risk situations or in the presence of active bleeding [41]. (See
"Coagulation abnormalities in patients with liver disease", section on 'Platelet
transfusion'.)
Because of inter-laboratory variation and the limited relationship of the INR to
parameters such as thrombin production, it is difficult to endorse a specific INR cutoff
requiring plasma transfusion. In addition, because of the adverse effects of plasma
infusion on portal vein pressures and collateral vessel flow, caution is warranted in the
use of plasma. A judicial approach is supported by the limited effect of the traditional
dose of two units of plasma, as this dose is unlikely to significantly alter coagulation
factor levels. (See "Coagulation abnormalities in patients with liver disease", section on
'Fresh frozen plasma' and "Clinical use of plasma components", section on 'Plasma
products'.)
An alternative to plasma infusion prior to moderate- to high-risk procedures or in the
setting of active bleeding is to measure fibrinogen levels and replace with cryoprecipitate
for fibrinogen levels less than 100 to 150 mg/dL [42]. This avoids the large volumes of
fluid associated with plasma infusion. In addition, raising fibrinogen increases the
likelihood that a "rescue" agent such as rFVIIa would be effective should there be
uncontrollable hemorrhage. (See "Coagulation abnormalities in patients with liver
disease", section on 'Cryoprecipitate' and "Coagulation abnormalities in patients with
liver disease", section on 'Recombinant factor VIIa'.)
Preventing and identifying complications Patients should be monitored for the
development of complications, and when possible, steps should be taken to prevent their
development. In particular, patients should be screened for esophageal varices and
hepatocellular carcinoma. If varices are present, prophylactic treatment with beta
blockers or esophageal variceal ligation is indicated.
Other measures to decrease the risk of complications include judicious diuresis and
avoiding proton pump inhibitors in patients without clear indications for their use
(spontaneous bacterial peritonitis); treating infections (spontaneous bacterial peritonitis,
hepatic encephalopathy); avoiding sedatives and treating hypokalemia and
hyponatremia (hepatic encephalopathy); avoiding nephrotoxic agents and aggressive
diuresis (hepatorenal syndrome); and only using urinary catheters, mechanical
ventilation, and central lines when clearly indicated (secondary infections). (See 'Major
complications' above.)
Variceal bleeding: All patients with cirrhosis should undergo screening for esophageal
varices with upper endoscopy so that prophylactic therapy can be given to those with
varices that are at increased risk for bleeding and to determine the risk of variceal
hemorrhage. Prophylactic therapy most commonly involves treatment with a

nonselective beta blocker or endoscopic variceal ligation, which reduces the risk of
variceal bleeding. (See "Primary and pre-primary prophylaxis against variceal
hemorrhage in patients with cirrhosis".)
Hepatocellular carcinoma: Patients with cirrhosis should undergo surveillance with
ultrasonography every six months. (See "Prevention of hepatocellular carcinoma and
recommendations for surveillance in adults with chronic liver disease", section on
'Surveillance methods'.)
Spontaneous bacterial peritonitis: The risk of spontaneous bacterial peritonitis
(SBP) can be reduced by efforts to judiciously diurese patients since diuresis
concentrates ascitic fluid, thereby raising ascitic fluid opsonic activity. Early recognition
and aggressive treatment of localized infections (eg, cystitis, cellulitis) can also help to
prevent bacteremia and SBP. Proton pump inhibitor use has been associated with an
increased risk of SBP, so proton pump inhibitors should only be given to patients who
have clear indications for their use. Finally, prophylactic antibiotics aimed at
decontaminating the gut have a role in specific clinical settings. (See "Spontaneous
bacterial peritonitis in adults: Treatment and prophylaxis".)
Hepatic encephalopathy: Patients with cirrhosis should be evaluated regularly for
hepatic encephalopathy, the earliest features of which can be subtle. Events that can
precipitate hepatic encephalopathy include the development of variceal bleeding,
infection (such as SBP), the administration of sedatives, hypokalemia, and hyponatremia,
all of which should be corrected/avoided whenever possible (table 4). (See "Hepatic
encephalopathy in adults: Clinical manifestations and diagnosis" and "Hepatic
encephalopathy in adults: Treatment".)
Portal vein thrombosis: Enoxaparin may be effective for preventing portal vein
thrombosis (PVT) in patients with cirrhosis, though it is not used routinely. If it is to be
used, we suggest eradication of varices (if present) prior to initiation of anticoagulation
when possible. (See "Chronic portal vein thrombosis in adults: Clinical manifestations,
diagnosis, and management", section on 'Prevention in patients with cirrhosis' and
"Primary and pre-primary prophylaxis against variceal hemorrhage in patients with
cirrhosis", section on 'Endoscopic variceal ligation'.)
Hepatorenal syndrome: Nephrotoxic agents (such as aminoglycosides) and vigorous
diuresis should be avoided in patients with cirrhosis since they can precipitate renal
failure. (See "Hepatorenal syndrome".)
Secondary infections: Patients with cirrhosis who are hospitalized often acquire
infections while in the hospital. Factors that have been associated with hospital-acquired
secondary infections in patients with cirrhosis include the use of urinary catheters,
mechanical ventilation, and the placement of central lines [43]. Many of these
interventions are performed routinely (such as placement of urinary catheters to
measure urine output). However, avoiding these interventions unless they are absolutely
necessary may decrease the risk of acquiring an infection while in the hospital, and it is
our practice to only use these interventions when clearly indicated.
In a study of 207 patients with cirrhosis who were admitted with or developed an
infection during hospitalization, 50 (24 percent) developed a second infection during
hospitalization [43]. Respiratory infections were the most common (14 patients), followed
by urinary tract infections (13 patients), and Clostridium difficile. Of the urinary tract
infections, 6 (46 percent) were related to the use of bladder catheters. Other factors
associated with second infections included intensive care unit admission, the use of
central lines, mechanical ventilation, shock, renal replacement therapy, and hepatic
encephalopathy. Overall mortality was 39 percent, but it was 48 percent for those who
developed a second infection during admission.

Treatment of complications The treatment of the complications of cirrhosis is discussed


in the respective topic reviews. (See 'Major complications' above.)
Liver transplantation Liver transplantation is the definitive treatment for patients with
decompensated cirrhosis. It is important to determine whether patients may be eligible
for transplantation and to refer them to a transplant center for evaluation. Several
guidelines are available which help determine when referral for liver transplantation may
be beneficial. The decision to proceed to liver transplantation (either cadaveric or live
donor) depends upon the severity of disease, quality of life, and the absence of
contraindications. (See "Liver transplantation in adults: Patient selection and
pretransplantation evaluation".)
PROGNOSIS The prognosis of cirrhosis is highly variable since it is influenced by a
number of factors, including etiology, severity, presence of complications, and comorbid
diseases. Once decompensation occurs (eg, the patient develops variceal bleeding,
hepatic encephalopathy, or spontaneous bacterial peritonitis), mortality rates are high.
(See 'Decompensated cirrhosis' below.)
Compensated cirrhosis Patients with cirrhosis who have not developed major
complications are classified as having compensated cirrhosis. The median survival of
patients with compensated cirrhosis is >12 years [44]. Patients with varices but who
have not developed variceal bleeding are considered to have compensated cirrhosis,
though their prognosis is worse than that of patients who have compensated cirrhosis
without varices (3.4 versus 1.0 percent one-year mortality rates) [44].
Decompensated cirrhosis Patients who have developed complications of cirrhosis, such
as variceal hemorrhage, ascites, spontaneous bacterial peritonitis, hepatocellular
carcinoma, hepatorenal syndrome, or hepatopulmonary syndrome are considered to
have decompensated cirrhosis and have a worse prognosis than those with compensated
cirrhosis. (See 'Major complications' above.)
A systematic review found that the median survival was 6 months in patients with
decompensated cirrhosis and a Child-Pugh score 12 or a MELD score 21 [45]. In
addition, patients with decompensated cirrhosis who had been hospitalized with an acute
liver-related illness (eg, variceal hemorrhage or spontaneous bacterial peritonitis) had a
median survival of 6 months if the Child-Pugh score was 12 or the MELD score was
18.
An important factor related to survival is mean arterial pressure. In a series of 139
patients with cirrhosis and ascites, a mean arterial pressure of 82 mmHg was an
important predictor of survival [46]. Among patients with a mean arterial pressure 82
mmHg, survival was 20 percent at 24 months and 0 percent at 48 months (compared
with 70 and 50 percent, respectively, for patients with a mean arterial pressure >82
mmHg).
Another factor that may be associated with survival is the presence of relative adrenal
insufficiency [47,48]. In a study of 143 patients who were admitted to the hospital with
decompensated cirrhosis, relative adrenal insufficiency was detected in 37 patients (26
percent) [47]. At the time of presentation, compared with patients who did not have
relative adrenal insufficiency, patients with relative adrenal insufficiency had lower mean
arterial pressures (76 versus 83 mmHg) and serum sodium levels (131 versus 135
mEq/L) and had higher blood urea nitrogen levels (32 versus 24 mg/dL). During three
months of follow-up, patients with relative adrenal insufficiency were more likely to
develop infection (41 versus 21 percent), severe sepsis (27 versus 9 percent), type-1
hepatorenal syndrome (16 versus 3 percent), and death (22 versus 7 percent). (See
"Diagnosis of adrenal insufficiency in adults".)

Among patients with cirrhosis and severe septic shock, administration of hydrocortisone
may improve outcomes [49]. (See "Treatment of adrenal insufficiency in adults", section
on 'Glucocorticoid regimens'.)
Other factors associated with poor survival in patients with decompensated cirrhosis
included hepatopulmonary syndrome, rapidly progressive hepatorenal syndrome, and
intensive care unit admission for complications of liver disease along with hypotension
requiring pressor support, serum creatinine >1.5 mg/dL, or jaundice.
Patients with decompensated cirrhosis often require liver transplantation. For those who
are not candidates, hospice care can be considered for patients with predicted survival of
6 months. (See "Liver transplantation in adults: Patient selection and pretransplantation
evaluation" and "Palliative care: Benefits, services, and models of care".)
Predictive models Multiple studies have attempted to predict the prognosis of patients
with cirrhosis based on clinical and laboratory information. Two commonly used models
are the Child-Pugh classification and the Model for End Stage Liver Disease (MELD).
Child-Pugh classification The Child-Pugh classification (table 5) has been used to
assess the risk of non-shunt operations in patients with cirrhosis (calculator 1 and
calculator 2) [50]. It is a modification of the Child-Turcotte classification which
incorporated five variables that were designed to stratify the risk of portacaval shunt
surgery in patients with cirrhosis. The variables included the serum albumin and bilirubin,
ascites, encephalopathy, and nutritional status (table 6) [51]. The Child-Pugh
classification replaces nutritional status with prothrombin time. The score ranges from 5
to 15. Patients with a score of 5 or 6 have Child-Pugh class A cirrhosis (well-compensated
cirrhosis), those with a score of 7 to 9 have Child-Pugh class B cirrhosis (significant
functional compromise), and those with a score of 10 to 15 have Child-Pugh class C
cirrhosis (decompensated cirrhosis).
In a review of 92 patients with cirrhosis who underwent abdominal surgery, the mortality
rate was 10 percent for patients with Child-Pugh class A cirrhosis, 30 percent for patients
with Child-Pugh class B cirrhosis, and 82 percent for patients with Child-Pugh class C
cirrhosis [52]. Other studies have validated the utility of the Child-Pugh classification for
the assessment of surgical risk [53]. (See "Assessing surgical risk in patients with liver
disease".)
The Child-Pugh classification system also correlates with survival in patients not
undergoing surgery; one-year survival rates for patients with Child-Pugh class A, B, and C
cirrhosis are approximately 100, 80, and 45 percent, respectively [54,55]. Child-Pugh
class is also associated with the likelihood of developing of complications of cirrhosis. As
an example, patients with Child-Pugh class C cirrhosis are much more likely to develop
variceal hemorrhage than those with Child-Pugh class A cirrhosis [56].
MELD score Another model to predict prognosis in patients with cirrhosis is the Model
for End Stage Liver Disease (MELD) score. It is based upon bilirubin levels, creatinine,
INR, and the etiology of cirrhosis (calculator 3 and calculator 4). The MELD score has
been adopted for use in prioritizing patients awaiting liver transplantation and has an
expanding role in predicting outcomes in patients with liver disease in the nontransplantation setting. (See "Model for End-stage Liver Disease (MELD)".)
WHEN TO REFER TO A SPECIALIST Referral to a hepatologist is recommended if the
patient develops decompensated cirrhosis or major complications of cirrhosis. Patients
with a MELD score 10 should be referred to a liver transplantation center for evaluation.
In addition, referral to a hepatologist should be considered if the patient requires
treatment for the underlying cause of the cirrhosis (eg, hepatitis C, autoimmune
hepatitis) or if the clinician managing the patient would like the assistance of a

hepatologist in the patient's general management. (See "Liver transplantation in adults:


Patient selection and pretransplantation evaluation", section on 'Cirrhosis'.)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials,
"The Basics" and "Beyond the Basics." The Basics patient education pieces are written in
plain language, at the 5th to 6th grade reading level, and they answer the four or five key
questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10 th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on "patient info" and the keyword(s) of
interest.)
Basics topics (see "Patient information: Cirrhosis (The Basics)" and "Patient information:
Liver cancer (The Basics)")
Beyond the Basics topics (see "Patient information: Cirrhosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Cirrhosis represents a late stage of progressive hepatic fibrosis characterized by
distortion of the hepatic architecture and the formation of regenerative nodules. It is
generally considered to be irreversible in its advanced stages. In earlier stages, specific
treatments aimed at the underlying cause of liver disease may improve or even reverse
cirrhosis. (See 'Introduction' above.)
Patients with cirrhosis are susceptible to a variety of complications, and their life
expectancy can be markedly reduced. Major complications of cirrhosis include (see 'Major
complications' above):
Variceal hemorrhage
Ascites
Spontaneous bacterial peritonitis
Hepatic encephalopathy
Hepatocellular carcinoma
Hepatorenal syndrome
Hepatopulmonary syndrome
Portal vein thrombosis
Cardiomyopathy
The major goals of managing patients with cirrhosis include (see 'General management'
above):

Slowing or reversing the progression of liver disease (see 'Slowing or reversing the
progression of liver disease' above)
Preventing superimposed insults to the liver (see 'Preventing superimposed insults to
the liver' above)
Identifying medications that require dose adjustments or should be avoided entirely
(table 2 and table 3) (see 'Medication adjustments' above)
Managing symptoms and laboratory abnormalities (see 'Management of symptoms and
laboratory abnormalities' above)
Preventing and treating the complications of cirrhosis (see 'Preventing and identifying
complications' above)
Determining the appropriateness and optimal timing for liver transplantation (see 'Liver
transplantation' above)
The prognosis of cirrhosis is highly variable since it is influenced by a number of factors,
including etiology, severity, presence of complications, and comorbid diseases. Once
decompensation occurs (eg, the patient develops variceal bleeding, hepatic
encephalopathy, or spontaneous bacterial peritonitis), mortality rates are high. (See
'Decompensated cirrhosis' above.)