CIRRHOSIS

PRESENTOR: DR ANIL KUMAR SAH

MODERATOR: DR SUBASH BHATTARAI
CONTENTS: CIRRHOSIS
• DEFINITION
• CAUSES
• PATHOGENESIS
• C/F
• COMPLICATIONS
• DIAGNOSIS
• PROGNOSIS
• MANAGEMENT
DEFINITION
• Cirrhosis is a final pathway for a wide variety of chronic liver diseases
• Histo-pathologically defined as the end stage liver disease disruption of
the liver architecture by fibrotic bands that divide the liver into nodules
of regenerating liver parenchyma

• At present, cirrhosis (fibrosis) is reversible if the cause is removed (most

apparent in tx of chronic hepatitis C)
CAUSES OF CIRRHOSIS
A. Alcohol (ALD is the MCC of liver cirrhosis)

B. CHRONIC VIRAL HEPATITIS:

1. Hepatitis B ± D
2. Hepatitis C

C. METABOLIC
1. NAFLD
2. α1 Antitrypsin deficiency, Galactosemia, Glycogen storage disease,
Hemochromatosis, Wilson disease
C. AUTOIMMUNE
1. Autoimmune hepatitis
2. PBC
3. PSC

D. BILIARY
1. Atresia, Stone, Tumor
E. VASCULAR
1. Budd-Chiari syndrome

F. GENETIC
1. CF, Lysosomal acid lipase deficiency

G. IATROGENIC
1. Biliary injury Drugs: high-dose vitamin A, methotrexate
H. CARDIAC CIRRHOSIS
Based on this etiology, patients can be divided into broad groups:
• alcohol-associated cirrhosis,
• cirrhosis due to chronic viral hepatitis,
• nonalcoholic fatty liver disease,
• biliary cirrhosis,
• and other, less common causes, such as cardiac cirrhosis, cryptogenic
cirrhosis, and other miscellaneous causes.
PATHOGENESIS

• Architecture distortion with the formation of regenerative nodules. 

decrease in hepatocellular mass, and thus function, and an alteration
of blood flow.
 Portal Hypertension & Ascites
• Alcohol, Chronic viral hepatitis, NAFLD

• Chronic inflammation  Hepatocytes damage  Activation of kupffer

cells  Releases cytokines & ROS activates stellate cells  release
cytokines (IL, TNF alfa, TGF)  Stellate cells transfer into myofibroblast
like cells (capable of producing collagen, cytokines)  Normal matrix is
space of disse is replaced by collagen (mostly 1 & 3) & fibronectin 
• Fibrosis & regenerative nodules (d/t compensatory proliferation) causing
distortion of architecture of liver parenchyma (Cirrhosis)
• Increased intrahepatic resistance
• evidence suggest that, despite the overproduction of
vasodilator factors such as NO in the splanchnic and
systemic circulation, in cirrhosis, the production of NO
from endothelial nitric oxide synthase is reduced in the
intrahepatic circulation of cirrhotic livers and contributes
to increased intrahepatic resistance.
• Also myofibroblast increase the vascular tone  inc
resistance.
• Kupffer cells induce production of cytokines & ROS 
increase intrahepatic vascular tone
• Increased intrahepatic resistance & marked disturbance in
the intrahepatic circulation  increased resistance to portal
venous flow  Portal HTN
• Portal HTN (hepatic venous pressure gradient (HVPG), defined as
the difference between wedged and free hepatic venous pressure,
measured by hepatic vein catheterization. clinically significant
portal hypertension is defined as an HVPG above 10 to 12 mm Hg,
because this is the threshold for clinical manifestations of portal
hypertension (e.g., ascites) HVPG above 16 mm Hg identifies
patients at high risk for mortality, and an HVPG above 20 mm Hg is
associated with treatment failure and mortality in patients with
cirrhosis and acute variceal bleeding)
• Portal HTN  increase in release of several vasodilating factors, such
as NO, carbon monoxide (produced by heme oxygenase during heme
metabolism to biliverdin), Circulating vasodilators (glucagon: studies
suggest there is increase in glucagon in cirrhosis & portal HTN) 

• splanchnic arterial vasodilation

 CLINICAL FEATURES
Asymptomatic:
Non specific sx:
• Anorexia, nausea, vomiting, fatigure, wt loss, RUQ pain
Features of portal HTN
• Ascites (abd distension)
• Congestive splenomegaly (clinical bed side finding)
• Porto-systemic shunt
• Lower gastro-esophageal: Esophageal varices (bleed hematemesis)
• Umbilicus: caput medusa: . Are dilated abd vein with flow away from the umbilicus,
toward the inferior vena cava in the infraumbilical area and toward the superior
vena cava in the supraumbilical area, suggest intrahepatic portal hypertension .
• Rectum: Hemorrhoids

Features of impaired hepatic function

Features of impaired hepatic function
• Reduced protein synthesis:
• Hypoalbuminemia: Ascites, leukonychia,
• Reduced clotting factor: bleeding manifestation- petechia
• Reduced detoxification: Hepatic encephalopathy
• Reduced hepatic clearance of precursor androstenedione: peripheral
conversion to estrogen (hyperestrogenaemia)
• Spider naevi (central pulsating arteriole with radiating small vessels): more than 2
to 3 spider telangiectasias are considered abnormal. Site: hands, face and upper
chest
• Palmar erythema: Red thenar and hypothenar (d/t local vasodilation)
• Gynecomastia, breast atrophy in female, b/l testicular atrophy & infertility, loss of
libido,
• Loss of axillary/pubic hair, menstrual irregularities
• Failure to excrete bilirubin: Jaundice
OTHERS:
• Fat soluble vit def (vit A-night blindness; Vit D- osteoporosis, Vit k-
bleeding )
• Loss of S.C fat  paper thin skin with marked fold called Paper monkey skin
• Terry’s nails are characterized by proximal nail bed pallor which can also
involve the entire nail plate, with predominant involvement of the thumb
and index finger
• Parotid enlargement is also a feature of cirrhosis, especially alcohol-
associated cirrhosis
• Pigmentation is most striking in haemochromatosis and in any cirrhosis
associated with prolonged cholestasis.
• Clubbing of the fingers and toes is not a sign of cirrhosis but is seen in
combination with hypoxia in hepatopulmonary syndrome.
• Anemia: d/t chronic infla,, B.M suppression, chronic blood loss.
CLINICAL FEATURES
• clinicians need to differentiate between those who have stable,
compensated cirrhosis and those who have decompensated cirrhosis.
• Patients who have developed ascites, hepatic encephalopathy, or
variceal bleeding are classified as decompensated. They should be
considered for liver transplantation, particularly if the
decompensations are poorly controlled.
COMPLICATIONS
1. PORTAL HTN: ascites, variceal bleed
2. GIT DISORDER: non variceal bleed, protein losing enteropathy
3. BACTERIAL INFECTION: SBP, UTI, pneumonia, cellulitis
4. RENAL DISORDER: HRS,
5. CARDIOPULMONARY DISORDER: Hepatic hydrothorax,
cardiomyopathy, hepatopulmonary synd
6. NEUROPSYCHIATRIC DISORDER: HE, depression
7. HEMATOLOGICAL DISORDER: Anemia, impaired coagulation,
8. METABOLIC DISORDER: Hypogonadism, Malnutrition, Osteoporosis
9. MALIGNANCY: Cholangiocarcinoma, HCC
10. Others: erectile dysfunction, fatigue, muscle cramps
DIAGNOSIS
• Although cirrhosis is strictly a histologic diagnosis a combination of
clinical, laboratory, and imaging features can help confirm a diagnosis
of cirrhosis.
• Biopsy: gold
standard for dx of
cirrhosis

Normal portal tract

Stage 0: mild steatosis, no fibrosis
Stage1: significant increase in collagen (fibrosis) in the portal
tract, but does not involve the surrounding periportal acinar
parenchyma
Stage 2: periportal fibrosis + expansion of fibrosis to
surrounding periportal acinar parenchyma (black arrow)
Stage 3: bridging fibrosis
Stage 4 (Cirrhosis): normal liver architecture is completely
distorted and replaced by regenerative nodules that are
separated by fibrous septa
• Patients with a history of chronic liver disease with gastroesophageal
varices, ascites, or hepatic encephalopathy are likely to have cirrhosis,
and liver biopsy is not essential in such cases for confirming cirrhosis
• In patients with a diagnosis of CLD without these complications, physical
findings of an enlarged left hepatic lobe with splenomegaly, along with
the cutaneous stigmata of liver disease cirrhosis, especially in the setting
of thrombocytopenia and impaired hepatic synthetic function (e.g.,
hypoalbuminemia, prolongation of the prothrombin time).
• If physical and laboratory findings are not suggestive of cirrhosis,
imaging studies can help make a diagnosis of cirrhosis. A small nodular
liver with splenomegaly and intra-abdominal collaterals and the
presence of ascites on abdominal US (or other cross-sectional imaging
study) suggests cirrhosis
• Where available fibroelastography or magnetic resonance elastography
(MRE) can help confirm a diagnosis of cirrhosis
• In fibroelastography (vibration-controlled transient elastography) a liver
stiffness greater than 14 kPa (kilopascals) suggests cirrhosis, with > 21
kPa associated with portal hypertension and its complications.
esophageal varices are unlikely if the hepatic stiffness is less than 19.5
kPa
• On MRE, liver stiffness values greater than 5.9 kPa suggest cirrhosis, and
a liver biopsy is typically not required to confirm the diagnosis
• . Increasing spleen stiffness on US elastography or MRE is associated
with the onset of portal hypertension
• Note: t liver stiffness is overestimated in the postprandial state and in
the presence of hepatic inflammation, cholestasis, and right-sided heart
failure.
• A serum AST/platelet ratio index (APRI) of greater than 2 suggests
cirrhosis,
• APRI = (AST/upper limit of normal AST) × (100/platelet count [×103/mm3])
• Ascites and a platelet count of less than 160,000/mm3 render the
diagnosis of cirrhosis more likely
Natural history of chronic liver disease
• Chronic liver disease 
• Compensated cirrhosis: these complications are absent. Stage 1 &2
• Decompensated cirrhosis: The development of complications of variceal
hemorrhage, ascites, encephalopathy, jaundice. Stage3 & 4
• Acute on chronic liver failure

Stages of cirrhosis
• Stage 1: no ascites; no varices
• Stage 2: no ascites; varices without bleeding
• Stage 3: ascites; with/without varices bleed
• Stage 4: variceal bleed; with/without ascites
MANAGEMENT
• surveillance for HCC with US of the liver every 6 months
• cessation of alcohol use
• Weight loss  a/w reduction in portal pressure and reduced risk of hepatic
decompensation; however, abdominal exercises that increase intra-abdominal
pressure and the risk for variceal hemorrhage should be avoided
• Immunization  against HAV, HBV, pneumococcal pneumonia, and influenza is
recommended. Live-attenuated vaccines are not C/I in patients with cirrhosis
• Diet Patients with cirrhosis have protein-calorie malnutrition, and frequent
high-calorie small meals, as well as bedtime snacks, are recommended. Fat-
soluble vitamins and zinc levels should be monitored, with replacement if
required. daily protein intake of 1.2–1.5 g/kg. late evening snack will help to
minimise overnight fasting which could otherwise trigger a catabolic state in
cirrhosis.
• Acetaminophen in doses of up to 2 g daily may be used. Aspirin and
other NSAIDs should be avoided in patients with decompensated
cirrhosis, including those with ascites.
• Aminoglycosides are contraindicated, but other antibiotics are
acceptable, as are statins for treatment of hyperlipidemia.

• In patients with DM,

• Compensated cirrhosis oral hypoglycemic agents may be used
• decompensated cirrhosis  insulin is preferred.
• Patients with chronic viral hepatitis who use statins have a reduced risk
of hepatic decompensation and mortality. The use of low molecular
weight heparin may delay decompensation even in patients without
portal vein thrombosis but is currently not recommended

• no clear management for fatigue, muscle cramps & sexual dysfunction.

• Fatigue: always r/o encephalopathy, anemia & thyroid disorder
• Muscle cramp: d/t disease severity or diuretics
• Erectile dysfunction: PDE inhibitors are ineffective

• Depression in cirrhosis: SSRI & mirtazapine are safe and effective

 PROGNOSIS
• In compensated stages, the MCC of death is cardiovascular disease,
followed by stroke, malignancy, and renal disease
• In decompensated stage, the death occur d/t hepatic and extrahepatic
organ failure
• The median survival in patients with compensated cirrhosis is 9 to 12
years, compared with 2 years in those with decompensated cirrhosis.
• As compared with the general population, persons with compensated
cirrhosis have a 5-fold increased risk of death, whereas patients with
decompensated cirrhosis have a 10-fold increased risk.
• Patients with an infection have a 4-fold increase in mortality compared
with cirrhotic patients without an infection. Patients with renal failure
have a 7- to 8-fold increased risk of death compared with patients
without renal failure
• Child–Pugh and MELD (Model for End-stage Liver Disease) scores can be
used to assess prognosis in chronic liver disease
 ACUTE-ON-CHRONIC LIVER FAILURE
(ACLF)
Definition: “a condition in patients with underlying CLD with or without
cirrhosis that is a/w mortality within 3 months in the absence of
treatment of the underlying liver disease, liver support, or liver
transplantation.”
ACLF may be further divided into 3 types depending on the underlying
liver disease,
• type A, underlying chronic liver disease without cirrhosis;
• type B, underlying compensated cirrhosis; and
• type C, underlying decompensated cirrhosis
PATHOGENESIS
precipitating events leading to hepatic and extrahepatic organ failure
are (HBV reactivation, HEV superinfection in patients with CLD, and
alcohol-associated hepatitis, bacterial infection).
HOW?
- sterile inflammation secondary to precipitating factors such as
excessive alcohol-induced hepatocyte death and inflammation
secondary to bacterial infections.
• However, routine use of antibiotics in patients with cirrhosis with the goal of
preventing complications of cirrhosis is not currently recommended
- ACLF pt have significant suppression of the innate immune system
C/F
Features of systemic inflammatory response syndrome, with fever,
tachycardia, tachypnea, and leukocytosis. They also have manifestations of
organ failure like
TREATMENT
-Treating ppt factors
• Alcohol-associated hepatitis - Glucocorticoids
• Extrahepatic organ failure - Organ support
• hepatorenal syndrome- terlipressin (however, ACLF pt have poor response to it)
• Hepatitis B - Antiviral agent
• Infections – Antibiotics

-LIVER TRANPLANT (LT)

• offers the only hope of long-term survival to patients with ACLF
• Patients with multiple organ failures, however, may be too sick for LT