LORD MAHAVIRA HOMOEOPATHIC MEDICAL COLLEGE & HOSPITAL

(Dr. Hahnemann Chowk) LUDHIANA

DEPARTMENT PRACTICE OF
OF MEDICINE

PRESENTATION ON CIRRHOSIS OF
LIVER
UNDER THE GUIDANCE OF : BY :
PROF. (DR.) PARMOD KUMAR SIMRANJEET SINGH
M.D. (Hom.) SIMRAN KAUR
HoD (PRACTICE OF SIMRAN BANSAL
MEDICINE)
CIRRHOSIS
OF THE
LIVER
 DEFINITION
• Cirrhosis is a common chronic, progressive and
diffusive liver disease, caused by one or several
agents act repeatedly and persistently.

• Histologically, cirrhosis is an irreversible

alteration of the liver architecture, consisting of
hepatic fibrosis and areas of nodular regeneration
 EPIDEMIOLOGY
• Worldwide major heath problem
• Over 500,000 deaths per year
• Over 20% were latent
• 2 ~ 10% in postmortem examination
• Common and death leading disease in China
EtiolOGY & PATHOGENESIS

• Viral hepatitis • Hepatic-Venous

• Parasites outflow obstruction
(schistosomiasis) • Toxicant and drugs
• Alcoholic liver • Metabolic abnormality
disease • Malnutrition
• Cholestasis • Cryptogenic cirrhosis
 Viral hepatitis

• HAV
HBV

• HEV
HCV

• HBV + HDV
 Viral hepatitis (HBV)
• Global prevalence: >300 million carriers
5% world population
• Varies widely
High prevalence: 8% ~ 15%
Far East (southeast Asia China Philippines Indonesia)
Middle East Africa parts of South America
Intermediate prevalence: 2% ~ 7%
Japan parts of south America parts of central Asia
eastern and southern Europe
Low prevalence: <2%
US Canada northern Europe Australia
 Viral hepatitis
• Elimination of viral infected hepatocytes is dependent on
recognition of viral determinants in association with HLA
proteins on the infected hepatocytes by cytotoxic T cells.

• HLA protein display is modulated by exposure to

interferon and cytotoxic T cell, NK lytic processes.

• During chronic HBV infection, infected liver cells failed

to induce IFN. Therefore, viral protein synthesis is not
decreased, HLA protein display is not enhanced.
 Parasites (Schistosomiasis)

• Ova deposited in the portal zones

• Exciting a fibrous tissue reaction
• Co-existence of malaria and cirrhosis reflects

malnutrition, viral hepatitis and toxic factors

Alcoholic liver disease
• 1/3 cause of cirrhosis in Western country
• Most important factor:
“threshold” dose: 600 Kg (men) 150~300 Kg (women)
average daily consumption of alcohol
> 40 ~ 80 g/D, over 10 ~ 15 years

• Liver: primary site of ethanol metabolism

• Ethanol can be oxidized by three enzymes systems
ADH CYP2E1 catalase
 Alcoholic liver disease
Mechanism
• Direct effect by ethanol, or its first metabolite
(acetaldehyde redox shift oxidant stress)

• Cell-mediated immune

Three histopathologic lesion:

fatty liver, alcoholic hepatitis, cirrhosis
 Biliary cirrhosis
Primary Biliary Cirrhosis:
• Progressive destruction of small and intrahepatic
bile ducts
• Prevalence: 40~150 cases/million
• Women >90 of cases 50y
• Abnormal immunoregulation
• Associated with HLA phenotyeps
 Biliary cirrhosis

Secondary biliary cirrhosis:

Obstruction of the biliary tree, further divided

into
two groups
intra-hepatic and extra-hepatic obstruction
Hepatic-Venous outflow obstruction

• Veno-occlusive disease

• Budd-chiari syndrome

• Constrictive pericarditis

• Chronic congestive heart failure

 Toxicant and drugs

• Tetrachloride carbon
• - methyldopa
• Tetracycline
• Phosphorus
• Arsenic
 Metabolic abnormality

• Iron storage disease (Hemochromatosis)

• Copper storage disease (Wilson’s disease)

 Malnutrition

• Chronic inflammatory bowel disease

• Prolonged lack of dietary proteins and vitamins

 Cryptogenic cirrhosis

• Etiology is unknown

• Viral infection are suscepted in some cases

 Pathophysiology
• Alcoholic cirrhosis – accumulation of fat
and scar formation in the liver cells
• Postnecrotic cirrhosis – broad bands of scar
tissue resulted from viral, toxic, or
autoimmune hepatitis
• Biliary cirrhosis – diffuse fibrosis with
jaundice from chronic biliary obstruction
• Cardiac cirrhosis – from long-standing right
sided heart failure
Pathology and classification

Histopathological diagnosis:

• Excessive fibrous tissue

• Regenerating nodules

• Complete distortion of the normal relationship

of hepatic venous outflow radicles and portal veins.
 Anatomical types of
regenerating nodules

• Micronodular

• Macronodular

• Mixed cirrhosis
 Micronodular cirrhosis
• Features: Thick regular septa
Regenerating small nodules
(<3mm)
Involvement of every lobule
• Alcoholism
• Malnutrition
• Biliary obstruction
• Hemochromatosis
 Macronodular cirrhosis

• Features: Septa
Nodules of variable size
(>3mm, even 1~ 3 cm)
Normal lobules in the large
nodules

• Two subtypes: postnecrotic

posthepatitic
 Macronodular cirrhosis

Postnecrotic type:
• Coarsely scarred liver
• Large nodules surrounded by broad fibrous septa
• Clumping togathered numerous portal trials

• Toxic cirrhosis
• Cryptogenic cirrhosis
• Multilobular cirrhosis
 Macronodular cirrhosis

Posthepatitic type:
• Macronodules separated by slender fibrous strands
• Connect individual portal areas to each other

• Viral hepatitis
• Wilson’s disease
 Mixed cirrhosis
Features:

• Presenting both micro- and macronodules

• From micronodules to macronodules

• Alcoholism
• Antitrypsin deficiency
 Some aspects of pathology

• The most useful morphologic classification:

gross appearance of the liver
• The morphologic diagnosis of cirrhosis is more
reliable than the histopathological diagnosis
• Schistosomiasis: incomplete septal cirrhosis
coarse portal fibrosis
• Initially enlarged/subsequcetly shrinks
 Clinical manifestation

• Onset: Cryptical and slowly progressive

Majority: 3~5 years or 10 years
Minority: 3~6 months

• Stages: Compensated
Decompensated
 Compensated stage
• Fatigue
• Loss of appetite
• Anorexia
• Abdominal discomfort
• Abdominal pain

• Hepatomegaly (slightly or moderately)

• Splenomegaly
 Decompensated stage

• Deterioration of liver function

• Feature of portal hypertention

 Deterioration of liver function
• General deterioration
Deterioration of heath, anorexia, weight loss, weakness, fatigue,
Flatulent dyspepsia, abdominal distress, swelling of legs or abdomen,
mild fever, loss of libido and hemorrhage.

• Findings of physical examination

Jaundice
Dermatological and sexual signs
Liver (enlarge or shrunken)
 Jaundice

It always implies liver cell destruction

exceeds the capacity for regeneration
 Dermatologic and sexual signs

• Skin pigmentation
• Clubbing fingers
• Spider angioma
• Liver palms (palmar erythema)
• Purpura
• Spontaneous bruising / epistaxes
 Dermatologic and sexual signs
• Feminization and hypogonadism
Gynecomastia
testicular atrophy
sparse body hair
changes in hair distribution
menstrual irregularities

Mechanism: serum testosterone  estrogens 

 Liver
• Early stage
Enlarged and palpable
firm regular edge
a fine to coarsely nodular surface
• Later stage
Shrunk and impalpable
Features of portal hypertension

• Portal-systemic collaterals

• Ascites

• Splenomegaly
Anatomy and physiology of portal venous
system

• Begins in the capillaries of the intestines

• Terminates in the hepatic sinusoids
• Formed by the confluence of the superior and inferior
mesenteric veins and splenic vein
• Liver receives 1500ml/min, 2/3 from portal vein
Hepatic artery provides 50% oxygen
• The pressure within the sinusoids is low
• Lack of valves
: Between the splanchnic venules and the heart
 Portal-systemic collaterals

• Esophageal and gastric varices

• Dilation of the remnant of the umbilical vein

• Dilation of abdominal veins

• Hemorrhoidial venous collaterals

 Splenomegaly
• Slightly or moderatory enlarged
• Hypersplenism
Leukopenia
Thrombocytopenia
Anemia
 Ascites
• Prominent feature of portal-hypertension

• 70% of patients are positive

• An early sign in presinusoidal portal hypertension

relative late in intrahepatic portal hypertension

• Massive ascites: abdominal herniae ( 腹疝）

 Complications

• Upper gastrointestinal bleeding

• Hepatic encephalopathy
• Infection
• Hepatorenal syndrome
• Primary liver cancer
• Imbalance of electrolytes and acid-alkaline
 Upper gastrointestinal bleeding

• Major complication
• Incredible high mortality
• Source of bleeding:
esophageal varices 60%~80%
gastric varices 7%
congestive gastropathy 5%~20%
(paptic ulcer, acute erosive gastritis etc)
 Hepatic encephalopathy

The most severe and deadly complications

 Infection
Increased risk for bacterial infection

pneumonia
biliary infection
E.coli infection and
spontaneous bacterial peritonitis (SBP)
 SBP
• Pathogen of SBP: gram’s negative bacteria

•Features of SBP: fever, abdominal pain or tenderness

decreased bowel sounds
•Suspected patients: sudden onset of HE or hypotension

•Diagnosis: elevated ascites fluid white blood cells

positive ascitic fluid culture
 Hepatorenal syndrome
• Decreased renal function due to severe liver disease
• Histologically normal kidney
• Involved factors
Sympathetic nervous system
Renin-angiotensin-aldosterone
Prostaglandins
Endotoxemia
Others ( vasopressin , leukotriene etc)
 Primary liver cancer
• Suspected signs
Hepatomegaly within short time
Persistent abdominal pain
Enlarged liver with uneven surface or mass
Bloody ascites

• Serum α-fetoprotein (α-FP) 70%

Imbalance of electrolytes and acid-alkaline

• Hyponatraemia

• Hypokalaemia

• Metabolic alkalosis
 Laboratory and other tests

• Urine
• Serum
• Hematology
• Ultrasonograply
• Barium esophagogram
• Endoscopy
• Liver biopsy
 Diagnosis
• Patients with a history of viral hepatitis, prolonged
alcohol overconsumption, schistosome infection,
hemochromatosis
• Features of deterioration of liver function and
portal hypertension
• Enlarged or shrunk liver with nodular surface
• Abnormal liver function tests
• Liver biopsy shows widespread fibrosis with
nodular regeneration
Complete diagnosis

Etiology

Morphology

Hepatic function
Specific clinical clues to
etiology of cirrhosis
 Posthepatitic cirrhosis
• Previous acute hepatitis, transfusion, illicit drugs

• Multiorgan involment such as rash, arthritis,

thyroiditis, colitis etc.

• Serum HBV or HCV positive

• Some markers of hepatitis, elevated gamma

globulin or positive anti-nuclear antibodies.
 Schistosomiasis
• Contacting with fresh water contaminated with
cercariae in epidemic area
• Splenomegaly being the earliest and most
prominent sign
• Bleeding from esophageal varices may be the
initial clinical presentation
• Liver function is relatively good
 Alcoholic cirrhosis

• Alcoholic beverage consumption >40~80 g for over

10 years
• Large parotid, myopathy, neuropathy, contraction
of the palmar fascia
• sGOT > sGPT, sGOT/sGPT ratio>2
• Polymorpho-nuclear leukocytosis
 Primary biliary cirrhosis
• Female (90%), middle age (40~60y), Pruritus
before icterus

• Xanthomas Raynaud’s phenomen

sclerodactyly telangiectasis
skin hyperpigmentation

• Elevated AKP, IgM, antimitochondrial antibody

 Wilson’s disease

• Family history of liver or neurologic disease

• Childhood onset
• Kayser-Fleischer corneal rings
• Grossly flapping tremor, spastic gait, other
CNS disorder, osteochondritis
• Low serum ceruloplasmin
 Hemochromatosis

• Positive family history

• Skin pigmentation, diabetes, pseudogout,

cardiomyopathy, loss of body hair, testicular atrophy

• Elevated serum ferritin

 Hepatic function (Child-Pugh
score)
Index Range Score
Neuropathy None 1
I, II 2
III, IV 3
Ascite None 1
Mild 2
Massive 3
Serum bilirubin <2 1
(mg / dl) 2~3 2
>3 3
Serum albumin >3.5 1
(g / dl) 2.8~3.5 2
<2.8 3
Ratio of prothrombin time activity >50 1
30~50 2
<30 3
A: 5~8 scores; B: 9~11 scores; C: 12~15 scores
 Differential diagnosis
• Hepatomegaly

• Ascites

• Complications
Upper GI bleeding
Hepatic encephalopathy
Hepatorenal syndrome
 Hepatomegaly
• Chronic hepatitis

• Primary liver cancer

• Parasitization

• Hemologic diseases (leukemia, lymphoma)

• Metabolic diseases
 Ascites

• Tuberculous peritonitis

• Constrictive pericarditis

• Chronic glumerulonephritis

• Intraperitoneal tumors
 Upper GI bleeding

• Peptic ulcer, acute erosive gastritis, gastric cancer

and esophageal varices are four major sources of
upper GI bleeding

• In cirrhotic patients, bleeding are not entirely due

to varices
 Hepatic encephalopathy

• Hypoglycemia

• Uremia

• Diabetic ketoacidosis

• Nonketonic hyperosmolar syndrome

 Hepatorenal syndrome

• Prerenal azotemia
• Acute tubular necrosis
• Drug nephrotoxicity

• Diagnosis is supported by avid urinary

sodium retention
Urine sodium concentration < 5 mmol / L
unremarkable urinary sediment
 Treatment

• Supportive therapy
• Eliminating the specific causes
• Using antifibrotic drugs
• Management of ascites
• Management of complications
• Liver transplantation
 Supportive therapy
• Appropriate rest
1g protein/kg, 2000 Calories daily
Vitamin(s), thiamine, vitamin K, iron and folic acid
• Removal of exogenous aggravating agents
liver tonics, offending drugs
control of infection and electrolyte
• Correction of hypoalbuminemia and coagulation
fresh frozen plasma, platelet concentrates or
prothrombin complex
Etiology and definitive treatment of cirrhosis
Etiology Treatment
Virus hepatitis ? Antivirals
Schistosomiasis Praziquantel 60~80mg/kg for 2 days
Alcohol Abstention
Iron overload Vensection. Deferoxamine 0.5~1g/kg
Copper overload penicillamine 0.8~1.2 g/day
α1 antitrypsin deficiency ? Transplant
Tyrosinaemia Withdraw dietary tyrosine
Galactosaemia Withdraw milk and milk products
Cholestasis Relieve biliary obstruction
Budd-Chiari syndrome Relieve main venous block
Immunological factors Prednison or predisolon 20~60 mg/day
Toxins and drugs Identify and stop
Cryptogenic ---
 Antifibrotic drugs
• Penicillamine
Primary biliary cirrhosis
Wilson’s disease
Inhibiting the formation of cross-links of collagen

• Colchicine
Inhibiting assembly of collagen
Increasing collagenase production
 Management of ascites
• Ascites with severe, acute liver disease
Improvement of liver function

• Ascites with stable or steadily worsening liver

function
Maximal reabsorption rate: 700~900 ml/day
Goal of management:
weight loss < 1.0kg/day (ascites + peripheral edema)
weight loss < 0.5kg/day (ascites)
 Management of ascites
• Sodium restriction
• Fluid restriction
• Diuresis
• Paracentesis
• Side-to-side portacaval shunt
• Peritoneovenous shunt
• Transjugular intrahepatic portosystemic shunts
(TIPS)
 Sodium restriction
• 1g sodium retaines 200 ml fluid
• > 0.75 g will result in ascites in cirrhotic patients
• < 0.5 g/d (22 mEg), restricted in patients without
ascites

• Strict bed rest

improving renal clearance in the supine position
Fluid restriction

≈1000 ml/day
 Diuresis
• If sodium restriction are failed

• Diuretic for ascites

Urine loss
loop diuretic
Na++ K++ Furosemide
Bumetamide
Distal diuretic
Na+ K Spironolactone
Triamterene
Amiloride
 Diuresis
• Drugs of choice: Spironolactone
Inhibiting aldosterone synthesis
Causing natriuresis with sparing potassium
100mg~400mg/d may induce diuresis
• Furosemide and/or thiazides
both natriuresis and potassium wasting
• Spironolactone(distal diuretic)+Furosemide(loop diuretic)
sufficient to initial diuresis
 Paracentesis
• Paracentesis of 1~2 L of ascitic fluid
effective, less costly

• Albumin or plasma infusion

expensive

• Ascites reinfusion
inexpensive
for refractory or massive ascites
 Portal-systemic shunts

• Side-to-side portacaval shunts

• Peritoneovenous shunts (Le Veen shunt)

• Transjugular intrahepatic portosystemic shunts

(TIPS)
 Management of complications
Variceal bleeding:
• General managements
maintain intravascular volum
close monitoring blood pressure, urine output and
mental status
• Medical managements
use of vasoconstrictors (vasopression or somatostatin)
sclerotherapy
band ligation
beta-adrenergic blockade
 Management of complications

Spontaneous bacterial peritonitis:

• Empirical therapy with cefotoxanine or ampicillin

and an aminoglycoside
• Specific antibiotic therapy are selected
• 10~14 days duration
• Recurrent episodes are high
 Management of complications

Hepatic encephalopathy

Hepatorenal syndrome
Treatment is usually unsuccessful
 Liver transplantation

• Latest advance in management of cirrhosis

• Frequently done in Western country

 Summary
• Definition fibrosis + nodular regeneration
• Viral hepatitis (China) alcohol (Western Country)
• Micro- , Macro- and mixed cirrhosis
• Decompensated stage:
Deterioration of liver function
Portal hypertension
• Complications
• Hepatic function: Child-Pugh score
• Sodium, fluid restriction, diuresis (Spirolactone)