Liver Cirrhosis
Liver Cirrhosis
Liver Cirrhosis
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
Viral hepatitis
HBV HCV HAV HEV
HBV + HDV
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 eastern and southern Europe parts of central Asia
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.
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
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
Metabolic abnormality
Iron storage disease (Hemochromatosis)
Malnutrition
Chronic inflammatory bowel disease
Cryptogenic cirrhosis
Etiology is unknown
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
Micronodular
Micronodular cirrhosis
Features: Thick regular septa Regenerating small nodules (<3mm) Involvement of every lobule
Macronodular cirrhosis
Features: Septa Nodules of variable size (>3mm, even 1~ 3 cm) Normal lobules in the large nodules
Macronodular cirrhosis
Postnecrotic type: Coarsely scarred liver Large nodules surrounded by broad fibrous septa Clumping togathered numerous portal trials
Macronodular cirrhosis
Posthepatitic type: Macronodules separated by slender fibrous strands Connect individual portal areas to each other Viral hepatitis Wilsons disease
Mixed cirrhosis
Features:
Presenting both micro- and macronodules
Clinical manifestation
Onset: Cryptical and slowly progressive Majority: 3~5 years or 10 years Minority: 3~6 months
Compensated stage
Fatigue Loss of appetite Anorexia Abdominal discomfort Abdominal pain
Hepatomegaly (slightly or moderately) Splenomegaly
Decompensated stage
Deterioration of liver function
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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
Liver
Early stage Enlarged and palpable firm regular edge a fine to coarsely nodular surface Later stage Shrunk and impalpable
Splenomegaly
Portal-systemic collaterals
Esophageal and gastric varices
Splenomegaly
Slightly or moderatory enlarged
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
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Complications
Upper gastrointestinal bleeding Hepatic encephalopathy Infection Hepatorenal syndrome Primary liver cancer Imbalance of electrolytes and acid-alkaline
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
Infection
Increased risk for bacterial infection
pneumonia biliary infection E.coli infection and spontaneous bacterial peritonitis (SBP)
SBP
Pathogen of SBP: grams negative bacteria
Features of SBP:
fever, abdominal pain or tenderness
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)
Hyponatraemia Hypokalaemia
Metabolic alkalosis
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
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
Wilsons 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
Range
None I, II III, IV None Mild Massive
Score
1 2 3 1 2 3
Ascite
Serum bilirubin
(mg / dl)
1 2 3
1 2 3 1 2 3
Serum albumin
(g / dl)
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
to varices
Hepatic encephalopathy
Hypoglycemia Uremia
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
Antifibrotic drugs
Penicillamine Primary biliary cirrhosis Wilsons disease Inhibiting the formation of cross-links of collagen
Colchicine
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
Fluid restriction
1000 ml/day
Diuresis
If sodium restriction are failed Diuretic for ascites
Urine loss loop diuretic Na++
K++
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
expensive
Ascites reinfusion
Portal-systemic shunts
Side-to-side portacaval shunts
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
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
Liver transplantation
Latest advance in management of cirrhosis
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)