Discuss the aetiology, clinical features, complications, investigations and management of cirrhosis of the liver.

Definition

Cirrhosis is the end stage of chronic liver injury, characterised histologically by diffuse hepatic fibrosis with conversion of normal architecture into structurally abnormal regenerative nodules. The two consequences that produce all its clinical features are hepatocellular failure and portal hypertension.

It is described as compensated (asymptomatic, often detected incidentally) or decompensated (with ascites, variceal bleeding, encephalopathy or jaundice) — a distinction that dominates prognosis, since decompensation marks a sharp fall in survival.

Aetiology

• Alcohol — a leading cause worldwide and in India.
• Chronic viral hepatitis B and C.
• Non-alcoholic fatty liver disease (NAFLD/NASH) — now the fastest-growing cause, tracking the epidemic of obesity and type 2 diabetes in India.
• Autoimmune — autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis.
• Metabolic and genetic — Wilson's disease, haemochromatosis, alpha-1 antitrypsin deficiency, galactosaemia, glycogen storage disease.
• Biliary — secondary biliary cirrhosis from prolonged obstruction.
• Vascular — Budd–Chiari syndrome, right heart failure and constrictive pericarditis (cardiac cirrhosis), veno-occlusive disease.
• Drugs and toxins — methotrexate, amiodarone, isoniazid.
• Cryptogenic — many now recognised to be burnt-out NASH.

Clinical Features

Symptoms: fatigue, anorexia, weight loss, muscle wasting, abdominal distension, ankle swelling, easy bruising, pruritus, and reduced libido.

Signs of chronic liver disease:

Note: many signs reflect hyperoestrogenism from impaired hepatic metabolism — spider naevi, palmar erythema, gynaecomastia, testicular atrophy and body hair loss.

COMPLICATIONS — the substance of clinical hepatology

1. Portal hypertension → oesophageal and gastric varices with bleeding, splenomegaly with hypersplenism, caput medusae.

2. Ascites → spontaneous bacterial peritonitis, hepatic hydrothorax, umbilical hernia.

3. Hepatic encephalopathy.

4. Hepatorenal syndrome.

5. Hepatopulmonary syndrome (hypoxia with intrapulmonary shunting, platypnoea and orthodeoxia) and portopulmonary hypertension.

6. Coagulopathy — reduced synthesis of clotting factors and thrombocytopenia; note that cirrhosis is a state of rebalanced haemostasis, not simple anticoagulation, and thrombosis also occurs.

7. Hepatocellular carcinoma.

8. Malnutrition and sarcopenia; osteoporosis; cirrhotic cardiomyopathy; increased susceptibility to infection.

Investigations

• Liver function tests: AST and ALT may be normal or only mildly raised in established cirrhosis — normal transaminases do not exclude it. Low albumin, raised bilirubin and prolonged INR reflect synthetic failure. An AST:ALT ratio > 2 suggests alcoholic liver disease.
• CBC — thrombocytopenia is the earliest and most useful haematological clue (hypersplenism and reduced thrombopoietin); anaemia, leucopenia.
• Ultrasound — coarse echotexture, nodular surface, shrunken right lobe with caudate lobe hypertrophy, splenomegaly, ascites, portal vein diameter and flow on Doppler, and screening for focal lesions.
• Transient elastography (FibroScan) and serum fibrosis scores (FIB-4, APRI) — non-invasive assessment of fibrosis, now largely replacing biopsy for staging.
• Upper GI endoscopy — to screen for and grade varices.
• Ascitic fluid analysis with SAAG (see the ascites answer).
• Aetiological workup: viral serology, autoantibodies (ANA, ASMA, AMA) with immunoglobulins, serum caeruloplasmin and 24-hour urinary copper (Wilson's — mandatory under 40), ferritin and transferrin saturation (haemochromatosis), alpha-1 antitrypsin.
• Liver biopsy — for uncertain aetiology; less often needed now.
• Hepatocellular carcinoma surveillance: 6-monthly ultrasound with or without alpha-fetoprotein in all cirrhotics.

Prognostic scores: Child–Turcotte–Pugh (bilirubin, albumin, INR, ascites, encephalopathy — classes A, B, C) and MELD (bilirubin, INR, creatinine, sodium), which determines transplant priority.

Management

1. Treat the cause — the only intervention that can halt or reverse progression

• Absolute alcohol abstinence with structured support
• antiviral therapy for hepatitis B and C (cure of hepatitis C can produce regression of fibrosis)
• weight loss and metabolic control in NAFLD
• immunosuppression in autoimmune hepatitis
• chelation in Wilson's disease
• venesection in haemochromatosis.

2. General measures

• Nutrition — adequate calories and protein (protein restriction is obsolete and harmful), with late-evening snacks to reduce catabolism; salt restriction for ascites; supplement fat-soluble vitamins, thiamine and zinc.
• Avoid hepatotoxins — alcohol, NSAIDs (which precipitate renal failure and bleeding), aminoglycosides, and unregulated herbal and traditional preparations, which are a significant and under-recognised cause of liver injury in India.
• Vaccinate against hepatitis A and B, influenza and pneumococcus.
• Screen for and treat osteoporosis; treat pruritus (cholestyramine).

3. Manage complications

• Varices: non-selective beta-blockers (propranolol, carvedilol) or endoscopic band ligation for primary prophylaxis; band ligation, vasoactive drugs, antibiotics and TIPS for bleeding (see the upper GI bleed answer).
• Ascites: salt restriction, spironolactone with furosemide, therapeutic paracentesis with albumin cover.
• Spontaneous bacterial peritonitis: diagnostic tap, antibiotics, albumin, secondary prophylaxis.
• Encephalopathy: lactulose and rifaximin; identify precipitants.
• Hepatorenal syndrome: terlipressin with albumin.
• Hepatocellular carcinoma: surveillance, and treatment by stage.

4. Liver transplantation — the definitive treatment for decompensated cirrhosis and for selected hepatocellular carcinoma; referral should be made before the patient becomes too ill, and requires demonstrated abstinence in alcohol-related disease.