Liver disease

Introduction
Liver disease is a broad term encompassing conditions that impair liver structure or function. The liver is a vital organ responsible for metabolism, detoxification, synthesis of proteins and clotting factors, and bile production. Liver diseases can be acute or chronic, and they may result from infections, toxins, autoimmune processes, metabolic disorders, or genetic defects. Severe and progressive liver disease can lead to liver failure, portal hypertension, and death.

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Major Types of Liver Disease

1. Infectious Causes

   • Viral hepatitis (A, B, C, D, E)

   • Parasitic infections (schistosomiasis, liver flukes)

2. Alcohol-related Liver Disease (ARLD)

   • Spectrum: fatty liver (steatosis) → alcoholic hepatitis → cirrhosis.

3. Non-Alcoholic Fatty Liver Disease (NAFLD) / Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD)

   • Associated with obesity, type 2 diabetes, metabolic syndrome.

   • Progresses to non-alcoholic steatohepatitis (NASH/MASH) and cirrhosis.

4. Autoimmune Liver Diseases

   • Autoimmune hepatitis.

   • Primary biliary cholangitis (PBC).

   • Primary sclerosing cholangitis (PSC).

5. Drug-Induced Liver Injury (DILI)

   • Acetaminophen (paracetamol) toxicity (common cause of acute liver failure).

   • Amoxicillin-clavulanate, methotrexate, isoniazid, valproate, statins.

6. Genetic / Metabolic Disorders

   • Hemochromatosis (iron overload).

   • Wilson’s disease (copper accumulation).

   • Alpha-1 antitrypsin deficiency.

7. Malignancies

   • Hepatocellular carcinoma (HCC).

   • Cholangiocarcinoma.

   • Metastatic liver disease.

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Clinical Features

General Symptoms

• Fatigue.

• Anorexia, nausea, vomiting.

• Weight loss.

• Abdominal discomfort.

Signs of Acute Disease

• Jaundice (yellowing of skin and sclera).

• Dark urine, pale stools.

• Right upper quadrant tenderness.

Signs of Chronic Liver Disease / Cirrhosis

• Spider angiomas.

• Palmar erythema.

• Gynecomastia, testicular atrophy (in men).

• Ascites.

• Splenomegaly.

• Peripheral edema.

• Hepatic encephalopathy (confusion, asterixis).

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Complications of Advanced Liver Disease

• Portal hypertension → variceal bleeding.

• Ascites → spontaneous bacterial peritonitis.

• Hepatorenal syndrome.

• Hepatocellular carcinoma.

• Coagulopathy and bleeding tendency.

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Diagnosis

Laboratory Tests

• Liver function tests (ALT, AST, ALP, GGT, bilirubin).

• Albumin and prothrombin time/INR (synthetic function).

• Viral hepatitis serology.

• Autoantibodies (ANA, SMA, AMA, p-ANCA).

• Iron studies, ceruloplasmin, alpha-1 antitrypsin levels.

Imaging

• Ultrasound (first-line).

• CT or MRI for tumor detection or advanced disease.

• Transient elastography (FibroScan) for fibrosis assessment.

Histology

• Liver biopsy for definitive diagnosis and staging in selected cases.

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Management

General Measures

• Treat underlying cause.

• Avoid alcohol and hepatotoxic drugs.

• Balanced nutrition with adequate protein intake unless encephalopathy present.

• Vaccinate against hepatitis A and B if non-immune.

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1. Viral Hepatitis

Hepatitis B

• Tenofovir disoproxil fumarate: 300 mg orally once daily.

• Entecavir: 0.5 mg orally once daily (1 mg if lamivudine-resistant).

Hepatitis C

• Direct-acting antiviral combinations:

  • Sofosbuvir 400 mg + Velpatasvir 100 mg orally once daily for 12 weeks.

  • Glecaprevir 300 mg + Pibrentasvir 120 mg orally once daily for 8–12 weeks.

Hepatitis A and E

• Supportive care; no specific antiviral therapy.

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2. Alcohol-related Liver Disease

• Absolute alcohol abstinence.

• Prednisolone 40 mg orally daily for 28 days in severe alcoholic hepatitis (Maddrey score ≥32).

• Nutritional support, including thiamine supplementation.

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3. Non-Alcoholic Fatty Liver Disease (NAFLD/MASLD)

• Lifestyle changes: weight loss (target 7–10%), exercise.

• Pioglitazone 15–45 mg daily (for NASH in type 2 diabetes; specialist use).

• Vitamin E 800 IU daily (for non-diabetic NASH; specialist use).

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4. Autoimmune Hepatitis

• Prednisolone: start with 30–60 mg daily, taper gradually.

• Azathioprine 1–2 mg/kg/day as a steroid-sparing agent.

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5. Primary Biliary Cholangitis (PBC)

• Ursodeoxycholic acid 13–15 mg/kg/day in divided doses lifelong.

• Obeticholic acid 5–10 mg daily if inadequate response to ursodiol.

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6. Primary Sclerosing Cholangitis (PSC)

• No proven curative medical therapy; symptomatic management.

• Endoscopic therapy for dominant strictures.

• Liver transplantation in advanced disease.

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7. Hemochromatosis

• Therapeutic phlebotomy (weekly until ferritin normalizes, then maintenance every 2–4 months).

• Avoid iron supplements and excess vitamin C.

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8. Wilson’s Disease

• Penicillamine: 250 mg orally four times daily (gradually increased).

• Trientine: 250–500 mg orally two to four times daily.

• Zinc acetate: 25–50 mg elemental zinc orally three times daily to reduce copper absorption.

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9. Hepatic Encephalopathy

• Lactulose: 30–45 mL orally every 1–2 hours until 2–3 soft stools daily, then maintenance.

• Rifaximin 550 mg orally twice daily (as add-on in recurrent cases).

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10. Variceal Bleeding Prevention

• Propranolol: 20–40 mg orally twice daily (titrate to reduce heart rate by ~25%).

• Endoscopic variceal ligation in high-risk varices.

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11. Hepatocellular Carcinoma (HCC)

• Surgical resection or liver transplantation if eligible.

• Local ablation or transarterial chemoembolization (TACE) for non-surgical candidates.

• Sorafenib 400 mg orally twice daily or Lenvatinib 8–12 mg daily for advanced disease.

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Liver Transplantation

• Indicated for end-stage liver disease, acute liver failure unresponsive to medical therapy, or unresectable early-stage HCC.

• Requires lifelong immunosuppression (e.g., tacrolimus, cyclosporine).

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Prognosis

• Highly variable depending on cause, stage at diagnosis, and treatment adherence.

• Early detection and targeted therapy improve outcomes.

• Advanced cirrhosis carries high morbidity and mortality without transplantation.