Cirrhosis of Liver

Physical Examination

General Examination:

• Signs of hepatic encephalopathy, including asterixis (liver flap).

• Dupuytren's contracture in hands, indicating chronic liver disease.

• Spider naevi on arms, typically more than five suggesting liver disease.

• Sparse axillary hair

• Fetor hepaticus (musty smell of breath), due to hepatic encephalopathy.

• Clubbing, Palmar erythema found in the hands.

• Leukonychia (white nails)

• Jaundice, indicative of severe liver disease.

• In advanced stages, gynaecomastia may be present due to hormonal changes.

Inspection:

• Distended abdomen due to ascites.

• Caput medusae, dilated veins around the umbilicus due to portal hypertension.

• Visible liver pulsation if there is a concurrent cardiac failure.

Palpation:

• Hepatomegaly - enlarged liver may be palpable, often with a hard, irregular edge in cirrhosis.

• Splenomegaly, suggesting portal hypertension.

• If ascites is present, it may be possible to feel a fluid wave or shifting dullness.

Percussion:

• Dullness in flanks if ascites is present.

• Possibly enlarged liver and/or spleen.

Auscultation:

• A hepatic bruit may be heard over the liver in hepatocellular carcinoma

• Absence of normal bowel sounds might indicate paralytic ileus or peritonitis.

Additional Examination:

• Digital rectal examination for signs of gastrointestinal bleeding, as this may occur with esophageal varices.

• Testicular atrophy in male and breast atrophy in female

Signs of the underlying cause of chronic liver disease

• Alcohol-related Cirrhosis: Signs of chronic alcohol use such as Dupuytren's contracture, parotid enlargement, palmar erythema, spider naevi, and gynecomastia.

• Viral Hepatitis: In chronic hepatitis B and C, you may also notice signs of injecting drug use and tattoo marks

• Autoimmune Hepatitis: Other signs of autoimmunity could be present, such as vitiligo, thyroid disease, rheumatoid arthritis, or type 1 diabetes.

• Hemochromatosis: Bronze diabetes (hyperpigmentation and diabetes), arthritis, and signs of heart failure may be present.

• Wilson's Disease: Kayser-Fleischer rings in the eyes, neuropsychiatric symptoms, and signs of liver disease.

• Primary Biliary Cirrhosis: Xanthelasma (yellowish patches around the eyes) or xanthomas (fatty deposits under the skin), pruritus marks from scratching due to the bile acid deposition in the skin.

• Non-Alcoholic Steatohepatitis (NASH): Signs of metabolic syndrome including central obesity, hypertension, dyslipidemia (xanthelasma, xanthoma), and type II diabetes (finger prick marks)

Investigations

Laboratory Tests:

• Routine blood tests

  • Full Blood Count: To check for anaemia, thrombocytopenia (suggesting hypersplenism), and leukopenia.

  • Liver Function Tests: To assess the severity of liver disease and patterns of liver injury (cholestatic, hepatocellular).

  • Coagulation Profile (PT/INR): Prolongation may indicate a decrease in the liver's synthetic function.

  • Serum Albumin: Low levels indicate decreased liver synthesis.

• For underlying condition

  • Viral Hepatitis Serology: To identify hepatitis B or C as a potential cause.

  • Autoantibodies: Including ANA, ASMA, and anti-LKM to identify autoimmune hepatitis.

  • Serum Iron, Ferritin, Transferrin Saturation: To detect hemochromatosis.

  • Alpha-1 Antitrypsin Levels: To exclude alpha-1 antitrypsin deficiency.

  • Ceruloplasmin and Urinary Copper: To rule out Wilson's disease.

  • AMA: To detect primary biliary cirrhosis.

  • Serum Immunoglobulins: IgG may be elevated in autoimmune hepatitis, IgM in primary biliary cirrhosis.

  • Lipid Profile: Altered lipid profile may suggest Non-Alcoholic Fatty Liver Disease (NAFLD) or Non-Alcoholic Steatohepatitis (NASH).

• For complication

  • Alpha-fetoprotein (AFP) Test: Hepatocellular carcinoma

• Imaging:

  • Ultrasound Abdomen: To assess liver size, echotexture, evidence of portal hypertension, or focal liver lesions.

  • Doppler Ultrasound: To assess blood flow in hepatic vessels and rule out Budd-Chiari syndrome.

  • CT/MRI: More detailed liver structure, biliary tract anatomy, and hepatic vasculature.

• Invasive Tests:

  • Liver Biopsy: Can help identify the specific cause and stage of liver disease.

  • Endoscopy: To screen for esophageal or gastric varices.

• Other Tests:

  • Ascitic Fluid Analysis: If ascites are present, an analysis can help differentiate between portal hypertension-related and other causes.

  • ECG and Chest X-ray: To evaluate for cardiac causes of liver congestion.

Management

General Management:

• Multidisciplinary team approach involving hepatologists, surgeons, nurses, dietitians, social workers, and mental health professionals.

• Mental health assessment and management, as depression and anxiety, are common in people with chronic illness

• Counsel the patient about the nature of the disease and the importance of regular monitoring and treatment compliance.

• Lifestyle modifications such as alcohol abstinence, weight loss for those with non-alcoholic fatty liver disease (NAFLD), healthy diet, and regular exercise.

• Regular surveillance for complications such as portal hypertension, hepatocellular carcinoma, and hepatic encephalopathy.

• Vaccinations against hepatitis A and B, influenza, and pneumococcal pneumonia, if not immune or vaccinated.

Medical Management:

• Treat the underlying cause of liver disease

  • Antiviral therapy for viral hepatitis, corticosteroids for autoimmune hepatitis, chelating agents for hemochromatosis, ursodeoxycholic acid for primary biliary cirrhosis.

• Manage complications:

  • Diuretics, sodium restriction, and paracentesis for ascites.

  • Propranolol or nadolol for primary prophylaxis of variceal bleeding.

  • Lactulose and rifaximin for hepatic encephalopathy.

  • Albumin and vasoconstrictors (like terlipressin) for hepatorenal syndrome.

• Address nutritional deficiencies and malnutrition.

• Supplement with fat-soluble vitamins (A, D, E, K) if required.

Surgical Management:

• Consider liver transplantation for patients with decompensated cirrhosis or hepatocellular carcinoma

• Transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites or variceal bleeding not responsive to medical therapy.

• Endoscopic band ligation for esophageal varices at risk of bleeding.

Other:

• Regular screening for hepatocellular carcinoma with ultrasound and alpha-fetoprotein levels every 6 months for those at risk.

• Palliative care involvement for symptom management and end-of-life care in advanced disease.

Causes of chronic liver disease

• Alcoholic Liver Disease: Chronic alcohol abuse can cause alcoholic hepatitis, and, ultimately cirrhosis.

• Viral Hepatitis: Hepatitis B and C are common viral causes of chronic liver disease

• Non-alcoholic Fatty Liver Disease (NAFLD): This is related to obesity, type 2 diabetes, and metabolic syndrome. It can progress to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis.

• Autoimmune Hepatitis: This is a chronic condition characterised by immune-mediated liver inflammation. It can progress to cirrhosis if left untreated.

• Chronic Cholestatic Diseases: Includes primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

• Genetic Disorders: Hemochromatosis (iron overload), Wilson's disease (copper overload), and alpha-1 antitrypsin deficiency

• Drug-Induced Liver Injury: Some medications, such as methotrexate and amiodarone can cause chronic liver damage and cirrhosis, especially when taken in large amounts or for a long time.

• Hepatic Vascular Diseases: Conditions such as Budd-Chiari syndrome (hepatic vein thrombosis) and non-cirrhotic portal hypertension can lead to chronic liver disease.

Features of chronic liver disease

• Jaundice: Yellowing of the skin and sclera due to elevated bilirubin levels.

• Ascites: Accumulation of fluid in the peritoneal cavity, often presenting with abdominal distension.

• Spider naevi: These are vascular lesions that occur predominantly on the upper body and face.

• Palmar erythema: Reddening of the palms, particularly the thenar and hypothenar eminences.

• Dupuytren's contracture: Thickening of the tissue underneath the skin of the palm and fingers.

• Gynaecomastia and testicular atrophy: Hormonal imbalances can lead to breast enlargement in men and shrinking of the testicles.

• Caput medusae: Dilated veins around the umbilicus due to portal hypertension.

• Splenomegaly: Enlarged spleen due to portal hypertension.

• Hepatic encephalopathy: Altered mental status, confusion, asterixis (flapping tremor), and in severe cases, coma.

• Fetor hepaticus: Musty or sweet breath odour due to volatile substances that the damaged liver cannot break down.

• Bruising and bleeding: Due to coagulopathy associated with liver disease.

• Asterixis: A "flapping tremor" often associated with hepatic encephalopathy.

Complications of chronic liver disease

• Portal Hypertension: This is increased pressure in the portal venous system and can lead to complications such as ascites, varies, and hepatic encephalopathy.

• Ascites: Fluid accumulation in the peritoneal cavity, typically due to portal hypertension and hypoalbuminemia. Can lead to spontaneous bacterial peritonitis (SBP) if infected.

• Varices: Dilated blood vessels, particularly in the oesophagus and stomach, due to portal hypertension. They have a risk of rupture and bleeding, a life-threatening event.

• Hepatic Encephalopathy: A spectrum of neuropsychiatric abnormalities caused by the accumulation of toxins (like ammonia) in the brain, which the liver is unable to detoxify.

• Coagulopathy: The liver synthesises clotting factors, so chronic liver disease can lead to coagulation abnormalities and increased bleeding risk.

• Hepatorenal Syndrome: A type of acute kidney injury that occurs in advanced chronic liver disease, particularly with ascites.

• Hepatopulmonary Syndrome: Lung-related complications that can cause dyspnea and hypoxemia.

• Hepatocellular Carcinoma (HCC): Chronic liver disease, especially cirrhosis, significantly increases the risk of developing liver cancer.

• Malnutrition: Particularly in advanced disease, malabsorption and altered metabolism can lead to malnutrition and muscle wasting.

Child-Pugh score

The Child-Pugh score is a commonly used system for assessing the severity of chronic liver disease, primarily cirrhosis. It helps to predict mortality risk, need for liver transplantation, and prognosis.

The Child-Pugh score includes five clinical measures, each of which can score 1-3 points. A lower score indicates a less severe disease.

Total Bilirubin:

1 point: ≤ 34 μmol/L (2 mg/dL)

2 points: 34–50 μmol/L (2-3 mg/dL)

3 points: > 50 μmol/L (3 mg/dL)

Serum Albumin:

1 point: > 35 g/L

2 points: 28–35 g/L

3 points: < 28 g/L

INR (International Normalized Ratio):

1 point: ≤ 1.7

2 points: 1.71–2.20

3 points: > 2.20

Ascites:

1 point: None

2 points: Mild (diuretic-responsive)

3 points: Moderate to severe (diuretic-resistant)

Hepatic Encephalopathy:

1 point: None

2 points: Grade I-II (or suppressed with medication)

3 points: Grade III-IV (or refractory)

The Child-Pugh classification is:

Class A: 5-6 points (compensated disease)

Class B: 7-9 points (significant functional compromise)

Class C: 10-15 points (decompensated disease)

Patients with a higher Child-Pugh class have a worse liver function, poorer prognosis, and a higher risk of mortality. The score also guides the management and treatment approach, including candidacy for liver transplantation.

Antibodies in chronic liver disease

Primary Biliary Cholangitis (PBC): Antimitochondrial antibodies (AMAs), particularly the M2 subtype, is detected in about 98% of cases. Serum immunoglobulin M (IgM) levels are typically elevated.

Primary Sclerosing Cholangitis (PSC): Autoantibodies such as antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) may be positive.

Autoimmune Hepatitis (AIH): Anti-smooth muscle antibodies (ASMA), anti-liver/kidney microsomal type 1 antibody (Anti-LKM1), and occasionally antinuclear antibodies (ANA) may be positive.

Precipitating factors of hepatic encephalopathy

• Infection, especially SBP

• Upper GI bleeding

• Electrolytes imbalance: hypokalaemia, hyponatremia

• Hypoglycemia

• Protein excess

• Constipation

• Dehydration

• Drugs: sedatives, diuretics

• TIPS