Cirrhosis

Cirrhosis is a chronic liver disease characterised by replacement of normal liver tissue by scar tissue. It’s the irreversible end-stage of hepatitis which cause significant morbidity and mortality. There is continuous loss of functional liver tissue, which is initially compensated and asymptomatic as the remaining liver can compensate. However, acute insults precipitate decreases in liver function, causing hepatic decompensation and development of dramatic and life-threatening complications. Cirrhosis is also an important risk factor for hepatocellular carcinoma.

Cirrhosis is a common condition worldwide.

Etiology

• Alcoholic liver disease
• Metabolic associated fatty liver disease
• Chronic viral hepatitis (C, B or D)
• Haemochromatosis
• Biliary obstruction (primary biliary cholangitis, primary sclerosing cholangitis)
• Autoimmune hepatitis
• Wilson disease
• Heart failure
• Alpha-1 antitrypsin deficiency

The most common causes in the Western world are alcoholic liver disease and metabolic associated fatty liver disease.

The following triggers may cause hepatic decompensation:

• Infection
• Alcohol use
• Hypovolaemia (bleeding or dehydration)

Classification

The liver function or cirrhosis severity can be classified according to the Child-Pugh or MELD scores. The latter is mostly used in the context of transplantation. The Child-Pugh score scores cirrhosis mortality based on:

• Bilirubin level
• Albumin level
• INR
• Ascites
• Encephalopathy

Pathology

Continous necrosis and regeneration of the liver parenchyme replaces the functioning liver parenchyme with fibrosis. The pattern of fibrosis eventually forms fibrous septa. The more prominent they become, the more the liver takes on a nodular cirrhotic appearance. Histology shows pseudolobules separated by fibrosis. These pseudolobules can be distinguished from hepatic lobules by the fact that they don’t have a central vein.

The liver will now be a brown, shrunken, nonfatty organ composed of cirrhotic nodules.

We can distinguish multiple types of cirrhosis:

• Micronodular cirrhosis (Laennec cirrhosis) – caused by alcoholism
• Macronodular cirrhosis – caused by chronic hepatitis B or C or by autoimmune hepatitis
• Pigment cirrhosis – Caused by hemochromatosis (iron accumulation) or Wilson disease (copper accumulation)
• Biliary cirrhosis – Caused by damage to the biliary tree

Clinical features

As long as there remains enough functional liver to compensate for the cell loss, the condition is known as compensated cirrhosis and is mostly asymptomatic. It may cause nonspecific symptoms like anorexia, weight loss, asterixis, malabsorption, muscle cramps, and fatigue.

Decompensation occurs when the liver function worsens due to an acute insult, or in end-stage cirrhosis where there is too little functional liver tissue left. This can cause a variety of symptoms and complications:

• Jaundice
• Pruritus
• Upper GI bleeding (from variceal bleeding)
• Ascites
• Hepatic encephalopathy
• Spontaneous bacterial peritonitis
• Hepatocellular carcinoma
• Hepatorenal syndrome
• Hepatopulmonary syndrome

Physical examination may reveal:

• Telangiectasia
• Caput medusae
• Hepatomegaly
• Splenomegaly
• Features of hyperoestrogenism (gynaecomastia, hypogonadism)

Complications not considered to be a sign of decompensation:

• Portal vein thrombosis
• Cardiomyopathy
• Coagulopathy -> excessive bleeding

In end-stage cirrhosis there is collapse of liver functions, causing liver failure with severe and refractory decompensation symptoms.

Diagnosis and evaluation

Diagnosis of cirrhosis can usually be made based on clinical features, ultrasound, and special non-invasive investigations like FibroScan, transient elastography (TE) and acoustic radiation force impulse (ARFI). Ultrasound shows a shrunk liver with nodular surface and loss of homogeneity.

Typical laboratory findings of cirrhosis include:

• Elevated AST, ALT
• Elevated INR – due to decreased production of coagulation factors
• Hypoproteinaemia and hypoalbuminaemia
• Thrombocytopaenia
• Macrocytic anaemia

Determination of the etiology is based on patient history as well as laboratory examination:

• Viral hepatitis serology
• Alpha-1 antitrypsin – for deficiency
• Autoantibodies and hypergammaglobulinaemia – for autoimmune hepatitis
• Iron studies – for haemochromatosis
• Copper studies – for Wilson disease

Histology is the gold standard for the evaluation of cirrhosis, but it’s not usually required for the diagnosis.

Treatment

Management of cirrhosis involves preventing and treating complications. This also involves regular surveillance for worsening of the cirrhosis, and for development of hepatocellular carcinoma (by regular ultrasound (every 6 months) and monitoring of AFP).

To prevent triggers of decompensation, avoidance of hepatotoxic substances (including alcohol), as well as routine vaccinations, are important. Hepatic decompensation is usually self-limiting, but an episode of decompensation increases the risk for further episodes and complications later.

To avoid catabolic state, which could precipitate hepatic encephalopathy, it’s important to achieve sufficient energy and protein intake, ~80 – 100g protein and ~3000 Kcal/day, to avoid deficiency. Enteral nutrition should be added if patient cannot achieve this by regular foods.

Other important treatments for complications of cirrhosis include:

• Propranolol – decreases portal hypertension and the risk of variceal bleeding
• Ligation – to decrease the risk of variceal bleeding
• Transjugular intrahepatic portosystemic shunt (TIPS) – in case of persistent or recurrent upper GI bleeding due to portal hypertension, or ascites.
• Sodium restriction, fluid restriction, diuretics (MRA or loop) – in case of ascites
• Antibiotics – for spontaneous bacterial peritonitis
• Lactulose ± rifaximin – for hepatic encephalopathy
• Fresh frozen plasma – for coagulopathy

Liver transplantation is the only curative treatment for cirrhosis. It’s indicated for all cases of cirrhosis where decompensation has developed.