Makindo Medical Notes

Related Subjects: |Chronic liver disease |Cirrhosis |Alkaline phosphatase (ALP) |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Autoimmune Hepatitis |Primary Biliary Cirrhosis |Primary Sclerosing Cholangitis |Wilson disease |Hereditary Haemochromatosis |Alpha-1 Antitrypsin (AAT) deficiency |Non alcoholic steatohepatitis (NASH) |Spontaneous Bacterial Peritonitis |Alcoholism and Alcoholic Liver Disease

Primary Biliary Cirrhosis (PBC) is associated with antimitochondrial antibodies found in 90-95% of cases, with a specificity of 98% for this disease.

About

• PBC involves the progressive autoimmune destruction of small and medium-sized bile ducts, leading to cholestasis and eventual cirrhosis.
• Positive antimitochondrial antibodies (AMAs) are present in 95% of cases, which is highly specific for PBC.

Background

• PBC is a chronic, progressive granulomatous inflammation of the liver.
• It leads to cholestasis, fibrosis, and eventually cirrhosis if left untreated.
• Much more common in females, typically presenting in middle-aged women.
• There is an association with other autoimmune conditions, such as hypothyroidism, Sjögren’s syndrome, and rheumatoid arthritis.

Clinical Features

• Typically affects middle-aged females.
• PBC can be subclinical for years before presenting with overt liver disease signs.
• May be incidentally discovered on blood tests showing a raised ALP (alkaline phosphatase).
• Most common presenting symptoms are lethargy and pruritus (itching).
• As the disease progresses, patients may develop skin pigmentation changes, xanthomas, and xanthelasma.
• Jaundice occurs in the later stages, along with hepatomegaly and splenomegaly.
• Malabsorption of fat-soluble vitamins (A, D, E, K) occurs, leading to deficiencies.

Investigations

• Alkaline phosphatase (ALP) and Gamma-glutamyl transferase (GGT) are elevated, with ALP levels often >1000 IU/L.
• Increased bilirubin and jaundice are late features of the disease.
• Prolonged prothrombin time (PT) due to vitamin K malabsorption and low albumin.
• Raised levels of nonspecific IgM.
• AST and ALT are mildly elevated.
• Hyperlipidemia is common, but interestingly not associated with increased cardiovascular disease risk.
• 98% of patients have a positive anti-mitochondrial antibody, specifically the M2 subtype, targeting the E2 fragment of the pyruvate dehydrogenase complex on the inner mitochondrial membrane.
• Ultrasound shows no extrahepatic obstruction (gallstones, although common in this population, are typically irrelevant in PBC).
• Liver biopsy may show granulomas around proliferating bile ductules with liver fibrosis and cirrhosis, although it has limited prognostic value.

Management

• Ursodeoxycholic acid is the first-line treatment. It helps to relieve itching and may slow disease progression by improving bile acid excretion and reducing intestinal bile acid reabsorption.
• No role for immunosuppressive drugs such as steroids, colchicine, azathioprine, or methotrexate (all have been proven ineffective).
• Patients should receive vitamin supplementation (A, D, E, K) and have their nutrition optimized to address deficiencies.
• The onset of jaundice is a poor prognostic sign, often indicating a prognosis of fewer than two years without intervention.
• Liver transplantation is an option for patients with advanced disease, and outcomes are generally excellent.
• Complications include portal hypertension, oesophageal varices, liver failure, and hepatic encephalopathy.

Poor Prognostic Indicators

• Elevated bilirubin and low albumin levels.
• Prolonged prothrombin time and the presence of oedema.