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, esophageal varices, liver failure, and hepatic encephalopathy.
Poor Prognostic Indicators
- Elevated bilirubin and low albumin levels.
- Prolonged prothrombin time and the presence of oedema.