Primary Biliary Cholangitis: Symptoms, Stages, And Diagnosis
Primary biliary cholangitis (PBC) is a chronic progressive liver disease characterized by the accumulation of bile due to damage in the small bile ducts within the liver. The condition involves non-suppurative inflammation of intrahepatic bile ducts, leading to bile duct destruction, portal tract inflammation, and gradual liver scarring. If left untreated, it can progress to cirrhosis over time.
PBC predominantly affects middle-aged women, with approximately 90% of cases occurring in females between the ages of 40 and 55. The onset of the disease is often subtle, and symptoms may develop gradually. Below are the key clinical manifestations associated with PBC.
1. Chronic fatigue is one of the most common early symptoms experienced by patients, often appearing even before significant liver damage occurs.
2. Skin itching (pruritus) is another frequent symptom, varying in severity among individuals. It is believed to be related to the deposition of bile acids in the skin.
3. Jaundice, or yellowing of the skin and eyes, typically appears months or years after the initial onset of the disease. This obstructive jaundice indicates substantial damage to the bile ducts. While deeper or rapidly progressing jaundice suggests worsening disease, many patients may not develop jaundice at all.
4. Digestive issues such as bloating, loss of appetite, and belching may occur due to impaired liver function.
5. As the disease progresses, fat malabsorption (steatorrhea) may develop, especially in the presence of long-standing jaundice. This can lead to deficiencies in fat-soluble vitamins like A and D. Vitamin A deficiency can cause vision problems, while vitamin D deficiency may result in metabolic bone disease, including osteoporosis or osteomalacia, which presents with bone pain and increased risk of fractures.
6. Skin xanthomas, or fatty deposits under the skin, can appear due to elevated cholesterol levels commonly seen in PBC patients.
7. Enlarged liver and spleen (hepatosplenomegaly) are also frequently observed.
8. In advanced stages, complications of cirrhosis arise, including portal hypertension and esophageal varices. The clinical progression of PBC is typically divided into four phases: asymptomatic phase with normal liver function, abnormal liver function phase, symptomatic phase, and decompensated phase.
In terms of laboratory findings, early PBC is marked by signs of cholestasis — elevated serum bilirubin levels, along with significantly increased alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), indicating bile duct injury. However, bilirubin levels may remain normal during the early stages. Serum transaminases may be mildly elevated or within normal limits. Cholesterol and lipoprotein levels are often elevated, while albumin remains stable in early disease. Immunoglobulins, particularly IgM, show a characteristic increase. Other autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), and anti-thyroid antibodies may also be present.
One of the most important diagnostic markers for PBC is the presence of anti-mitochondrial antibodies (AMA), which are detected in over 90% of cases. The M2 subtype of AMA is highly specific for PBC and plays a crucial role in diagnosing both symptomatic and asymptomatic patients.
The histological progression of PBC is classified into four stages:
-Stage 1- Portal Cholangitis: Characterized by chronic non-suppurative inflammation of interlobular or septal bile ducts, with infiltration of lymphocytes, plasma cells, histiocytes, and occasional eosinophils in the portal areas. Granulomas may be present, but liver architecture remains intact without bile stasis.
- Stage 2 – Bile duct proliferation: Small bile ducts proliferate while interlobular ducts disappear. Portal inflammation extends around bile ducts (periductal inflammation), and cholestasis becomes evident in periductal hepatocytes. Ultrastructural changes include dilated bile canaliculi, loss of microvilli, and mitochondrial swelling.
- Stage 3 – Fibrosis: Inflammation subsides, leaving behind fibrous scars that extend from one portal area to another or into the lobule. Bile retention worsens.
- Stage 4 – Cirrhosis: Focal hepatic necrosis and extensive fibrosis lead to the formation of regenerative nodules and pseudolobules. Vascular distortion occurs as fibrous septa connect portal regions.
Understanding the clinical features, serological markers, and histological changes is essential for timely diagnosis and management of primary biliary cholangitis.