The course of primary biliary cholangitis (PBC), a chronic disease that destroys the small bile ducts of the liver, varies widely between patients: some remain well for many years, while others progress to cirrhosis and its complications.
Natural history
About half of patients are asymptomatic when the disease is found, and how they do depends partly on whether they start asymptomatic. Patients who are initially asymptomatic — anti-mitochondrial antibody (AMA) positive at a titre of 1:40 or greater, negative biochemical tests, no symptoms of liver disease, and a compatible or diagnostic histological pattern — become symptomatic in 5 to 7 years in 40% of cases, and over 20 years more than 95% of them develop symptoms. Patients who are initially symptomatic, with symptoms both clinically and on laboratory tests, progress more rapidly to end-stage liver failure than those who are asymptomatic. Persistent jaundice that appears later in the disease is also related to a worse prognosis.
Progression to cirrhosis
The histological stage gives an estimate of how quickly cirrhosis will develop. From each Ludwig stage (the four-stage histological grading of PBC), the estimated time to cirrhosis is:
- stage 1 — 25 years
- stage 2 — 20 years
- stage 3 — 4 years
As fibrosis advances, cirrhosis develops with portal hypertension (raised pressure in the portal venous system) and its consequences, including variceal bleeding, ascites and hepatic encephalopathy.
Hepatocellular carcinoma
Cirrhosis is not the only serious complication. The risk of hepatocellular carcinoma, the primary cancer of liver cells, is 19-fold higher in patients with PBC than in the general population.
Prognosis
Treatment changes this course. With treatment, 10-year liver transplant-free survival is about 80%, compared with about 60% in untreated patients. Predictors of progression and of an inadequate response to treatment include higher alkaline phosphatase and bilirubin, lower albumin and platelet count, a greater degree of hepatic fibrosis, younger age at diagnosis, and male sex.