Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort

Abstract

Background: Many patients with primary biliary cirrhosis (PBC) are asymptomatic at the time of diagnosis. However, because most studies of asymptomatic PBC have been small and from tertiary centres, asymptomatic PBC remains poorly characterised.

Aims: To describe the features and progression of initially asymptomatic PBC patients.

Methods: Follow up by interview and note review of a large geographically and temporally defined cohort of patients with PBC, collected by multiple methods.

Results: Of a total of 770 patients, 469 (61%) were asymptomatic at diagnosis. These patients had biochemically and histologically less advanced disease than initially symptomatic patients. Median survival was similar in both groups (9.6 v 8.0 years, respectively) possibly due to excess of non-liver related deaths in asymptomatic patients (31% v 57% of deaths related to liver disease). Survival in initially asymptomatic patients was not affected by subsequent symptom development. By the end of follow up, 20% of initially asymptomatic patients had died of liver disease or required liver transplantation. The majority of initially asymptomatic patients developed symptoms of liver disease if they were followed up for long enough (Kaplan-Meier estimate of proportion developing symptoms: 50% after five years, 95% after 20 years). However, 45% of patients remained asymptomatic at the time of death.

Conclusions: Although asymptomatic PBC is less severe at diagnosis than symptomatic disease, it is not associated with a better prognosis, possibly due to an increase in non-hepatic deaths. The reasons for this are unclear but may reflect confounding by other risk factors or surveillance bias. These findings have important implications for future treatment strategies.

Figure 1

Kaplan-Meier estimates of patient survival from the time of diagnosis in initially asymptomatic and symptomatic patients.

Figure 2

Kaplan-Meier estimates of patient mortality due to liver disease from the time of diagnosis in initially asymptomatic and symptomatic patients.

Figure 3

Proportion of deaths (with 95% confidence interval) attributable to liver disease in initially asymptomatic patients at increasing time from diagnosis.

Figure 4

Kaplan-Meier estimates comparing patient survival in initially asymptomatic patients before and after symptom development.