Factors Associated With Progression and Outcomes of Early Stage Primary Biliary Cholangitis

Abstract

BACKGROUND & AIMS:Patients usually receive a diagnosis of primary biliary cholangitis (PBC) at an early stage, based on biochemical analyses. We investigated the proportion of patients who progress to moderate or advanced PBC and factors associated with progression and patient survival. METHODS:We obtained data from 1615 patients (mean age, 55.4 y) with early stage PBC (based on their normal levels of albumin and bilirubin), collected at the time of initial evaluation or treatment, from the Global PBC Study Group database (comprising patients at 19 liver centers in North American and European countries). We collected data from health care evaluations on progression to moderate PBC (abnormal level of bilirubin or albumin) or advanced-stage PBC (abnormal level of both). The median follow-up time was 7.9 years. The composite end point was decompensation, hepatocellular carcinoma, liver transplantation, or death. RESULTS:Of the 1615 patients identified with early stage PBC, 904 developed moderate PBC and 201 developed advanced disease over the study period. The proportions of patients who transitioned to moderate PBC at 1, 3, and 5 years were 12.9%, 30.2%, and 45.8%. The a Authors share co-first authorship.

Primary biliary cholangitis management: controversies, perspectives and daily practice implications from an expert panel

“…39 Moreover, preliminary data from 20 patients showed a correlation between DR and the probability to respond to the first-line therapy (ie to moderate PBC. 41 The same variables except male sex were also significantly associated with the transition from moderately advanced to advanced disease. 41 It is worth noting that, even if the biochemical response to UDCA is the most important factor for risk stratification, inadequate responders may still experience an improvement in TFS.…”

“…41 The same variables except male sex were also significantly associated with the transition from moderately advanced to advanced disease. 41 It is worth noting that, even if the biochemical response to UDCA is the most important factor for risk stratification, inadequate responders may still experience an improvement in TFS. 10 The tools for risk stratification include:…”

“…Currently, patients are stratified in low‐ and high‐risk disease based on UDCA response, and the factors associated with the highest risk of complications are age at onset (the younger the patient, the higher the risk of progression), male gender (although evidence is not solid, males seem to have a higher risk of neoplastic transformation in case of advanced liver disease and when non‐responders to UDCA), stage at onset and serum ALP and bilirubin levels 1 . Recently, Gatselis et al identified male sex, baseline levels of bilirubin, albumin and ALP, aspartate to alanine aminotransferase ratio (AST/ALT), platelet count and treatment with UDCA as predictive of transition from early to moderate PBC 41 . The same variables except male sex were also significantly associated with the transition from moderately advanced to advanced disease 41 .…”

Review article: pathophysiology and management of primary biliary cholangitis

“…In broad terms, the ultimate treatment goal should be to normalise bilirubin and ALP levels, as attainment of bilirubin levels ≤0.6 x the upper limit of normal (ULN) or normal ALP is associated with the lowest risk for liver transplant or death 68 . Biochemical response to therapy also risk stratifies those patients at higher risk of developing complications, namely cirrhosis and liver failure 59 . Unfortunately, as many as 40% of patients do not have sufficient response to UDCA, which thus portends to inferior outcomes 69 .…”

“…Following initial bile duct injury, the cycle of cholestatic injury and cell death persists in PBC, eventually leading to destruction of intrahepatic biliary ducts with cholestasis and fibrosis 54 . Historically in the absence of therapy, of patients with early‐stage PBC, 46% will progress to a more severe stage within 5 years when untreated, with increased risks of decompensation, hepatocellular carcinoma (HCC), liver transplantation or death 59 …”