Editorial: liver transplantation for primary biliary cholangitis–the need for timely and more effective treatments

The approach to managing primary biliary cholangitis (PBC) has certainly changed since Dame Sheila Sherlock described her famous case series in 1959. In the first two decades after the first liver transplantation (LT) in 1963, primary biliary “cirrhosis,” as the disease used to be called before the long‐awaited change in nomenclature in 2015, was the main indication for LT in Europe. The introduction of anti‐mitochondrial antibody testing has allowed an earlier diagnosis and the registration of ursodeoxycholic acid (UDCA) has offered a tool to halt the progression of the disease. Nonetheless, from 20% to 50% of all PBC individuals are still “nonresponders” to current treatments, and consequently prone to progress to end‐stage liver disease (ESLD) and potential need for LT. In a recent issue of AP&T, Harms et al address an open question —whether and how numbers of LT for PBC in Europe have been changing over the last three decades (1986‐2015). They also investigate a well‐characterised cohort including all Dutch subjects transplanted for PBC, to see whether features of patients have changed and, if so, in which trajectory. Over three decades, there was a relative reduction of PBC transplantations when compared to other indications, more prominent in the first decade, when alcohol‐related liver diseases and viral hepatitis revealed a vast increase. It is notable that the absolute annual number of transplants for PBC has been stable from 1995 to 2015, with an average of 200 PBC patients transplanted in Europe every year. It turns out that end‐stage liver disease secondary to PBC remains a major indication for LT, and the core of patients with aggressive disease is still there. It might be worth highlighting that autoimmune hepatitis (AIH)/PBC variant cases, a category with faster progression to ESLD, are under‐reported in the ELTR and these may actually contribute to the increase in number of LT patients for PBC. Moreover, as mentioned by Harms et al, numbers of LT for PBC might be higher still, considering that a significant proportion of PBC listed patients die before being transplanted. Interestingly, the relative proportion of males transplanted for PBC is increasing. In addition to the explanations provided by authors (an epidemiological change, a reduced rate of response in males), we suggest that males might experience a diagnostic delay, which in turn may impact on treatment response and disease progression. Lastly, the analyses on the Dutch cohort reveal a far younger median age at diagnosis compared with international studies on PBC, confirming that younger age at diagnosis in PBC portends a worse prognosis. Overall these data highlight the urgent need to improve the care for those PBC patients that progress to liver failure due to lack of effective therapies. The registration of obeticholic acid and the many new molecules currently in the pipeline do offer new hope for patients, but at the same time, we should improve stratification of PBC patients, allowing clinicians to offer a timely treatment to individuals prone to experience worse outcomes. “To offer the right drug, to the right patient, at the right time” is indeed the leitmotif of modern medicine.