Curing hepatitis C: A double-edged sword for liver transplant candidates?

The current treatment options for hepatitis C are highly efficacious and generally safe. Despite these impressive achievements accomplished in recent years, certain patient populations could in fact be harmed indirectly by these drugs, as the cure from the virus could prevent these patients from receiving a liver transplant despite the medical need of these patients to receive a new graft. Therefore, in cases of advanced liver disease, care must be taken in evaluation the patient’s circumstances to decide if antiviral treatment should be initiated prior to a transplant.

Chronic infections with the hepatitis C virus (HCV) have long been associated with low cure rates, advanced liver disease, and ultimately death. Fortunately, the development of direct-acting-antivirals (DAAs) has improved cure rates, defined as sustained viral response at 12-weeks post treatment completion (SVR12). Novel DAA regimens, including recently approved pangenotypic combinations as well as late-stage pipeline products, can achieve SVR12 rates >95% in the majority of patients and >90% in difficult to-treat-patients.

The apparent success in the treatment of hepatitis C, however, also has a surprising drawback for some patients. A result of chronic HCV infections, as well as other liver diseases, can be advanced liver cirrhosis and even decompensated liver cirrhosis. Using the Model for End-Stage Liver Disease (MELD) scoring system, patients with advanced liver cirrhosis might require a liver transplant for survival. Unfortunately, the number of patients placed on a waitlist for liver transplantations far exceeds the number of donor grafts available. Hence, climbing in the priority ranking, most notably by an increased MELD score, is an important step in receiving a liver transplant.

Although curing HCV using novel DAAs improves the patient’s composition, it consequently also lowers the patient’s MELD score without reducing the impact of the underlying cirrhosis. Hence, depending on the patient, being cured of HCV can be detrimental in some cases. Researchers presenting their work at the European Association for the Study of the Liver (EASL) conference this week in Amsterdam emphasized the useful criteria in deciding which patients to treat with DAAs and under which circumstances treatment should be initiated after transplantation.

In general, patients with compensated liver cirrhosis, a MELD score below 20, and Child-Pugh score A (CP-A) should always receive DAA treatment prior to liver transplant, while individuals with decompensated liver cirrhosis, a MELD score >30, and CP-C would in general benefit from administration of DAAs following a successful liver transplantation. For all patients falling between these two groups, careful examination must be performed for age, previous DAA exposure, severity of portal hypertension, as well as the precise MELD score and how this score relates to the positioning in the national/local liver transplant waitlist.  If these factors are not considered, patients with a MELD score between 20 and 30 might be cured of HCV, resulting in a MELD score <20 and thereby significantly extend their waiting time for a graft, significantly increasing the mortality rates of those individuals, a circumstance described by clinicians as MELD purgatory.