Patients with hepatitis C virus (HCV) who achieve a sustained virologic response have better outcomes after liver transplant and do not require post-transplant fibrosis monitoring.

“Prior to direct-acting antiviral (DAA) agents that cure HCV, many patients had poor outcomes after liver transplant,” Kymberly D. Watt, MD, explains. “Hepatitis C inevitably recurred and caused fibrosis and cirrhosis in the transplanted allograft.”

As a result, Dr. Watt says most transplant centers utilized protocol biopsies to monitor the degree of scarring progression.

However, there was limited research examining the development of fibrosis, progression, and/or regression among liver transplant recipients who had been treated for HCV, she continues.

For a study published in Clinical Transplantation, Dr. Watt and colleagues retrospectively assessed 226 consecutive liver transplant recipients with HCV from 2007 to 2018. They categorized patients into pre- and post-DAA cohorts to reflect the introduction of DAAs. “When we did this study, there were still many patients that had already had an HCV-related liver transplant and had some degree of fibrosis in the allograft,” Dr. Watt notes. “It was not clear if this would regress, stay stable, or progress once the virus was eradicated with these new antiviral agents.”

The researchers aimed to determine whether post-transplant monitoring for fibrosis was necessary among patients who achieved a sustained virologic response (SVR) with DAA agents before or after transplant.

Pre-Transplant SVR Reduces Graft Loss & Mortality

Patients who received a liver transplant after the introduction of DAAs had significant improvements in HCV treatment rates and earlier achievement of SVR compared with patients who received a liver transplant prior to the introduction of DAAs, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (P<0.001). Before attaining SVR, patients who underwent transplant before the advent of DAAs had worsening fibrosis stage yearly (+0.21; P<0.001), while those receiving a transplant after the introduction of DAA therapy had minimal changes to annual biopsy.

Following SVR, most patients received non-invasive follow-up and showed stable or improved fibrosis stage over time.

“It is not a surprise that the percentage achieving SVR is higher, as these drugs are just that much better,” Dr. Watt says. “The majority of patients come into transplant now with SVR. What is important to stress are the improvements in transplant-related outcomes, as well as a reduction in graft loss and less HCV-related mortality in the post-transplant setting.”

Although it has become unusual for a patient to need HCV treatment after a liver transplant, Dr. Watt notes that clinicians can anticipate a high rate of SVR.

Assessing Fibrosis After Attainment of SVR

According to Dr. Watt, the study showed that there is no need for continued monitoring of fibrosis in patients who had fibrosis from a previous case of recurrent HCV. “The relevance of the study for clinicians lies in knowing how to monitor those patients who already had fibrosis from HCV before DAA therapy could eradicate the virus.”

The new generation of hepatologists who have completed their training since the advent of DAA therapy “have never had experience with the morbidity and mortality of recurrent HCV in transplant patients,” Dr. Watt notes.

“An entire generation of hepatologists will never experience the carnage of recurrent HCV,” she says. “Previously, HCV universally recurred in the transplanted allograft and caused significant fibrosis, cirrhosis, and graft failure on a routine basis. It was a leading cause of allograft failure, liver re-transplantation, and death after transplant. Following this fibrosis progression and allograft injury was a complicated process. With the advent of DAA agents and the successful eradication of HCV, we have experienced a transformation in transplant outcomes for HCV-related cirrhosis.”

Key Takeaways

• Achieving sustained virologic response (SVR) prior to liver transplant improves transplant-related outcomes and reduces graft loss and HCV-related mortality
• For patients with fibrosis due to recurrent HCV who achieve SVR, there is no need for continued fibrosis monitoring after the transplant