Optimal timing of hepatitis C treatment for patients on the liver transplant waiting list

Abstract

The availability of oral direct-acting antiviral (DAAs) has altered the hepatitis C virus (HCV) treatment paradigm for both pre- and post-liver transplant (LT) patients. There is a perceived trade-off between pre- versus post-LT treatment of HCV—treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT-eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre-LT treatment based on their MELD scores. We simulated a virtual trial comparing long-term outcomes of pre- versus post-LT HCV treatment with oral DAAs for patients having MELD scores between 10 and 40. We developed a Markov-based microsimulation model, SIM-LT (simulation of liver transplant candidates), which simulated the life course of patients on the transplant waiting list and after LT. SIM-LT integrated data from recent trials of oral DAAs (SOLAR 1 and 2), United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1-year and 5-year patient survival, and mortality. Model-predicted patient-survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD ≤ 27, but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre-LT varied between 23 and 27, and was lower for UNOS regions 3, 10 and 11, and higher for regions 1, 2, 4, 5, 8 and 9. Sensitivity analysis showed that the thresholds were stable. Conclusions Our findings suggest that the optimal MELD threshold below which decompensated cirrhotic patients should receive HCV treatment while awaiting LT is between 23–27, depending on the UNOS region.

Liver transplant listing for hepatitis C‐associated cirrhosis and hepatocellular carcinoma has fallen in the United Kingdom since the introduction of direct‐acting antiviral therapy

“…The potential adverse consequences of this may be more marked in the UK as waiting time for liver transplantation is longer than other countries. The MELD cut off has been reported as a point beyond which the probability of harm from DAA therapy is greater than the probability of benefit …”

The optimal timing of hepatitis C therapy in liver transplant‐eligible patients: Cost‐effectiveness analysis of new opportunities

“…Other studies have investigated the optimal timing of DAA treatment for patients listed for transplant, using a decision analytical model . The first was the study by Njei et al that considered only patients with decompensated cirrhosis without HCC.…”

“…This study also confirms that treatment prior to LT is the most cost‐effective for patients with a MELD>10. A third study from Chatwal et al evaluated the trade‐off between treating HCV patients with decompensated cirrhosis before or after LT considering only the change in life expectancy without including the cost and QALYs associated with the treatment strategies. Once again, the PRE‐LT treatment emerged as more effective for patients with a MELD score lower than 23.…”

Management of portal hypertension before and after liver transplantation

“…When suffering from HCV and receiving DAAs, MELD score decreases, leading to a longer wait-list time with potential negative impact on mortality. In a recent study by Chhatwal et al, MELD scores between 23 and 27 were identified as optimal time point (in the US setting) to better defer DAA treatment to the early post‐OLT period. Currently, there exists no specific medical treatment for NAFLD, thus lifestyle interventions and physical activity should be recommended. Mild strength training seems beneficial because this might counteract sarcopenia, which is associated with significantly worse outcomes both on the waiting list and after OLT …”