COMMENTARY

A Future Without Hepatitis C?

The Liver Meeting 2014: American Association for the Study of Liver Diseases (AASLD)

William F. Balistreri, MD

Disclosures

December 16, 2014

In This Article

HCV Recurrence After Liver Transplantation

In patients who are viremic at the time of liver transplantation, HCV recurrence is universal and is associated with reduced graft and patient survival. In fact, recurrence of HCV infection is the most common cause of graft loss and mortality in HCV-infected liver transplant recipients. IFN-based antiviral regimens, including those utilizing protease inhibitors, are poorly tolerated after transplantation and achieve lower SVR rates than in nontransplant patients. Presentations at this year's meeting offered insight into new prevention and treatment options in this setting.

ABT-450/r/Ombitasvir and Dasabuvir Plus Ribavirin

In a study published simultaneously in the New England Journal of Medicine, Mantry and colleagues[24,25] examined the safety and efficacy of an all-oral 24-week 3D regimen of ABT-450/r/OMB and DAS plus RBV in 34 noncirrhotic liver transplant recipients. Recipients with recurrent HCV genotype 1 infection achieved high SVR rates (97%) with the IFN-free 3D/RBV regimen; the agents were generally well tolerated and drug-drug interactions were manageable.

Simeprevir/Sofosbuvir to Treat Genotype 1 in Liver Transplant Setting

Aqel and colleagues[26] reported the cumulative experience of three US liver transplant centers in treating 127 patients with the SMV/SOF combination. All patients were HCV RNA negative at week 12 and no treatment relapses were seen. The drugs were well tolerated by this difficult-to-treat population of patients, most of whom had cirrhosis, and who were ineligible, previously intolerant, or nonresponsive to IFN-based therapy. No episodes of hepatic decompensation were documented.

Sofosbuvir/Simeprevir to Treat Genotype 1 After Liver Transplantation

Pungpapong and colleagues[27] reported the virologic response, safety, and tolerability of SOF/SMV with or without RBV for 12 weeks in treating liver transplant recipients with HCV genotype 1. This all-oral antiviral regimen was well tolerated and resulted in excellent on-treatment virologic responses.

Sofosbuvir/Daclatasvir for Recurrent HCV After Liver Transplantation

SOF and DCV have a high barrier to resistance, lack interactions with immunosuppressive agents, and have a favorable safety profile. In a single-arm, open-label, IFN-free pilot study, 55 patients with recurrent HCV infection (any genotype) after liver transplantation received up to 24 weeks of SOF (400 mg) and DCV (60 mg) daily.[28] By weeks 2, 4, and 8 of treatment, virologic response rates were 17%, 50%, and 85%, respectively. There were no episodes of acute or chronic rejection. SOF/DCV therapy was well tolerated.

Ledipasvir/Sofosbuvir With Ribavirin in Posttransplant Recurrence

Reddy and colleagues[29] evaluated the safety and efficacy of LDV/SOF with RBV in 223 patients with recurrent HCV (genotypes 1 and 4) at a median of 4.4 years after transplant. Administration of LDV/SOF/RBV was well tolerated, with high efficacy. Preliminary data demonstrated no apparent difference between 12 and 24 weeks of treatment. The most common adverse events were fatigue, anemia, headache, and nausea.

Fibrosing Cholestatic Hepatitis

Fibrosing cholestatic hepatitis is a rare but severe form of HCV-recurrence following liver transplantation. Leroy and colleagues[30] assessed the efficacy and tolerance of SOF and DCV-based regimens in this setting. The rates of liver enzyme (alanine aminotransferase and gamma glutamyl transferase) normalization at week 12 were 76% and 52%, respectively. Median serum bilirubin levels declined from 6.0 mg/dL to 3.6 mg/dL at week 1 and to 2.6 mg/dL at week 2. At week 12, 90% of patients had bilirubin levels below 2 mg/dL. Complete clinical response (no ascites and bilirubin < 2 mg/dL) was observed in 71% of patients at week 12.

Prevention of HCV Recurrence

Terrault and colleagues[31] evaluated the safety and efficacy of Biotest-HCIG (Biotest; Boca Raton, Florida), a human hepatitis C immune globulin to prevent HCV recurrence by neutralizing remaining HCV reservoirs. In this phase 3, open-label, randomized study, 84 wait-listed patients with chronic HCV infection (all genotypes) treated with any antiviral therapy and who achieved HCV RNA < 100 IU/mL before liver transplant were eligible. HCV recurrence rates in patients receiving antiviral therapy pre–liver transplant were lower in Biotest-HCIG-treated patients compared with controls (8% vs 20%). All patients who were viremic at liver transplant and received Biotest-HCIG had undetectable HCV RNA. These preliminary results suggest that Biotest-HCIG may be beneficial as an adjuvant therapy for HCV patients on antiviral therapy undergoing liver transplant.

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