COMMENTARY

HCV Treatment: What Can I Do Now? What's Coming Next?

Rowen K. Zetterman, MD

Disclosures

August 24, 2015

In This Article

Options for Difficult-to-Treat Patients

The HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C website[16] provides recommendations for the treatment of patients with decompensated HCV cirrhosis (Child-Turcotte-Pugh class B or C), suggesting that these patients are best treated by "highly experienced HCV practitioners." Please refer to these guidelines for their full therapeutic recommendations.

HCV is associated with the development of chronic renal failure from glomerular diseases, such as membranoproliferative glomerulonephritis associated with type II cryoglobulinemia.[30] The guidelines note that safety and efficacy data are not available for patients with creatinine clearance less than 30 mL/min.

Patients with HCV and HIV-1 coinfection are also more likely to develop cirrhosis than are HCV monoinfected patients,[31] and past HCV treatments have not been effective in this group.

Latest Results

Cirrhosis. For patients with compensated cirrhosis, studies of grazoprevir/elbasvir with or without ribavirin[32] and sofosbuvir plus pegylated interferon/ribavirin or ribavirin only (BOSON)[33] have been reported.

With grazoprevir/elbasvir,[32] neither the addition of ribavirin nor providing longer treatment at 18 weeks (compared with 12 weeks) resulted in significant improvement of SVR in previously untreated patients with cirrhosis. This was demonstrated by an SVR with ribavirin of 90% at 12 weeks vs 97% at 18 weeks, and an SVR of 97% at 12 weeks vs 94% at 18 weeks for treatment without ribavirin. The SVR for treatment nonresponders with or without cirrhosis was similar at 12 weeks (94% with ribavirin and 91% without) and 18 weeks (100% with ribavirin and 97% without). The SVR rates at 12 weeks for previously treated patients with cirrhosis was 94% for genotype 1a and 100% for genotype 1b, with no significant improvement in viral clearance with added ribavirin.

The BOSON study[33]treated genotype 2-infected patients with cirrhosis and genotype 3-infected patients with or without cirrhosis, using sofosbuvir plus pegylated interferon/ribavirin for 12 weeks, or sofosbuvir plus ribavirin for 16 or 24 weeks. The SVR in genotype 2-infected patients with cirrhosis was high in all treatment groups. For genotype 3-infected patients, the combination of sofosbuvir plus ribavirin for 24 weeks was superior to treatment for 16 weeks. For interferon-eligible patients with genotype 3 infection, sofosbuvir plus pegylated interferon/ribavirin had the highest response rates at 12 weeks of treatment.

HCV/HIV coinfection. Patients with HCV and HIV-1 coinfection are more likely to develop cirrhosis than HCV-monoinfected patients.[31] If HCV clearance can be achieved in patients with HIV-1 infection, complications of end-stage liver disease will be reduced.[34]

The requirement of interferon-based treatment in the past has limited therapy of coinfected patients. Grazoprevir/elbasvir with or without ribavirin for either 8 or 12 weeks was compared in HIV-infected patients with genotype 1 HCV coinfection (72% with genotype 1a) and HCV-monoinfected patients.[35] The SVR rates for patients not receiving ribavirin were 98% in monoinfected and 87% in coinfected patients, with SVR better at 12 weeks of therapy than 8 weeks. For patients receiving additional ribavirin, SVR rates were 93% in monoinfected and 97% in coinfected patients. On the basis of confidence intervals, no difference was noted in the SVR after HCV treatment regardless of whether ribavirin was added or not.

In open-label drug trials of patients with HCV/HIV coinfection, ombitasvir, paritaprevir/ritonavir, and dasabuvir plus ribavirin resulted in a 12-week SVR of 94%,[36] and therapy with ledipasvir plus sofosbuvir produced an SVR of 98%.[37]

These results indicate that HCV can be successfully treated with direct-acting antiviral drugs in patients with HCV/HIV coinfection.

Renal failure. For patients with renal failure, an early report of an open-label trial of 12 weeks of ombitasvir, paritaprevir/ritonavir, and dasabuvir with (genotype 1a) or without (genotype 1b) low-dose ribavirin (200 mg daily) in previously untreated patients without cirrhosis was recently presented.[38] Two thirds of patients in the study had a glomerular filtration rate of less than 15 mL/min, and 65% of patients were on hemodialysis. Ten of 13 patients developed an SVR at 12 weeks from treatment. Additional studies are needed in patients with renal failure to determine best treatment.

Remaining Questions

Newer direct-acting antiviral drugs are changing the treatment of patients with chronic HCV.

Yet, additional studies of these new drugs are needed to assess the treatment responses of all HCV genotypes; clarify the necessary duration of therapy in treatment-naive patients; and define the best treatment regimens for patients with compensated and decompensated cirrhosis, those with comorbid disorders such as renal disease, and those awaiting liver transplantation.

Underlying all these questions, of course, is the larger one of whether we should be treating asymptomatic patients with HCV infection who lack evidence of complications, or only those with progressive or advanced HCV disease.

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