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Boston 2016: HCV Treatment
How Data From the 2016 Boston Hepatology Meeting Will Influence Future HCV Patient Management

Released: January 31, 2017

Expiration: January 30, 2018

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I am really enjoying treating patients with HCV infection in this era of highly effective direct-acting antivirals (DAAs). Think about it: Our patients present with life-threatening, chronic infections, and we cure more than 95% of them with few adverse events. Other than insurance challenges, what’s not to love?

Despite the relatively easy road to cure with modern therapy in most of my HCV-infected patients, I can think of 2 recent patients who presented challenges: a patient with relapse and resistance associated substitutions (RASs) after treatment with a DAA and a patient with genotype 3 HCV infection and severely reduced renal function.

Will these patients have the opportunity to achieve HCV cure with simple, safe, and effective DAA therapy? After the 2016 hepatology meeting in Boston, the answer is yes!

Relapse and Resistance
The first patient was a 59-year-old black man with genotype 1a HCV infection and stage 3 fibrosis. We treated him with 12 weeks of ledipasvir/sofosbuvir, and it was going very well until he had posttreatment relapse. He was one of the 5% of patients who do not achieve HCV cure. Testing for RASs revealed NS3 Q80K and NS5A Y93H.

For this patient, the POLARIS-1 study offers a guiding light. In this study, the 3-drug, fixed-dose combination of sofosbuvir (SOF), velpatasvir (VEL), and the pangenotypic HCV NS3 protease inhibitor voxilaprevir (VOX) taken once daily for 12 weeks led to HCV cure in 96% of 263 persons who, like my patient, had failed to respond to NS5A-containing DAA regimens.

In fact, in the POLARIS-4 study, in DAA-experienced patients who had not received an NS5A inhibitor, 12 weeks of this 3-drug combination that includes VOX was also more effective than the current 2-drug combination of SOF/VEL without VOX (SVR12: 97% vs 90%, respectively).

Furthermore, RASs had no effect on SVR12 for SOF/VEL/VOX in either of these studies.

In the United States, the expectation is that this triple regimen will be available in mid-2017 for the treatment of persons infected with genotypes 1-6 HCV in whom DAA treatment failed to achieve HCV cure. Based on these results, I will recommend that my patient wait for this agent to become available.

Genotype 3 and Chronic Kidney Disease (CKD)
My second patient was a 44-year-old woman, born in Pakistan, with genotype 3 HCV infection and stage 4 HCV-related CKD (with an estimated glomerular filtration rate eGFR of approximately 25 mL/min). Her hepatitis C needed to be cured, but the recommended regimen for treatment of persons with genotype 3 infection and renal disease is peginterferon and weight-based ribavirin—not an ideal regimen. The other option is the off-label use of SOF/VEL, which is not recommended in the setting of CKD with eGFR < 30 mL/min owing to the accumulation of GS-331007, the inactive metabolite of SOF.

For this patient, the EXPEDITION-4 study appears to offer a peginterferon- and ribavirin-free path to HCV cure. In this study, the 2-drug combination of the NS3 protease inhibitor glecaprevir (GLE) and next-generation NS5A inhibitor pibrentasvir (PIB), taken as 3 tablets once daily, led to HCV cure in 98% of 104 patients with stage 4/5 CKD, most of whom were on dialysis (82%). This is a pangenotypic HCV regimen that is expected to be the treatment of choice for persons with CKD and HCV genotype 2/3 infection in mid-2017, which may finally banish peginterferon as a recommended therapy for hepatitis C.

For my patient, the question remains: What should I recommend for her genotype 3 HCV infection and CKD? For now, my plan is to hold off on HCV treatment until GLE/PIB is approved. This will also give her time to consider kidney transplantation options down the road.

Furthermore, in persons without cirrhosis, the ENDURANCE-1 study showed glecaprevir/pibrentasvir (GLE/PIB) to be highly effective (SVR12: 99%) when used for only 8 weeks in patients with HCV genotype 1.

My expectation is that, following the approvals of SOF/VEL/VOX and GLE/PIB, ribavirin will be used for only a handful of patients. Ribavirin has been a gritty solider in the fight against hepatitis C, but like interferon, I will not miss prescribing this drug.

Future Challenges
The 2016 hepatology meeting in Boston offered future solutions to some of my most vexing patient challenges—solutions that promise to bring more joy to my clinic. Easy Street, right? Well, the meeting did leave us with some new challenges.

An observational, postmarketing study found that HBV reactivation sometimes occurs during HCV DAA treatment, and a prospective study in cirrhotic patients reminds us that the risk of hepatocellular carcinoma is ongoing, even following cure.

For these issues, the meeting provided more data but little consensus, so their clinical management will remain complex for now.

I am interested to hear how new data from Boston are affecting your management of hepatitis C. Feel free to join in the conversation below.

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