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Ribavirin boosts HCV genotype 3 eradication in compensated cirrhotic patients

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Ribavirin helps treat resistant genotype 3 variants

The results from Dr. Drysdale’s analysis confirm what had previously been proposed by other investigators that, in a subgroup of patients with cirrhosis and infected with hepatitis C virus (HCV) genotype 3, adding ribavirin to a regimen of direct-acting antiviral drugs can increase efficacy. But the new study included no data to address the prevalence of HCV genetic variants with resistance mutations that necessitate adding ribavirin. We have known that, in patients with cirrhosis and infected with resistant genotype 3 HCV, adding ribavirin is necessary. In many locations resistance testing is not possible; in those circumstances, adding ribavirin to the treatment should be routinely done.

Dr. Thomas Berg, professor of medicine, University Hospital, Leizig, Germany Mitchel L. Zoler/MDedge News

Dr. Thomas Berg

It’s also been well known that the more advanced a patient’s liver disease, the harder it is to eradicate HCV infection. In general, patients with decompensated liver disease have sustained virologic response rates that are about 10% below the rate in patients without cirrhosis, and Dr. Drysdale reported a similar finding. This fact compels us to diagnose and treat HCV infections earlier. The current focus of the field is on screening for HCV infection among younger adults with risk factors for infection. Unfortunately, many people with an HCV infection are not in regular contact with their local health system, and in many parts of the industrialized world there is only weak practical support for comprehensive screening of at-risk people. Screening programs and recommendations exist, but today these are often ignored and higher-risk young adults frequently do not undergo HCV screening.

Thomas Berg, MD, is professor and head of hepatology at University Hospital in Leipzig, Germany. He has received personal fees and research support from several companies. He made these comments in an interview.



– In patients with compensated cirrhosis infected with genotype 3 hepatitis C virus, adding ribavirin to a usual antiviral regimen of sofosbuvir and velpatasvir significantly boosted the rate of sustained virologic response in a review of more than 14,000 English residents entered in a national registry starting in 2017.

Dr. Kate Drysdale, Queen Mary University of London Mitchel L. Zoler/MDedge News

Dr. Kate Drysdale

With ribavirin added to a sofosbuvir plus velpatasvir regimen for 12 weeks of treatment, the three-drug combination produced a 98% rate of sustained virologic response after 12 weeks (SVR12) in 196 treated patients, Kate Drysdale, MBBCh, said at the meeting sponsored by the European Association for the Study of the Liver. In contrast, 218 compensated cirrhosis patients who received a 12-week regimen of sofosbuvir plus velpatasvir (Epclusa) but without ribavirin had an SVR12 rate of just under 92%, a statistically significant difference, compared with the rate among patients who also received ribavirin, said Dr. Drysdale, a gastroenterologist at Bart’s Health and Queen Mary University of London. The SVR12 rate among 167 compensated cirrhotic patients treated for 12 weeks with the combination of glecaprevir plus pibrentasvir (Mavyret) was 96%, and not statistically different from the patients who received three drugs including ribavirin. The sofosbuvir, velpatasvir, ribavirin combination also outperformed the combination of sofosbuvir plus daclatasvir (Daklinza) and ribavirin, which produced an SVR12 of 92% in 868 patients. The SVR12 rate is the percentage of patients with undetectable hepatitis C virus (HCV) 12 or more weeks after the end of treatment.

Dr. Drysdale cautioned that the data have not yet been put through a multivariate analysis, but the results so far provide “a strong indication that ribavirin may not be as insignificant” as many have recently presumed. “Ribavirin has been set aside because it was thought not to add to the SVR12, but if patients get only one go at treatment, we must be sure their first treatment is the best one,” Dr. Drysdale said in an interview. If ribavirin can be shown to make a significant contribution to treatment efficacy “then we should think more widely about using it when patients tolerate it.”

The analysis included too few patients with either current decompensated cirrhosis or a history of decompensated cirrhosis to make any statistically meaningful comparisons of the treatment subgroups among these patients. And among patients with genotype 3 HCV infection and without cirrhosis, none of the treatments used in practice showed any statistically significant differences in the SVR12 rates they produced. Among patients without cirrhosis the most commonly used regimens by far were an 8-week course of glecaprevir plus pibrentasvir in 731 patients or a 12-week course of sofosbuvir plus velpatasvir in 1,184 patients. Both regimens had SVR12 rates in noncirrhotic patients of 97%, regardless of whether patients had no, mild, or moderate liver fibrosis.

The study used data collected in an English national registry of HCV-infected patients treated with direct-acting antiviral drugs starting in 2017. Dr. Drysdale and her associates narrowed down the total database of more than 37,000 English adults who received some HCV therapy during the period to 14,603 who received a complete, valid regimen and had follow-up SVR12 information available. The overall SVR12 rate among all these patients was 95.59%, and among the patients infected by genotype 3 virus the SVR12 rate was 95.03%. Dr. Drysdale’s analysis focused primarily on the roughly one-third of patients in the study group infected with genotype 3 HCV, the genotype that historically has presented unique treatment challenges (Drugs. 2017 Feb;77[2]:131-44).

Another finding Dr. Drysdale reported was that as liver disease severity worsened from no fibrosis to mild or moderate fibrosis, and then to compensated cirrhosis or decompensation, the SVR12 rate steadily diminished. Among genotype 3 patients, the SVR12 rate fell from about 97% among patients without any fibrosis to about 87% among those with decompensated cirrhosis. Although this observation had been made before, this finding in such a large number of treated patients adds significant new evidence to support this pattern. It also adds further support to the idea of screening for HCV infection among higher-risk, asymptomatic people to optimize their prospects for virus eradication with treatment.

“If patients get much better treatment outcomes before they become cirrhotic then we should try to find these HCV-infected people before they develop symptoms,” Dr. Drysdale said.

Dr. Drysdale reported no disclosures.

SOURCE: Drysdale K et al. J Hepatol. 2019 April;70(1):e131.

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