William F. Balistreri, MD

Disclosures

December 27, 2013

In This Article

A Rapid Pace of Progress in Hepatology

The clinical practice of hepatology promises to change dramatically in the next few years. This optimistic view is based on the excitement generated by research presented at The Liver Meeting® -- the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

Investigators highlighted the pace of progress in understanding common forms of liver disease, such as viral hepatitis, cholestasis, and fatty liver disease. Of specific interest, presentations focused on the availability of novel diagnostic and therapeutic options, which present a strong, cogent argument for an enhanced screening methodology to ensure optimal outcomes for our patients.

Here is my "top 10" list of the concepts emerging from this year's meeting.

A Future Without Hepatitis C

The successful development of targeted therapies for patients with chronic hepatitis C virus (HCV) was clearly evident. Several companies are jockeying to be the first to offer an all-oral, interferon (IFN)-free strategy. On the near horizon is the promise that a cocktail of agents, constructed on the basis of synergistic mechanisms of action, will be available for clinicians to wisely, effectively, and safely treat patients with HCV infection. A major advance, in my opinion, is the validation of regimens that are devoid of IFN and, in some cases, ribavirin.

Chayama and colleagues[1] documented the safety and efficacy of an IFN/ribavirin-free, all-oral therapy with daclatasvir (60 mg once daily) and asunaprevir (100 mg twice daily) in IFN-ineligible, -naive, or -intolerant patients and in those who did not respond to standard treatment for HCV genotype 1b.

Daclatasvir is a novel NS5A replication complex inhibitor with pangenotypic antiviral activity. Asunaprevir is a potent NS3 protease inhibitor with antiviral activity against genotypes 1, 4, 5, and 6. This regimen was associated with high (87%) sustained virologic response (SVR) rates after 12 weeks in both groups of patients. Treatment with this dual therapy was well tolerated.

Another all-oral triple combination -- daclatasvir, asunaprevir, and BMS-791325 (a nonnucleoside NS5B inhibitor) -- achieved SVR rates > 90% in pilot cohorts of noncirrhotic patients with HCV genotype 1 infection. Everson and colleagues[2] evaluated this regimen in larger cohorts that included cirrhotic patients. Patients received a twice-daily regimen of daclatasvir (30 mg), asunaprevir (200 mg), and BMS-791325 (either 75 mg or 150 mg) for 12 weeks. This investigational combination, which likewise avoids the use of both IFN and ribavirin, allowed a high percentage (92%) of patients infected with HCV to achieve SVR, including 87% of cirrhotic patients. The most frequent adverse effects in both groups were headache, diarrhea, fatigue, and nausea.

Lawitz and colleagues[3] reported successful results with another strategy. They administered the investigational combination of ABT-450, an HCV NS3/4A protease inhibitor (150 mg, dosed with ritonavir 100 mg), with ABT-267, an NS5A inhibitor (25 mg). Both compounds have shown potent antiviral activity in vitro against HCV genotypes 1-4 and 6. This combination, given once daily for 12 weeks, reduced viral loads to undetectable levels 12 weeks after the end of treatment in 95% of treatment-naive patients and in 90% of patients who had been previously treated but did not respond. The regimen was generally well tolerated. There were no serious adverse events related to the study drugs, and no patients stopped treatment because of adverse events.

Other reported regimens included a once-daily combination of simeprevir plus sofosbuvir (2 novel agents that were recently approved by the US Food and Drug Administration), with or without ribavirin, in patients with cirrhosis and noncirrhotic HCV genotype 1 treatment-naive and previous null responders.[4] One study[5] reported the effect of sofosbuvir and ribavirin for the treatment of recurrent HCV infection after liver transplantation, and another study[6] reported that sofosbuvir and ribavirin can be administered before transplant to prevent recurrence of HCV infection after liver transplantation.

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