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The Liver Meeting 2016: Beyond HCV

In HCV, with the pangenotypic regimens, there are very few patients who are not going to have sustained virologic responses . We must now consider getting everyone tested and then everyone treated, as mentioned by Susanna Naggie, MD.

But as we work through those remaining holdouts, we are quickly moving into the post-hepatitis C era and I think that is already reflected in practice today. The number of patients coming to transplant with HCV seems to be diminishing. Instead, we are seeing an increase in patients with non-alcoholic fatty liver and a renewed focus on hepatitis B. It’s a dramatic change in a short period of time.

In my mind NAFLD is a bit like cardiovascular disease used to be in the U.S. A lot of the improvement in outcomes in cardiovascular disease were related to addressing the precipitants like hyperlipidemia and systemic hypertension and having good cholesterol medications. A big part of the effort in NAFLD needs to be with dealing with the precipitants before end-stage liver disease develops.

As regards pharmacological options for f for NASH we saw a variety of interesting presentations at the meeting indicating efficacy.

Arun J. Sanyal, MD, FAASLD, presented data on cenicriviroc (CVC, Tobira/Allergan) from the phase 2b CENTAUR study showing that although the primary endpoints were not met, the CVC-treated group had improvement in fibrosis by at least 1 stage and did not experience worsening of steatohepatitis compared with placebo (P = .023). More patients treated with CVC showed improvement in fibrosis by two stages (n = 8) compared with placebo-treated patients (n = 3). More patients treated with placebo progressed to cirrhosis compared with CVC-treated patients (2 vs. 5). In addition, IL-6, hsCRP and fibrinogen levels were decreased significantly in CVC-treated patients compared with placebo.

In the BMS-986036 (Bristol-Myers Squibb) phase 2 study, researchers showed improvement in other factors – triglycerides, LDL and HDL and an increase in serum adiponectin – and a good safety profile so the researchers suggest it addresses metabolic derangements and may have an anti-fibrotic effect.

In another phase 2 study, selonsertib (GS-4997, Gilead Sciences), an apoptosis signal-regulating kinase inhibitor (ASK1), showed a dose-dependent effect on fibrosis and steatosis endpoints. Fibrosis improvement was seen in 43% of patients receiving selonsertib 18 mg, 30% of patients receiving 6 mg and 20% of patients receiving simtuzumab alone, Rohit Loomba, MD, said. Improvement without NASH worsening was seen in 37% of the 18 mg group, 30% of the 6 mg group and 20% of the simtuzumab group. Progression of cirrhosis was seen in 3% (n = 1) of the 18 mg group, 7% (n = 2) in the 6 mg group and 20% (n = 2) in the simtuzumab group.

In reality, treating NAFLD and NASH is going to look different than treating HCV with a need for longterm rather than finite therapy The pendulum is also going to swing back to hepatitis B because we need a better approach to its management.

There are a lot of small biotechs in the hunt along with the now-approved tenofovir alafenamide (Vemlidy, Gilead Sciences).

At this meeting, one Late Breaker looked at two nucleic acid polymers — REP-2165 and REP-2139 (Replicor, Inc.) — used individually in triple combination with tenofovir disoproxil fumarate and pegylated interferon. The presenter showed efficacy and tolerability in patients with hepatitis B e antigen-negative hepatitis B virus infection.

Curative HBV treatment will likely be a combination regimen. It willinclude an oral antiviral agent with an immune modulator and possible something else in addition.

Despite these challenges we are witnessing remarkable advances in the management of chronic liver disease best exemplified by HCV therapy.

• References:
• Charles ED. Abstract 33. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.
• Loomba R. Abstract LB-3. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.
• Ohki T. Abstract 1156. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.

• For more information:
• Paul Martin, MD, can be reached at University of Miami Hospital, 1400 NW 12th Ave., Miami, FL 33136.

Disclosure: Martin reports financial relationships with AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck.