Advancing Our Understanding of HCV and NASH Treatment: New Data From EASL 2018

Zobair Younossi Headshot
Zobair M. Younossi, MD, MPH, FACP, FACG, AGAF, FAASLD

Professor and Chairman
Department of Medicine
Inova Fairfax Medical Campus
Falls Church, Virginia


Zobair M. Younossi, MD, MPH, FACP, FACG, AGAF, FAASLD, has disclosed that he has received consulting fees or funds for research support from Allergan, Bristol-Myers Squibb, Gilead Sciences, Intercept, Novartis, NovoNordisk, and Shinogi.


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Released: June 4, 2018

The 2018 International Liver Congress (ILC) in Paris, France, was an exciting meeting where many important new data were discussed. Here, I focus on some of the key research presentations affecting our understanding and treatment of patients with HCV infection or nonalcoholic steatohepatitis (NASH)

Patient-Reported Outcomes (PROs) in HCV
Although HCV infection continues to be an important cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide, highly effective and safe all-oral, interferon-free regimens offer almost universal sustained virologic response (SVR) after 8-12 weeks of treatment. At the ILC 2018 meeting, additional data were presented about the efficacy of these regimens in real-world practices as well as in special populations such as those with less common HCV genotypes or cirrhosis and patients on opioid substitution therapy.

Substantial evidence shows that patients with HCV infection suffer impairment of their PROs (eg, quality of life)—an impairment worsened in those with cirrhosis. Although SVR can improve PROs, the sustainability of these improvements has not been shown. During ILC 2018, long-term data from a registry of 786 patients with cirrhosis and HCV infection clearly demonstrated that durable PRO improvements, assessed with CLDQ-HCV, SF-36, and WPAI-HCV, persisted 96 weeks after SVR with interferon-free therapy.

These data provide evidence for the comprehensive benefits of achieving SVR, confirming that patients with HCV can experience not only better clinical outcomes (eg, lower chances of developing cirrhosis and liver-related mortality) but also better and sustained improvement of their PROs such as health-related quality of life. From a patient’s perspective, improvement in these endpoints is the most important outcome.

Emerging Treatments for NASH
Overall, the 2018 meeting reflected a shift in liver research from HCV to NASH, which is rapidly becoming the most important and common cause of liver disease worldwide. In the United States and other Western countries, NASH is already a prominent driver of cirrhosis, HCC, and liver transplantation, with negative impact on economics and PROs. Despite this increasing burden, and unlike the HCV treatment landscape, a lack of effective therapies for NASH exists.

It is notable, then, that results from a number of clinical trials of new agents for the treatment of NASH were presented at ILC 2018. Final analysis of the phase IIb CENTAUR study confirmed the antifibrotic activity of CCR2/5 antagonist cenicriviroc but failed to show a significant difference in the proportion of patients who achieved ≥ 1 stage reduction in fibrosis (without worsening of NASH) between cenicriviroc and placebo arms at Year 2.

The phase II NASH-CX study of galectin-3 inhibitor GR-MD-02 in patients with NASH, cirrhosis, and portal hypertension did not meet its primary endpoint of significant reduction in hepatic venous portal gradient (HVPG) at Week 54 in the overall population, but HVPG was significantly reduced in patient subsets without baseline esophageal varices or with a mild form of portal hypertension.

Early-stage clinical trial data showed significant liver fat reductions with ACC inhibitor GS-0976, THR-β agonist MGL-3196, and FGF19 analogue NGM282, but not with TLR-4 antagonist JKB-121, in patients with NASH.

Of importance, a phase II study assessing noncirrhotic patients with a presumptive diagnosis of NASH revealed significant reductions in MRI-PDFF with GS-0976 or FXR agonist GS-9674 alone but no additive reduction when these agents were combined with ASK1 inhibitor selonsertib. Moreover, selonsertib alone offered no reduction in MRI-PDFF.

Your Thoughts
In summary, ILC 2018 was an engaging meeting, especially for its encouraging efficacy data out of clinical trials in NASH. How will these and other new conference data influence your approach to managing patients with HCV or NASH? Lend your perspective in the comments section below or by answering the polling question at right.

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