The contemporary global burden of viral hepatitis is evident in 2015 WHO estimates, which recount 1.34 million deaths, 71 million people living with chronic HCV infection, and 257 million people living with chronic HBV infection.¹ Key data presented at the 2019 International Liver Congress (ILC) highlight progress and areas for improvement in the prevention and treatment of these infections.

Multiple short-course, once-daily regimens are now approved and recommended by international guidelines for the treatment of HCV infection. At ILC 2019, both randomized trial data and real-world observations reinforced the incredible efficacy and tolerability of these direct-acting antiviral (DAA) therapies. For instance, in a large English cohort with reported outcomes for more than 14,000 patients, the overall sustained virologic response (SVR) rate exceeded 95%.² Furthermore, across analyses dissected by regimen, comparably high SVR rates were demonstrated with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir in hard-to-treat genotype 3,² with elbasvir/grazoprevir or ledipasvir/sofosbuvir in genotype 1,³ and with sofosbuvir/velpatasvir/voxilaprevir in the salvage setting.⁴ Clinicians can be confident that cure is achievable—and safely achievable—in most patients with HCV infection.

However, to reach the goal of HCV elimination by 2030, as set forth in the Global Health Sector Strategy on viral hepatitis,⁵ merely having effective and safe drugs will not be enough. Conference data showed that substantial gaps in the HCV care cascade threaten progress toward elimination. Among nearly 1 million people identified as HCV antibody positive during retrospective analysis, just 54% received a confirmatory HCV RNA test.⁶ In addition, among those testing positive by antibody and RNA testing, a meager 11% were treated. Generalists and specialists alike failed to administer the proper tests and link patients to care. Proposed methods to mitigate these gaps included immediate treatment at diagnosis.

Conference data from Australia also reinforced that although rates of HCV testing and treatment may be high in key populations such as persons who inject drugs, particular subgroups within that population (eg, patients with high viremia, frequent injectors, women, those not receiving opioid substitution therapy) may need additional interventions to meet HCV elimination targets.⁷ Ultimately, adoption of an evolving approach that responds to the specific needs of patients will be critical moving forward.

In contrast to HCV infection, most treatments for chronic hepatitis B (CHB) must be continued indefinitely. Although promising early-phase data for multiple agents with novel mechanisms of action were reported at ILC 2019, entecavir (ETV), tenofovir alafenamide (TAF), and tenofovir disoproxil fumarate (TDF) top the list of currently preferred therapies for CHB. Of interest, the use of first-line TDF may be associated with a lower risk of hepatocellular carcinoma compared with ETV based on data from a Hong Kong cohort of more than 29,000 patients.⁸ Nevertheless, as expected, virologically suppressed patients receiving TDF demonstrated worse bone and renal outcomes over time compared with patients switching from TDF to TAF.⁹ When a stop is considered in patients with hepatitis B e antigen–negative CHB, data from a small randomized study suggest that particular subgroups may be at increased risk for alanine aminotransferase flares > 5 times the upper limit of normal, namely men and those with HBV DNA > 10,000 IU/mL 4-6 weeks following cessation of ETV or TDF.¹⁰

Finally, as in other recent liver meetings, nonalcoholic steatohepatitis (NASH) continued its prominence at ILC 2019. A leading cause of liver transplantation,¹¹ NASH currently has no approved treatment options, but many pharmaceuticals are under late-phase investigation. Widely anticipated results from the phase III REGENERATE trial were presented, demonstrating the ability of obeticholic acid to improve fibrosis at 18 months compared with placebo.¹² Pending longer-term positive data, a new drug application may be filed later this year. Further phase III data are anticipated for this disease and may breed additional submissions to the FDA in the future.

Detailed reporting of key data from the conference is available from multiple educational sources, such as Clinical Care Options’ conference coverage.