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LIVER DISEASE “We also found that, if the MELD-Na


score had been used to prioritise patients instead of the MELD score, 26.3% of those who died within 90 days would have had a significantly higher chance of receiving a liver transplant,” he said. “This equates to a 4.9% reduction in 90-day waiting-list mortality.” The researchers believe that, as there is a shortage of liver grafts and the prevalence of cirrhosis is increasing globally, better prediction of mortality and improved prioritisation for liver transplantation are becoming increasingly important. “We believe that MELD-Na-based allocation would help to prioritise patients on European liver transplant waiting lists and reduce the number of patients who die before they receive this life-saving treatment. The MELD score was a breakthrough in the field of liver transplantation, as it ensured equity in patients assessed and listed for a transplant. Over the years, it became apparent that the addition of sodium to the original equation improved the classification of patients, and the MELD-Na was subsequently adopted in the USA in 2016,” explained Professor Emmanuel Tsochatzis. “This study is an important step in introducing MELD-Na in the European liver transplant programmes, as it demonstrated an almost 5% improvement in 90-day waiting list mortality.”


Treatment of chronic hepatitis B virus Progress towards finding a cure for chronic hepatitis B virus (HBV) infection was also showcased at this year’s Digital International Liver Congress. Recent results from studies of several novel agents designed to achieve a functional cure for this chronic liver disease were presented to scientists from around the


One in four patients diagnosed in hospital with severe liver disease in England and Wales die within 60 days because of late diagnosis


world. While many of these early trials focused on safety and tolerability, they also showed some promising signs of progress in combating HBV infection. Chronic HBV infection continues to exert a heavy toll worldwide, despite the availability of effective vaccines and improved treatments. Two classes of drug are currently approved for the treatment of HBV: nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and interferon-alpha (IFNα). These treatments can achieve viral suppression but rarely result in the loss of hepatitis B surface antigen (HBsAg), which is considered to be a ‘functional’ cure and the aspirational goal of HBV treatment. To date, no single agent or combination of treatments has achieved that goal. The emerging therapies discussed at the event exploit novel mechanisms of action to try and bring us closer to a cure, by disrupting the production of viral proteins such as HBsAg, inhibiting the HBV core protein directly, and targeting the immune system in order to control HBV.


Targeting the production of viral proteins A total of four studies presented at the Congress evaluated this strategy for HBV, either using RNA interference (RNAi) or antisense oligonucleotides to inhibit the ability of the virus to synthesise the components it needs to replicate. Two studies involved the combination


of NRTIs with novel RNAi therapies: JNJ-3989 (Arrowhead Pharmaceuticals/ Janssen) and VIR-2218 (Vir Biotechnology/


Alnylam Pharmaceuticals). In the first study, 40 patients with chronic HBV were treated with NRTIs plus three monthly doses of subcutaneous JNJ-3989 (100 mg, 200 mg, 300 mg or 400 mg). At the HBsAg nadir, 39/40 (97.5%) patients achieved a ≥1 log10 IU/mL reduction from Day 1 HBsAg values, and 22 (56%) of these had sustained HBsAg reductions (≥1 log10 IU/mL) approximately nine months after the last dose of JNJ-3989. In the second ongoing study, 24 patients with chronic HBV received NRTIs plus two subcutaneous injections of VIR-2218 at various doses. A subset of patients who received the 50-mg dose achieved maximal reductions in HBsAg at Week 12, with a mean reduction of 1.5 log10 IU/mL from baseline. A mean reduction from baseline in HBsAg of 1.0 log10 IU/mL was maintained through Week 28 in this cohort, and the therapy was generally well-tolerated without clinically significant ALT elevations. Two novel antisense oligonucleotides


were also presented at the Congress: ISIS 505358/GSK3228836 (Ionis Pharmaceuticals/GlaxoSmithKline) and RO7062931 (Roche). They produced reductions in HBsAg in an early-phase clinical trial in patients with chronic HBV.


Hepatitis B virus. Chronic infection continues to exert a heavy toll worldwide, despite the availability of effective vaccines and improved treatments (transmission electron micrograph [TEM]).


WWW.PATHOLOGYINPRACTICE.COM DECEMBER 2020


Targeting the HBV core protein Another way of inhibiting the virus is to target its component proteins directly. This strategy was used in a study involving 26 patients with HBeAg-negative chronic hepatitis B who were virologically suppressed after a mean duration of four years of NRTI therapy. In the study, in addition to maintaining their NRTI, patients were randomised to receive either the novel oral HBV core inhibitor ABI-H0731 (300 mg once daily; Assembly Biosciences) or placebo for 24 weeks. At Week 24, ABI-H0731 produced deeper viral suppression with an increase in the percentage of patients with HBV DNA <5 IU/mL (undetectable using sensitive polymerase chain reaction [PCR] methodology) from baseline (63% of patients at baseline vs. 94% at Week 24 compared with 80% vs. 70% with placebo). In this virologically suppressed population, HBsAg levels were not significantly changed from baseline in both treatment groups. Overall, ABI- H0731 was generally safe and well- tolerated.


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