News from the 2020 AASLD Liver Meeting

This month's infohep bulletin highlights the key news from The Liver Meeting, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), which took place online from the 13 to 16 November.

Which people with chronic liver disease have higher COVID-19 risks?

Image: Gerd Altmann/Pixabay

Decompensated cirrhosis, alcoholic liver disease and hepatocellular carcinoma each raise the risk of death and severe illness from COVID-19 among people with chronic liver disease, but other liver conditions do not, a US multicentre study presented at the online AASLD Liver Meeting this month shows.

The findings come from one of the largest studies of COVID-19 outcomes in people with liver disease reported so far in the pandemic.

Previous studies have shown that cirrhosis raises the risk of liver injury after contracting COVID-19 and death from COVID-19.

Analysing COVID-19 outcomes in 867 people with chronic liver disease diagnosed with the infection in the United States, Nia Adeniji of Stanford University reported that 60% were admitted to hospital and 114 died.

The most common forms of liver disease in the study population were non-alcoholic fatty liver disease, affecting approximately 60% of cases; hepatitis C, affecting around 22%; alcoholic liver disease, present in 14%; and hepatitis B (7%).

Around 26% had cirrhosis. In almost 60%, cirrhosis was compensated.

Decompensated cirrhosis and alcoholic liver disease each raised the risk of death, hospitalisation, intensive care unit admission and mechanical ventilation. Hepatocellular carcinoma raised the risk of death but did not increase the risks of hospitalisation, ICU admission or ventilation.

Physicians should encourage the use of telemedicine in patients with chronic liver disease to reduce the risk of infection and chronic liver disease patients should be prioritised for vaccination, Nia Adeniji said.

Fatty liver greatly increases vulnerability to COVID-19 in obese people

Fatty liver disease combined with obesity places people at much higher risk of severe COVID-19, analysis of British people who tested positive for SARS-CoV-2 shows. Obesity alone did not increase the risk of being admitted to hospital with COVID-19 but obesity with high liver fat content doubled the risk of symptomatic illness and tripled the risk of being admitted to hospital with severe COVID-19 illness, Adriana Roca of Perspectum reported at the conference.

Obesity and fatty liver disease are closely intertwined. Obesity is an established risk factor for severe COVID-19 but fatty liver disease’s role as an independent risk factor for COVID-19 illness is unclear. Studies have produced conflicting results.

For example, a study in China found that fatty liver disease greatly increased the risk of developing severe COVID-19 in people admitted to hospital with symptoms.

But studies which looked at genetic markers of fatty liver disease in large population samples found no increase in risk of severe COVID-19.

Larger studies which can look at the relationship between liver fat content, body weight and COVID-19 risk are needed to provide more information.

Perspectum used data on liver fat content from UK Biobank participants to examine the relationship between obesity, liver fat and COVID-19 risk.

Of the 41,791 people who underwent liver scans, 931 had been tested for SARS-CoV-2 and 106 had tested positive. Of these, 48 had been hospitalised with COVID-19. People admitted to hospital because of severe illness were significantly more likely to be male, had a higher body mass index and were more likely to have fatty liver disease (defined as liver fat content > 5%).

When the researchers further broke down the study participants by liver fat content above or below 10%, they found that liver fat content of 10% or above was one of the strongest predictors of testing positive with COVID-19 symptoms and of hospitalisation with severe COVID-19. Body mass index raised the risk of symptomatic illness or hospitalisation far less.

Based on its analysis of liver disease in UK Biobank participants, Perspectum estimates that around 7.3 million people (11%) in the United Kingdom have both liver fat content of 10% or above and body mass index of 30 or above.

“This has huge implications both at the public health and socioeconomic levels,” said Adriana Roca. Treating fatty liver disease either through lifestyle interventions or upcoming therapeutic innovations should be considered, she said.

Minimal monitoring of hepatitis C treatment is safe and effective

Dr Sunil Solomon, Johns Hopkins University School of Medicine, presents results of the MINMON study. © The Liver Meeting Digital Experience™ 2020

Hepatitis C treatment with no monitoring visits during treatment is safe and leads to a high cure rate, an international study reported at the conference.

The MINMON study was designed to investigate how treatment might be delivered in lower-income settings as countries attempt to scale up access to direct-acting antiviral treatment for hepatitis C.

A "simple and safe" model of hepatitis C treatment that cuts monitoring and clinic visits to a minimum has the potential to expand the number of people who can be treated.

Study participants received a fixed-dose regimen of sofosbuvir/velpatasvir once daily for 12 weeks and attended the clinic twice: once to collect all study medication and give blood for laboratory tests and once to undergo viral load monitoring 12 weeks after completing treatment. Participants were contacted by phone at week 4 to check on adherence and possible side effects and once at week 22 to remind them of the post-treatment monitoring visit.

Ninety-five per cent of study participants achieved a sustained virologic response, or cure. There was no significant difference in response by sub-group except for an inferior response in people aged 20-29 years (8% of participants), in whom the cure rate fell to 85%.

Few countries will meet 2020 target for reducing viral hepatitis deaths

Abigail Adams of the Task Force for Global Health, Atlanta (bottom right) and the Liver Meeting Hepatitis C Epidemiology Panel © The Liver Meeting Digital Experience™ 2020

Around 1.1 million deaths were caused by viral hepatitis worldwide in 2019 and deaths due to hepatitis C are still rising despite the availability of direct-acting antiviral treatment, according to analyses of the Global Burden of Disease study presented this month at the online Liver Meeting.

The studies found that few countries are on course to meet interim targets for a 10% reduction of deaths due to viral hepatitis between 2015 and 2020, designed to encourage progress towards the goal of hepatitis elimination by 2030.

Only four countries – Lithuania, Moldova, Russia and Ukraine – are on course to meet that target for hepatitis C.

Twenty-five countries are on track to meet the 2020 interim target for hepatitis B, chiefly in central and west Africa. Bangladesh, India and Russia will also meet the target.

Deaths due to hepatitis C are highly concentrated; 20 countries account for 76% of global deaths from hepatitis C and within this group of 20, more than half of all global deaths from hepatitis C occurred in five countries – China, India, the United States, Japan and Egypt.

Deaths from hepatitis B are also highly concentrated. Twenty countries accounted for 81% of deaths in 2019 and two countries – China and India – accounted for more than half of all deaths due to hepatitis B worldwide.

Few countries with a high burden of hepatitis B-related deaths are on track to meet the 2020 interim target and most have seen increases in deaths of between 5 and 11% since 2015. Only two high burden countries – Democratic Republic of Congo and Russia – are on track to meet the 2020 targets.

Can investment in hepatitis C treatment be cost saving?

Madeline Adee, Massachusetts General Hospital Institute for Technology Assessment. © The Liver Meeting Digital Experience™ 2020

Direct-acting antiviral treatment for hepatitis C can be cost saving for some countries within five to ten years, especially if they can negotiate lower drug prices, a study presented at the conference shows.

Madeline Adee of Massachusetts General Hospital Institute for Technology Assessment presented results of a 158-country comparative study of the cost-saving impact of direct-acting antiviral treatment for hepatitis C.

Based on data supplied to the researchers, only eleven countries have achieved direct-acting antiviral prices that would lead to treatment being cost saving in five years, including Chile, Belarus, Kazakhstan, Ukraine, India and Pakistan. Few countries had achieved prices that would enable treatment to become cost saving within ten years.

Comparing countries, the study found that whereas treatment in higher-income countries (western Europe, North America, Australasia, South Korea and Japan) would be cost saving within five years at a treatment cost between $2001 and $9500 per treatment course, treatment in upper-middle income countries including Argentina, Chile, Mexico, Turkey, Russia and Malaysia would need to be priced between $1001 and $2000 per course for the expenditure to be cost saving within five years.

For China, Iran and Thailand – countries with a high prevalence of hepatitis C – treatment would need to be priced between $501 and $1000 to be cost saving. Several large middle-income countries with high burdens of hepatitis C – Brazil, Egypt, India, Indonesia and Ukraine – would need to pay between $150 and $500 for treatment to be cost saving.

Tenofovir alafenamide prevents mother-to-child hepatitis B virus transmission

Image: Helen Sushitskaya/

Tenofovir alafenamide (TAF; Vemlidy) is highly effective at preventing transmission of hepatitis B virus (HBV) from mothers with a high viral load to their infants, according to a pair of studies presented at the conference.

Mother-to-child transmission is the most common route of HBV infection worldwide. The risk of transmission ranges from 70 to 90% for mothers who have a high viral load or are hepatitis B 'e' antigen positive (HBeAg), according to the World Health Organization (WHO).

WHO recently updated its guidelines for prevention of perinatal HBV transmission, and now conditionally recommends that pregnant women with a high viral load (200,000 IU/ml or greater) should receive tenofovir prophylaxis from the 28th week of gestation at least until the time of delivery.

TAF is a newer formulation of tenofovir that causes less kidney and bone toxicity than TDF (tenofovir disoproxil fumarate).

In both studies TAF reduced hepatitis B DNA levels, no cases of hepatitis B transmission were observed, and no serious adverse events were reported in mothers or infants.

Although both studies showed that TAF is safe and effective for preventing mother-to-child transmission, cost may limit its use. TAF, from Gilead Sciences, is still under patent, while generic versions of TDF are available in many countries for around £2 (US$3).

Some hepatitis B patients can safely stop antivirals

Many people who take nucleoside/nucleotide antivirals for chronic hepatitis B can safely discontinue treatment, although this usually does not lead to a cure, researchers reported at the conference.

Treatment guidelines disagree about when it is appropriate to stop treatment. Both AASLD and EASL guidelines state that HBeAg-positive patients can consider discontinuation if they experience HBeAg seroconversion and have undetectable hepatitis B virus (HBV) DNA for at least six to 12 months, but relapse is common. For HBeAg-negative patients, AASLD recommends stopping only after HBsAg loss, while EASL guidelines say treatment can be discontinued after three years in those with viral suppression if close monitoring can be guaranteed.

Two studies presented at The Liver Meeting looked at outcomes in people who stopped antiviral treatment.

Prof. Norah Terrault of the University of Southern California reported on outcomes in a study comparing treatment with tenofovir to treatment with tenofovir and pegylated alfa interferon. After four years of antiviral treatment, participants were eligible to stop treatment if they had low HBV DNA, no cirrhosis and were HBeAg negative. Participants resumed treatment if they had prolonged liver enzyme elevations, increases in HBV viral load or decompensation of cirrhosis.

One hundred and five people were eligible to discontinue treatment after four years and after 48 weeks of follow-up off treatment, 30% of participants in the monotherapy group and 39% in the combination therapy group who stopped treatment were considered to have inactive chronic hepatitis B.

A second study of 1337 people with chronic hepatitis B, treated with tenofovir or entecavir for a median of six years, found that 47 people stopped treatment.

Six people restarted antivirals due to viral load rebound (above 2000 IU/ml) or ALT flares (more than twice the upper limit of normal). Only one person in this group experienced HBsAg loss.

The two studies suggest that withdrawal of antiviral treatment after four years of therapy can be safely achieved in most people who meet the criteria for stopping, the investigators concluded.

NASVAC therapeutic vaccine may lead to functional cure of hepatitis B

NASVAC, an experimental therapeutic vaccine that targets two different hepatitis B virus (HBV) antigens, led to a reduction in hepatitis B surface antigen levels and several study participants achieved a functional cure after 18 months of follow-up, according to a report at the conference.

Unlike the widely used vaccines for hepatitis B prevention, NASVAC aims to treat people who already have chronic HBV infection. The nasally administered vaccine contains both hepatitis B surface antigen (HBsAg) and core antigen (HBcAg). The combination triggers the production of anti-HBs antibodies and promotes T-cell activity against the virus.

The study reported 18-month follow-up on 55 people who had received ten doses of the vaccine. Participants experienced modest reductions in HBsAg and six people experienced HBsAg loss by 18 months, a functional cure for hepatitis B infection.

"Nasal administration of NASVAC could be an effective and safe immune therapy for achieving functional cure" in chronic hepatitis B patients, the researchers concluded.

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