News from The Liver Meeting

This month’s infohep bulletin focuses on news from The Liver Meeting 2018, organised by the American Association for the Study of Liver Diseases (AASLD), which took place in San Francisco, USA, from 9 to 13 November 2018.

Aspirin reduces liver cancer risk

Dr Tracey Simon at The Liver Meeting 2018. Photo by Liz Highleyman.

Taking aspirin about twice a week for five years or more may reduce the risk of developing hepatocellular carcinoma (HCC) by about half, according to research presented at the AASLD Liver Meeting in San Francisco.

Daily low-dose aspirin, recommended to prevent cardiovascular disease in those at high risk, has also been shown to lower the risk of colorectal cancer. It also appears to reduce the likelihood of developing other types of cancer. But regular aspirin use also carries risks, including gastrointestinal bleeding.

An analysis of 133,371 people in the United States who reported on their use of aspirin found that taking at least 325mg of aspirin twice a week was associated with a 49% reduction in the risk of liver cancer. A significant benefit of aspirin was apparent after five or more years of use at an average dose of at least 1.5 tablets per week, the researchers concluded.

Aspiring might reduce the risk of liver cancer by delaying fibrosis, by direct inhibition of cancer development or by reducing fat accumulation in the liver, the researchers suggest.

Sofosbuvir/ledipasvir for children aged three to six years

Kathleen Schwarz at The Liver Meeting 2018. Photo by Liz Highleyman.

Treatment with sofosbuvir and ledipasvir granules that can be mixed with food or sprinkled on the tongue cured hepatitis C in all but one of 34 children aged three to six years, Kathleen Schwarz of Johns Hopkins Hospital reported at the conference. The success of the new formulation means that treatment will soon be available for younger children with hepatitis C.

Hepatitis C in rectal and nasal fluid

High levels of hepatitis C virus (HCV) can be found in the rectal and nasal fluids of people with high hepatitis C viral loads even when blood is not present, Austrian researchers reported at the conference.

The findings reinforce the plausibility of HCV transmission through sharing of rolled-up bank notes or other equipment for snorting drugs. The findings also show that HCV can be transmitted during anal intercourse even when blood is not present.

The study found that 70% of participants gave at least one sample of nasal or rectal fluid that was positive for HCV RNA. The presence of HCV RNA in a sample was associated with having a higher viral load in blood but was not dependent on HIV status, on recent HCV infection or on possible route of acquisition.

Diabetes, stroke and cancer incidence fall after hepatitis C cure

The incidence of some of the most serious extrahepatic health problems caused by hepatitis C declines sharply after the infection is cured by antiviral treatment, a review of people treated for hepatitis C in the Canadian province of British Columbia has found.

Hepatitis C infection is associated with a higher incidence of chronic kidney disease, diabetes and cardiovascular disease. Curing hepatitis C might reduce the incidence of these health problems, but the impact of treatment has been unclear.

Researchers from the British Columbia Hepatitis Testers Cohort looked at the outcomes of 73,000 people who tested positive for hepatitis C between 1999 and 2014 in the province. They found that after ten years of follow-up, rates of diabetes and mood and anxiety disorders were 47% and 29% lower in people cured of hepatitis C. The incidence of stroke was 33% lower and the incidence of chronic kidney disease was 52% lower than in people not cured of hepatitis C, although in both cases the overall incidence of the condition was much lower than the incidence of diabetes or mood disorder.

8-week Maviret in cirrhosis

An 8-week course of the combination of glecaprevir and pibrentasvir (Maviret) is highly effective in curing hepatitis C in people with compensated cirrhosis, across a wide range of genotypes, Robert S. Brown of Weill Cornell Medical College reported at the conference.

Reducing the duration of treatment to eight weeks saves money and makes it easier for people to adhere to a course of treatment, so all companies developing and marketing drugs for hepatitis C have been striving to show that their products can deliver high rates of cure after eight weeks.

The EXPEDITION-8 study recruited people with early-stage compensated cirrhosis with any genotype of hepatitis C apart from genotype 3 (a genotype 3 arm of the study is now underway). Participants received eight weeks of treatment and 98% of those enrolled in the study had a sustained virologic response. As Maviret contains a protease inhibitor, it is approved for use in compensated but not decompensated cirrhosis.

NAFLD and cancer risk

Alina Allen at The Liver Meeting 2018. Photo by Liz Highleyman.

People with non-alcoholic fatty liver disease (NAFLD) were found to have higher rates of cancer, with the greatest increase observed for gastrointestinal cancers, according to findings presented at the conference. These findings suggest that NAFLD may be a key driver of the increased risk of cancer associated with obesity.

The study compared cancer rates among 4791 adults diagnosed with NAFLD in a Minnesota county between 1997 and 2018 and a general population control group of 14,432 people matched by age and sex. Individuals with viral hepatitis and other causes of liver disease were excluded.

The overall risk of cancer was 91% greater in the NAFLD group compared with the control group. The researchers also asked whether fatty liver disease is associated with a greater risk of cancer than obesity in the absence of NAFLD. They found that people with NAFLD had a significantly higher risk compared with obese people in the control group without NAFLD. In fact, obesity was associated with a higher cancer risk only in those with NAFLD, not in those without.

Study investigator Dr Alina Allen of the Mayo Clinic in Rochester said: "Liver cancer had the highest increase in relative risk, and this was not a surprising finding. However, the 2.5-fold higher risk of stomach and pancreatic cancer are novel data that the medical community should be aware of. Future studies should further examine this association to determine if screening methods should be implemented in this population."

Experimental treatments for NASH and NAFLD

Rohit Loomba at The Liver Meeting 2018. Photo by Liz Highleyman.

Thyroid hormone activation appears to be a promising approach for treating fatty liver disease, according to a pair of studies presented at the conference.

Thyroid hormones play an important role in metabolism, and agents that promote thyroid hormone receptor-beta activity can reduce blood lipid levels and reduce liver fat by breaking down fatty acids.

Two thyroid hormone receptor beta agonists – MGL-3196 and VK2809 – reduced liver fat and blood lipid levels in people with non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH).

A phase 2 study of MGL-3196 showed that people who received 12 weeks of treatment showed a 49% reduction in liver fat 24 weeks after stopping treatment if they received the higher dose of the drug. Lipid levels and liver inflammation declined, and loss of liver fat was associated with weight loss.

Looking at liver damage, one-third of participants experienced a 1-stage regression in liver fibrosis and 27% of the MGL-3196 recipients experienced resolution of NASH.

Another agent, VK2809, produced a 'robust' reduction in liver fat after 12 weeks of treatment. Ninety-one per cent of a group of 47 people with NAFLD experienced a reduction in liver fat of at least 30%.

Nivolumab for liver cancer

Masatoshi Kudo at The Liver Meeting 2018. Photo by Liz Highleyman.

Nivolumab (Opdivo), a checkpoint inhibitor that helps the immune system fight cancer, was associated with tumour shrinkage or disease stabilisation in 55% of hepatocellular carcinoma (HCC) patients with substantial liver function impairment, according to a presentation at the conference.

Nivolumab is a monoclonal antibody that blocks the PD-1 receptor on T-cells, an immune checkpoint that plays a role in regulating immune function.

The US Food and Drug Administration approved nivolumab for liver cancer last year and another PD-1 checkpoint inhibitor, pembrolizumab (Keytruda), earlier this month. The European Medicines Agency has approved both drugs for several types of cancer, but not yet for HCC.

The study presented at The Liver Meeting looked at responses to nivolumab in 49 people with liver cancer and Child-Pugh B cirrhosis. The study found that liver cancer stabilised in 45% of people treated after a median follow-up period of 12 months.

HCV treatment in people who inject drugs

Providing hepatitis C virus (HCV) therapy with direct-acting antivirals (DAAs) to people who inject drugs can achieve rapid reductions in community prevalence of viraemia, according to Australian research published in the Journal of Hepatology. Uptake of HCV treatment increased from 10% to 41% after unrestricted access to DAAs was rolled out in March 2016, and the proportion of viraemic patients fell from 43% to 25%.

The authors believe their findings have significance for the World Health Organization target of eliminating HCV as a public health threat by 2030.

“The elimination of HCV as a global public health threat will require strategies that provide DAA access to high-risk populations, often those who are highly marginalised in society,” comment the investigators. “This study provides evidence that relatively high rates of HCV treatment can be achieved among PWID [people who inject drugs] when DAA therapy is made available without restriction.”

Glecaprevir/pibrentasvir licensed to the Medicines Patent Pool

The Medicines Patent Pool has agreed a new, royalty-free licence with AbbVie for glecaprevir/pibrentasvir (G/P) – a World Health Organization-recommended treatment for people living with chronic hepatitis C (HCV). The licence will enable quality-assured manufacturers to develop and sell generic medicines containing G/P in 99 low- and middle-income countries and territories at affordable prices, enabling access to and treatment scale-up with the most effective pan-genotypic regimens.

Although the licence covers several countries with very high burdens of hepatitis C, notably Egypt, Indonesia, Pakistan and Vietnam, concerns have been raised about the exclusion of India.

“Excluding countries with more capacity to finance reasonably priced HCV elimination strategies shrinks the overall market for generic G/P, reduces economies-of-scale for generic producers, and thus undermines treatment and elimination strategies in licensed territories as well,” said Brook Baker of Health GAP in a commentary on the licence.

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