This month’s infohep bulletin focuses on news from The Liver Meeting 2017, organised by the American Association for the Study of Liver Diseases (AASLD), which took place in Washington DC, USA, from 20 to 24 October 2017.

Zobair Younossi presenting at The Liver Meeting 2017. Photo by Liz Highleyman, hivandhepatitis.com

People who were cured of hepatitis C with direct-acting antivirals had sustained improvements in their health-related quality of life, including both physical and mental health measures, according to study results presented at The Liver Meeting last month.

A study of all people who were cured of hepatitis C in clinical trials of sofosbuvir-based treatment found that participants experienced significant improvements in aspects of quality of life such as pain, physical activity, vitality, mental and emotional health and social interaction.

Quality of life scores began to improve during treatment and continued to improve after the completion of treatment. The improvement in quality of life was sustained throughout the three-year follow-up period.

These findings have important policy implications, showing that "treatment is not only about clinical benefit, but also about the patient experience," said presenter Zobair Younossi of Inova Fairfax Hospital in Virginia.

Hooman Farhang Zangneh presenting at The Liver Meeting 2017. Photo by Liz Highleyman, hivandhepatitis.com

Hepatitis C virus (HCV) is readily transmitted through shared needles and people who inject drugs have high rates of HCV incidence (new infections) and prevalence (total existing infections). HCV prevention and treatment for current and former drug users was a key theme at The Liver Meeting, especially in the context of growing opioid epidemics in North America and elsewhere.

People who inject drugs make up a large proportion of those living with hepatitis C – and of those who will need to be treated in order to eliminate HCV as a public health threat. However, many of these individuals have not been tested and do not know their HCV status. Addiction treatment programmes, such as those that provide opioid substitution therapy using methadone or buprenorphine, offer a potential entry point into hepatitis C care.

Getting tested for HCV was associated with reduced drug use, especially among those who tested positive, but even people who tested negative saw some reduction, according to study results presented at the conference.

After adjusting for other factors in a multivariate analysis, people who tested HCV positive were 33% more likely to lower their use of non-prescription opioids, compared with those who tested HCV negative. People diagnosed with HCV were also about 50% more likely to decrease their use of benzodiazepines and cocaine.

Alina Allen presenting at The Liver Meeting 2017. Photo by Liz Highleyman, hivandhepatitis.com

Non-alcoholic fatty liver disease (NAFLD), and its more severe form non-alcoholic steatohepatitis (NASH), refer to the build-up of fat in the liver in people who do not drink heavily. Fatty liver disease, which is often associated with obesity and metabolic syndrome, is now the most common chronic liver disease worldwide. Over time, fat accumulation in the liver and the accompanying inflammation and build-up of scar tissue (fibrosis and cirrhosis) can interfere with normal liver function and lead to liver cancer.

Fatty liver disease is also associated with a higher risk of cardiovascular events – and in fact people with NAFLD are more likely to die of heart disease than of liver disease.

Women with NAFLD had a higher risk of cardiovascular events including chest pain and heart failure compared to women without the condition – and about the same risk as men with NAFLD – in a study presented at The Liver Meeting.

The researchers calculated that a 50-year-old woman with fatty liver disease had about the same cardiovascular risk as a 53-year-old man with NAFLD, a 58-year-old man without NAFLD or a 67-year-old woman without NAFLD.

Treatment for liver fat accumulation is still experimental and it is unclear if any experimental treatments will have an impact on the long-term health of people with NAFLD or NASH.

Several pharmaceutical companies are developing drugs to treat NASH. At The Liver Meeting, Gilead Sciences presented results of a phase 2 study of GS-0976, a drug designed to interrupt a step in the conversion of carbohydrates into fatty acids in the liver.

The randomised placebo-controlled study recruited people with NAFLD who had evidence of liver fat accumulation and/or F1-F3 stage fibrosis. The study showed that people who received GS-0976 experienced significant reductions in liver fat accumulation and fibrosis. However, triglyceride levels also rose modestly in people who received the drug and longer-term follow-up will be needed to understand the effects of these changes.

George Iaonnou presenting at The Liver Meeting 2017. Photo by Liz Highleyman, hivandhepatitis.com

People who achieved a sustained response to hepatitis C treatment lowered their risk of hepatocellular carcinoma (HCC) by around 70%, regardless of whether they were treated with new direct-acting antivirals (DAAs) or older interferon-based therapy, according to study results presented at The Liver Meeting.

The findings come from the largest cohort of people treated for hepatitis C: 62,354 people in the hospitals run by the US Department of Veterans Affairs.

After adjusting for more than 20 factors including demographics, hepatitis C virus genotype, HIV or hepatitis B co-infection and liver disease severity, sustained virologic response to treatment was associated with a 68% decline in the risk of new HCC among people without cirrhosis and a 50% reduction among those with cirrhosis.

The findings confirm the results of several other large studies which showed that treatment with DAAs is not associated with an increased risk of liver cancer in people with no prior history of liver cancer. This study does not address the question of whether DAA treatment increases the risk of recurrence of HCC, as several previous studies have indicated.

A second study, in Taiwanese people with chronic hepatitis B infection, showed that the risk of developing liver cancer was reduced by 37% over a follow-up period of four years in people who took aspirin daily. The population was largely untreated for hepatitis B and only 5% had advanced liver disease (cirrhosis).

Aspirin is recommended as a preventative treatment in people at higher risk for cardiovascular disease, and to reduce the risk of colon cancer, in US guidelines. Other countries have been more cautious in recommending aspirin for primary prevention of cardiovascular disease owing to the risk of gastrointestinal bleeding.

A large study carried out by researchers in Hong Kong, of 600,000 people followed for an average of seven years, found that daily aspirin use reduced the risk of liver cancer by 47% and also reduced the risk of other cancers of the digestive system. The study was conducted in the general population. The findings were presented this week at the 25th United European Gastroenterology Week in Barcelona.

At present, there is no recommendation regarding the use of aspirin for the prevention of liver cancer and further analysis of these results will be needed before any recommendation is made by professional bodies. It’s important to be aware that the daily use of even a low dose of aspirin carries a small, but not negligible, risk of gastrointestinal bleeding.

Juan Berenguer and Juan González from GeSIDA at EACS 2017. Image credit: @GeSIDA

Elimination of hepatitis C will depend on high levels of diagnosis and access to treatment, as well as engagement in care of people with hepatitis C. People living with HIV have high levels of engagement in care for long-term management of HIV infection. New research from Spain and Switzerland shows that among people with HIV, hepatitis C elimination is possible if treatment is accessible.

At last week’s 16th European AIDS Conference, organised by the European AIDS Clinical Society (EACS) and held in Milan, Italy, Dr Juan Berenguer reported on declining hepatitis C virus (HCV) prevalence among people living with HIV in Spain. Sampling HIV clinic cohorts throughout Spain, Berenguer and colleagues found that the prevalence of chronic hepatitis C infection has almost halved from late 2015 to late 2016 from 22% to 11.6%. The decline coincides with the offer of direct-acting antiviral treatment for hepatitis C to everyone with F2 grade fibrosis or above since early 2016 and provision of direct-acting antiviral treatment to anyone who might transmit HCV, regardless of fibrosis stage.

A systematic policy of test-and-treat cured 99% of men who have sex with men with hepatitis C in the Swiss HIV Cohort in an 8-month period and reduced the prevalence of hepatitis C by almost two-thirds, Dominique Braun of the University Hospital, Zurich, reported at the conference.

The Swiss HIV Cohort set out to identify all men who have sex with men with hepatitis C and HIV, in order to cure as many men as possible from hepatitis C and reduce the sexual transmission of this virus between men in Switzerland. In common with other countries in Western Europe, Switzerland has seen a large increase in hepatitis C infection among gay and bisexual men with HIV since the mid-2000s. This increase is due in part to the increased use of drugs such as injectable methamphetamine during sex, but also to condomless sex.

Screening in 2015 identified 177 men with chronic HCV infection (4.8% of the men who have sex with men in the cohort) of which 147 had been diagnosed previously. All men with genotype 1 or 4 infection were offered immediate treatment with a course of grazoprevir/elbasvir (Zepatier) for 12 or 16 weeks. Ninety-nine per cent were cured of hepatitis C.

In principle, reinfection with hepatitis C is always possible, because cure of the virus does not create any immunity. Therefore, study participants were also invited to take part in a behavioural intervention designed to reduce the risk of reinfection, by examining sexual behaviour and helping participants to identify risk reduction strategies to avoid reinfection. So far, no cases of reinfection have been identified in this study cohort.

Intellectual property lawyers and advocates in the United States have filed legal challenge to Gilead’s patents on its hepatitis C drug sofosbuvir, I-MAK announced last week. The challenge contends that the drug’s six core patents do not meet the legal standards for novelty and non-obviousness. In particular, the lawyers argue that sofosbuvir was not a new type of drug and its structure closely resembled many other drugs of the same type. Very little inventiveness was required to create sofosbuvir and the company is being rewarded for its good luck in identifying a highly effective compound rather than any originality or inventiveness, the lawyers argue.

I-MAK says that unjustified patent protections prevent generic versions of sofosbuvir from being sold in the United States.

Steven Flamm presenting at The Liver Meeting 2017. Photo by Liz Highleyman, hivandhepatitis.com

Glecaprevir and pibrentasvir, the two drugs in the recently approved Maviret co-formulation, demonstrated high sustained response rates for people with chronic hepatitis C virus genotype 3 and for people with liver cirrhosis, two studies presented at The Liver Meeting show.

An integrated analysis of clinical trial data showed that glecaprevir/pibrentasvir taken for 8 weeks cured 98% of people without cirrhosis with hard-to-treat genotype 3, while a 12-week course cured 100% of people with genotype 3 with cirrhosis. A related analysis showed that the combination taken for 12 or 16 weeks cured 96% of people with compensated cirrhosis across all genotypes.

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