Fatty liver disease affects one in four in Europe

Image: Bru-nO/Pixabay

Non-alcoholic fatty liver disease affects one in four people in the general population in Europe and just over one in twenty people have advanced liver fibrosis, a meta-analysis of 33 studies from 15 European countries presented at the Digital International Liver Congress shows.

Non-alcoholic fatty liver disease (NAFLD) occurs when fat accumulates in the liver. People with diabetes or metabolic syndrome have a higher risk of developing NAFLD. Fat accumulation can lead to inflammation in the liver and damage (fibrosis). Liver damage due to fat accumulation is called non-alcoholic steatohepatitis (NASH).

NAFLD is a growing public health problem, but the prevalence is unclear. Studies have used differing methods to diagnose NAFLD, employing either blood tests or imaging to diagnose the condition.

The research team identified 19 studies including 42,580 people that diagnosed NAFLD by non-invasive imaging and nine studies including 84,235 people that assessed NAFLD prevalence by blood tests using the Fatty Liver Index. Twelve studies reported on the prevalence of NASH (4696 participants) and five on the prevalence of advanced fibrosis (7270 participants).

A meta-analysis of NAFLD prevalence studies found a pooled prevalence of 27%, with no difference in the result between studies which used imaging or blood tests to assess prevalence.

Studies assessing the prevalence of NASH were inevitably biased due to referral for biopsy based on clinical indication. Biopsy in NAFLD patients is usually recommended if there already is a suspicion of NASH, as examination of the liver tissue helps to differentiate between simple steatosis and steatohepatitis. The 12 studies found that 64% of 4696 NAFLD patients referred for biopsy had NASH.

Meta-analysis of five studies of advanced fibrosis prevalence in the general population found a prevalence of 6%. These studies used blood tests to assess the prevalence of F3 or F4 fibrosis (advanced fibrosis or cirrhosis).

The study authors say this is the largest analysis to date of the burden of NAFLD in Europe and needs to be followed up by an economic analysis of the potential benefits of non-invasive testing for advanced fibrosis in the general population, given the high prevalence detected across studies included in this meta-analysis.

Experimental treatments for NASH and NAFLD at the Digital International Liver Congress

Rohit Loomba presenting the firsocostat and cilofexor study results to EASL 2020.

Experimental treatments for non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) featured prominently in scientific sessions at the Digital International Liver Congress. Several drugs in mid-stage studies showed effects on various measures of liver damage and liver fat, although larger phase 3 studies will be needed to show whether these drugs can be used as treatments.

Aldafermin reduces bile acid production, limiting liver injury, and improves insulin sensitivity. It also reduces production of fatty acids and lipids that lead to fat deposition in the liver.

Aldafermin is being tested at several doses in a phase 2 study in people with NASH and F3/F4 fibrosis (advanced liver damage). Results from an arm of the study in which participants received 1mg of aldafermin by daily subcutaneous injection or placebo were presented at the conference.

After 24 weeks, liver fat content had fallen by 39% in the aldafermin group (from 18% to 10%) compared to 13% (19% to 15%) in the placebo group. Sixty-six per cent of people in the aldafermin group experienced a liver fat reduction of at least 30% compared to none in the placebo group. Twenty-two per cent of the aldafermin group experienced an improvement of at least one stage in fibrosis score and resolution of NASH compared to none in the placebo group.

Drug developer NGM Biopharmaceuticals is awaiting results of a study of a 24-week treatment course of a 3mg aldafermin dose to determine if a higher dose should proceed to phase 3 studies.

Cotadutide, an experimental therapy that alters glucose and lipid metabolism, led to weight loss and improvements in metabolic, cardiovascular and liver fibrosis biomarkers in overweight people with diabetes and fatty liver disease, but nausea was a common side effect, according to a phase 2b study presented at the conference.

NAFLD and its more severe form, NASH, are increasingly recognised as manifestations of the metabolic syndrome, characterised by abdominal obesity, high blood pressure, elevated blood sugar and abnormal cholesterol or triglyceride levels. Several treatments are targeting the underlying metabolic abnormalities to improve liver disease.

Cotadutide modifies the action of hormones that regulate glucose and lipid metabolism, liver fat build-up and bile acid production. Improving the activity of these hormones may reduce liver fat content.

The phase 2b study recruited 834 overweight or obese people with diabetes managed by metformin treatment. Participants were assigned to receive one of three doses of cotadutide or a daily dose of liraglutide (another diabetes medication) or a placebo.

After 54 weeks of treatment, people assigned to all three doses of cotadutide and liraglutide lost significantly more weight than those in the placebo arm. Those in the high-dose cotadutide group saw a weight reduction of 5%, which is considered clinically beneficial.

High-dose cotadutide treatment was also associated with a significant reduction in fibrosis score.

Nausea was a common side effect of cotadutide and 22% of people stopped taking the highest dose due to side effects. A phase II study of cotadutide for people with obesity and NASH is underway using an even higher dose with an optimised titration schedule – for example, a prolonged dosing interval – in an effort to reduce side effects.

Gilead Sciences has a pipeline of experimental treatments for NASH and has tested several in combination. Results of the phase 2b ATLAS trial were presented at the Digital International Liver Congress. The study tested three drugs – firsocostat, cilofexor and selonsertib – alone or in combination with another drug, compared to a placebo group.

None of the combinations tested achieved the primary outcome of the study – a significant improvement in fibrosis without worsening of NASH – but the combination of firsocostat and cilofexor did produce greater improvements in NAFLD as well as reductions in body weight and markers of liver injury. Although serious adverse events were rare in this study, itching was a frequent side effect, reported by 20-30% of participants according to treatment group, compared to 15% in the placebo group

Diabetes raises the risk of liver damage in people with HIV

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Almost half of people with HIV with unexplained liver enzyme elevations or other abnormal liver markers had non-alcoholic steatohepatitis (NASH) and 39 of 116 had stage F3 or F4 fibrosis, and advanced liver damage was strongly associated with type 2 diabetes, a four-country study reports in Clinical Infectious Diseases.

Fatty liver disease common in people living with HIV and hepatitis B

Around one in three people with HIV and hepatitis B had fatty liver disease and one in ten had liver damage, US researchers from the Hepatitis B Research Network report in Clinical Infectious Diseases.

They express concern about the additional harm that fatty liver disease may cause in people already at higher risk for fibrosis (liver damage).

Test and treat reduces hepatitis C by 83% in Melbourne gay men with HIV

Image: Jarun Ontakrai/Shutterstock.com/Pexels

Testing and treatment for hepatitis C in gay and bisexual men with HIV in Melbourne reduced the prevalence of the infection by 83% between 2012 and 2019, Australian researchers report in Clinical Infectious Diseases.

New hepatitis C infections also fell. One hundred and twelve new infections were detected at primary care sites during the study period. New infections fell by an average of 25% per year, from 27 in 2012 to 2 in 2019, with the greatest impact after 2015, when infections fell from 25 to 12 in one year.

The study authors say that their findings are probably applicable to other high-income settings where hepatitis C medication and access to health care is highly subsidised by government. Specialist nurse-led support was also important for achieving high treatment uptake. In this setting, a focused treatment programme achieved a rapid reduction in hepatitis C prevalence and incidence, suggesting that this level of support might only be needed for a few years.

Nobel Prize for hepatitis C discovery

Three scientists who discovered the hepatitis C virus have won the 2020 Nobel Prize for Medicine.

The winners are British scientist Michael Houghton and US researchers Harvey Alter and Charles Rice.

The Nobel Prize committee said their discoveries ultimately "saved millions of lives".

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