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Non-Alcoholic Steatohepatitis: A Lesser-Known Global Plague

Charlie Goode by Charlie Goode
February 8, 2023
in Health
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Non-Alcoholic Steatohepatitis: A Lesser-Known Global Plague

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NASH (Non-alcoholic Steatohepatitis) is the progressive, more dangerous form of Non-alcoholic fatty liver disease (NAFLD). There is little public knowledge of the prevalence of NASH and little understanding of the risks, but pharmaceutical companies have begun to run awareness campaigns to advance early diagnosis. Some health firms specialising in dietary and hygiene therapies may also hold the key to fighting the disease.

Over the next decade or so, it is believed that a global liver disease pandemic will materialise. Professor Dina Tiniakos, a pathologist at the National and Kapodistrian University of Athens, believes that cases of acute liver disease will have exploded by the end of the decade, and predicts that there will be around 800,000 NASH-related deaths by 2030, based on the latest studies of liver diseases. This public health crisis could cost billions for health economies, and raising awareness and developing solutions quickly will be key if the worst is to be avoided. Collaboration between different health services will be essential.

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What is NASH?

A build-up of fat around and into the liver (a “fatty liver”), is common, and, for most people, causes no adverse health effects and no symptoms in the early stages of the disease. However, in the longer term, it can cause inflammation and damage to cells in the liver, meaning the organ stops functioning as it should. NASH is a progressive form of the condition and, if left untreated, can result in serious health problems such as cirrhosis or liver cancer.

There is no general consensus about what causes NASH, why some people suffer from it and why others do not. Although genetic factors certainly need to be considered, the most common denominators found in NASH patients are linked to lifestyle or dietary health issues including obesity, diabetes and insulin resistance, high blood cholesterol and/or triglycerides levels, or metabolic syndrome. To check for NASH, doctors can test patients for the build-up of fat around the liver through blood checks, MRI scans, CT scans, or abdominal ultrasounds. If there is a greater risk to the patient, a liver biopsy may also be performed.

NASH has become a worldwide problem. In the United States, it is estimated that a third of the population lives with NAFLD, which has the potential to pose serious health risks later in life. Of those with NAFLD, about 5% develop NASH. In Europe, it is predicted as many as 25% of the population suffers from NASH. There is a palpable increase in cardiovascular mortality rates in people found to have developed NASH and NASH-related cirrhosis is a risk factor for hepatocellular cancer. NAFLD is therefore a common condition that can have significant adverse health consequences for those who are afflicted. It is a major public health hazard around the globe.

The search for solutions

Treating NASH involves real lifestyle changes focused on diet and weight loss, or in other words, trying to manage the different conditions that make NASH worse. This means, above all, reaching a healthier weight by losing at least 10% of your total body weight. Numerous studies have demonstrated that such a weight loss can help to normalize blood lipid levels and controlling diabetes. This measure should of course also be associated with the reduction of alcohol consumption, and regular exercise.

Of course, pharmaceutical companies have been rushing to find new solutions to tackling the condition, which is spreading at an alarming rate in an increasingly obese world. Danish biopharma firm Novo Nordisk is one such player making roads into NASH research. Back in 2020, after the failure of French biotech Genfit’s phase III trial of its lead drug candidate elafibranor, Novo Nordisk ran its phase II trial of its type 2 diabetes drug semaglutide for the treatment of NASH. “The results from this phase II trial show that semaglutide has effects on disease severity, can resolve the disease in a significant proportion of patients with NASH, and has the potential to address a large unmet medical need,” said Stephen Gough, Global Chief Medical Officer at the firm.

Although this stage II trial eventually failed, the company is persevering in its attempts to combat NASH head-on. “The development of semaglutide in NASH is very much still on track and actually in phase 3,” said a Novo Nordisk spokesman. “In August 2020, the FDA granted breakthrough therapy designation for semaglutide in NASH, and in April 2021, we initiated the phase 3 program Essence.”

Although promising, a solution for tackling NASH would undoubtedly involve not only medicinal innovations but lifestyle, dietary, and nutritional changes, encouraging those at risk to first get down to a healthy weight in order to offset the higher risk of fat build-up around the liver. In any case, if one day a new drug is authorized to fight the disease, the prescription recommendations will certainly include an application of hygiene and dietary rules (weight loss and practice of regular physical exercise) for a period of at least 6 months, before the start of treatment. Moreover, none of these drugs will be effective unless the treatment is combined with lifestyle changes. Some companies, such as the French firm Groupe Ethique & Santé, have teamed up with doctors to develop a modern and innovative approach to weight loss and dietary guidance. The programme, known as RNPC, could well be an ally to pharmaceutical corporations, in the fight against NASH.

Programme Director of the Novo Nordisk Foundation and member of the RNPC scientific committee, Arne Astrup, has long advocated for and promoted healthy weight among children and adolescents in order to encourage societal change. “It is an important task with great societal impact, which requires the involvement of all relevant actors in the field when developing the initiative,” he said. Professor Astrup has himself advocated the efficacy of the RNPC programme, which is centered on a personalised approach to nutritional education in order to prevent the aggravation of liver- or heart-related diseases. RNPC is a fully-fledged therapy, only available to patients who have obtained the agreement of their GP. A two-pronged approach may be the best way forward…

Tackling NASH will be one of the biggest challenges facing the health sector in the years to come. Taking advantage of scientifically-proven solutions and preventative measures such as the RNPC will be crucial if it is to be overcome.

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