People with fatty liver disease struggle to lose weight

Losing weight may be especially difficult for people with fatty liver disease due to differences in their metabolism. But nonetheless, some can succeed and doing so improves liver health, according to studies presented at the AASLD Liver Meeting last week in Boston.

Non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH), are responsible for a growing proportion of advanced liver disease as obesity rates rise in the global population. The build-up of fat in the liver triggers cell death and inflammation, which over time can lead to fibrosis, cirrhosis, liver cancer and the need for a liver transplant.

Linked to diabetes and insulin resistance, NAFLD/NASH is increasingly recognised as a manifestation of the metabolic syndrome. There are no effective medical therapies for the condition, and management relies on lifestyle changes such as weight loss and exercise. A loss of 5% of body weight or more has been shown to improve steatosis (liver fat accumulation).

"Globally, obesity and NAFLD are an increasing cause of significant morbidity and mortality, with few effective weight loss strategies available," presenting researcher Dr Ann Farrell of St Vincent’s Hospital in Melbourne, Australia, said in an AASLD press release. "As our understanding of the physiology of obesity and weight homeostasis evolves, so too does our approach to the management of weight loss."

Farrell and colleagues conducted a retrospective cohort study of obese individuals attending an outpatient weight management clinic at St Vincent’s Hospital between July 2015 and February 2019.

Among the 211 evaluable people in the cohort, 113 were diagnosed with NAFLD, defined as a fatty liver index (FLI) score of 60 or higher. The index is based on body mass index (BMI), waist circumference and gamma-glutamyl transferase (GGT) and triglyceride levels. People with heavy alcohol consumption or other causes of liver disease were excluded.

The median age was 48 years. Participants with NAFLD were more likely than those without NAFLD to be men (42% versus 22%) and to have type 2 diabetes (43% versus 27%). Those with NAFLD had a higher weight, BMI and waist circumference, higher levels of GGT and ALT liver enzymes and blood glucose as measured by HbAc1, and greater liver stiffness, an indicator of fibrosis. People with NAFLD were less active (18% vs 34 reported exercise), were more likely to have been obese as children (52% vs 33%) and were more likely to have a family history of obesity (88% vs 74%).

Participants were put on a ketogenic very low energy diet (VLED) that contained 800 calories per day for 12 weeks or until at least 5% weight loss was achieved. The diet consisted largely of meal-replacement drinks, though they were allowed one small meal each day to improve acceptability and adherence. The very low carbohydrate diet is intended to induce ketosis – a state in which the body gets most of its energy from fat rather than glucose – which has been found to increase satiety and reduce hunger.

Prior studies have shown that people with type 2 diabetes lose less weight on such a diet, and Farrell's group aimed to determine if this was the case for people with NAFLD as well.

After three months on the diet, 49% of people with NAFLD and 67% of those without NAFLD had managed to achieve at least a 5% weight loss, a significant difference. However, by six months, the rates had risen to 61% and 75%, respectively, and the difference was no longer significant.

People with NAFLD lost less weight than those without. At three months, the overall percentage loss of total body weight was 4.9% in the NAFLD group and 7.6% in the non-NAFLD group. At six months, the respective percentages were 9.0% and 11.3%. However, neither difference was statistically significant.

After adjusting for other factors, an FLI of 60 or higher – that is, a NAFLD diagnosis – was the only predictor of not achieving at least a 5% weight loss.

"We found that a smaller proportion of patients with NAFLD were able to achieve the target 5% loss of total body weight at three months compared to those with a non-diagnostic fatty liver index," Farrell said. "In our further analysis, this difference was no longer evident when the cohort was followed to six months. This suggests that while obese patients with NAFLD can still achieve significant weight loss on a very-low-calorie diet, they may be slower to reach this point."

"Overall, the weight loss achieved through this outpatient-based diet program was significant," she added. "This is a strategy that should be considered in the management of obese patients with NAFLD moving forward."

In a related study, Dr Miguel Malespin of Tampa General Hospital and colleagues looked at weight loss among people receiving standard care in the TARGET-NASH observational cohort study. TARGET-NASH sites include 59 gastrointestinal, hepatology and endocrinology practices across the United States.

The analysis included 2037 overweight or obese people with NAFLD who enrolled between August 2016 and March 2019 and had at least two available weight measurements. Individuals with decompensated cirrhosis or cancer and those who had undergone bariatric surgery or were taking weight loss medications were excluded.

The participants' median age was approximately 55 years, just over half were women, about 70% were white and about 13% were Latino. Roughly a third each were classified as overweight (BMI 25 to 30), class I obesity (BMI 30 to 35) and class II or III obesity (BMI over 35). Nearly half had diabetes, more than 15% had cardiovascular disease and nearly 10% had NAFLD-related liver cirrhosis.

During about 40 months of follow-up, 32% of participants lost weight. Among those who did so, 34% achieved at least a 5% weight loss, 33% lost at least 7% of their body weight and 10% achieved at least a 10% weight loss. In most cases, weight loss or gain was within 20kg. It took a median of 17.6 months to reach a 5% weight loss.

People who had class II or III obesity (compared to overweight or class I obesity), diabetes, cardiovascular disease, osteoarthritis and cirrhosis, and those who used anti-diabetes medications or had a history of opioid use, were more likely to lose weight.

Participants who reached this weight loss goal were more likely to be seen in academic centres compared with community practices. However, those who did and did not lose weight were equally likely to receive lifestyle modification recommendations (56%). Nutritional counselling and exercise recommendations were uncommon, but appeared to be beneficial.

A fifth of participants with initial weight loss regained their weight back to the baseline level or higher during follow-up, but the researchers noted that only a limited number had been followed for more than a year. 

"In a diverse real-world cohort of patients being managed for NAFLD, approximately [one third] of those who were initially overweight or obese achieved some degree of weight loss during follow-up," the researchers summarised. "Among those who did lose weight, 20% had already regained weight back to baseline within a median of 24-31 months. During extended follow-up, approximately [one fourth] of initially overweight patients maintained weight loss of at least 5%."

Although only mentioned in the study abstract, not the full presentation, weight loss appeared to have a beneficial effect on liver health, as those who lost at least 5% of their body weight saw a decline in ALT, an enzyme that indicates liver inflammation.