Non-alcoholic Fatty Liver Disease on the Rise, Moderate Exercise is a Viable Solution

The annual Digestive Disease Week, sponsored by the American Association for the Study of Liver Diseases, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Society for Surgery of the Alimentary Tract, was held from May 18 to 21 in San Diego. Two studies caught the attention of Today’s Practitioner: 1. on the increasing rates of liver disease and, 2. on a very simple solution to reducing the risk of liver disease. That solution is moderate walking and exercise.


Rates of Nonalcoholic Fatty Liver Disease Rising, Experts Call for Change.

Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD in a real-world study of 18 million patients in four European cohorts.

The risks for cirrhosis and hepatocellular carcinoma (HCC) have increased for patients with a recorded diagnosis of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), according to a study published online May 20 in BMC Medicine.

liver disease Myriam Alexander, Ph.D., from Real World Data at GlaxoSmithKline in Uxbridge, England, and colleagues extracted data from four European primary care databases and followed patients with a recorded diagnosis of NAFLD or NASH for incident cirrhosis or HCC diagnoses. Each NAFLD/NASH patient was matched with up to 100 non-NAFLD patients.

The researchers identified 136,703 patients with coded NAFLD/NASH out of 18,782,281 adults. Patients with coded NAFLD/NASH were more likely than controls to have diabetes, hypertension, and obesity.

“Making an impact on advanced liver disease will need coordinated efforts to identify those with NAFLD, to stage their disease and target those at risk of progression,” the authors write.

Compared with controls, patients had an increased risk for cirrhosis and HCC (hazard ratios, 4.73 and 3.51, respectively). For either outcome, hazard ratios were higher in patients with NASH and for those with high-risk Fib-4 scores. A baseline diagnosis of diabetes was the strongest independent predictor of a diagnosis of HCC or cirrhosis.

Conclusion / Our knowledge of NAFLD/NASH is being based on small, highly selected cohort studies. These have been accurate in telling us the potential scale of the prevalence and progression of disease, but the reality for many in the general population is some way from that.

In order to affect population health and make an impact on the overall health burden of advanced liver disease, we cannot simply rely on introducing effective therapies to the small number of people with established diagnoses.

The current approach to opportunistically investigate those in whom abnormalities in liver tests arise is clearly not working. While better biomarkers are needed that identify those at risk more precisely, the current tools are not being used, leaving many patients unclear as to the stage of their disease and its significance to their health. Therefore, making an impact on advanced liver disease will need coordinated efforts to identify those with NAFLD, to stage their disease and target those at risk of progression.

Source: Myriam Alexander, et al. Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts. BMC Medicine. May 2019; 17:95.

Increased Physical Activity, such as Walking, Significantly Reduces Liver Disease Risk

Tracey G. Simon, M.D., of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues evaluated physical activity in two large prospective studies of over 113,000 U.S. women and men without known liver disease at enrollment. The investigators performed a 26-year follow-up and evaluated risk factors such as diet, exercise, lifestyle, clinical comorbidities, and alcohol use. This study was presented at Digestive Disease Week.

In the U.S., mortality from chronic liver disease is increasing at an alarming rate, in part due to the epidemic of obesity. Whether increased physical activity is beneficial for the prevention of liver-related mortality is unknown. Moreover, the optimal type and intensity of physical activity to reduce mortality from chronic liver disease is undefined.

Methods/ Researchers prospectively followed 68,449 women from the Nurses’ Health Study (NHS)and 48,748 men from the Health Professionals Follow-up Study (HPFS), who have reported weekly time spent on resistance exercise, walking, and individual aerobic activities every two years from 1986 through 2012, using well-validated questionnaires.

All deaths including cause of death were confirmed by review of medical records, death certificates or by next of kin. Cox proportional hazards regression models were used to calculate age- and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for the relationships between baseline and cumulative updated physical activity and cirrhosis-related death.

Results/ Over 26 years of follow-up (2,957,054 person-years), we recorded 269 deaths attributable to cirrhosis (148 women; 121 men). Physical activity was inversely associated with risk for cirrhosis-related death (P for trend=0.004). Compared to adults in the lowest quintile of physical activity, those in the highest quintile had a 73% lower risk for cirrhosis-related death (adjusted HR 0.27, 95% CI 0.14-0.54).

Equivalent energy expenditures from vigorous aerobic activity and from walking resulted in

comparable magnitudes of risk reduction: specifically, the adjusted HRs for 10 metabolic equivalent task (MET) hours of vigorous aerobic activity and walking were 0.68 (95% CI 0.60-0.88) and 0.52 (95% CI0.38-0.69), respectively. A graded reduction in cirrhosis-related death was found with increasing walking MET score (P for trend=0.010). Further, weekly resistance training (vs.none) was also independently associated with reduced risk for liver-related death (adjusted HR 0.47, 95% CI 0.28-0.76).

In joint analyses, active adults engaging in>9 MET-hours/week of walking together with any resistance training had significantly lower risk of death from chronic liver disease, compared to sedentary adults with<3 MET hours/week of walking and no resistance training (adjusted HR 0.38, 95% CI 0.15-0.79). Conclusions: In two prospective, nationwide cohorts of U.S. adults with 26 years of follow-up, physical activity was associated with substantial reductions in cirrhosis-related mortality. Further risk reduction was observed with combined walking and muscle-strengthening exercises. These findings support further research into the optimum dose, type and intensity of physical activity to reduce mortality from chronic liver disease.

“We found that higher levels of physical activity, measured 26 years before any outcome, significantly reduce the risk from dying of chronic liver disease,” Simon said. “Currently, there are no specific guidelines for the optimal type or intensity of exercise to prevent liver-related mortality. This is very important because, in the United States, liver-related mortality is increasing at an alarming rate.”

In this study, the investigators observed a similar magnitude of benefit when they compared moderate and vigorous aerobic activity. Specifically, the investigators found that regular, moderate activity, including walking at an average pace, significantly reduced risk of mortality from chronic liver disease.

“This is important because walking is the most common form of physical activity among American adults, and it is safe and easily adoptable. Our findings show that walking for four or more hours per week may contribute to a 63 percent reduction in risk of liver-related death,” Simon said. “Our findings demonstrate that physical activity is a major modifiable predictor of liver-related mortality, and engaging in weekly walking activity may reduce the risk of liver-related death in later life.”

The next Digestive Disease Week is scheduled for May 2-5, 2010 in Chicago. For more on the Digestive Disease Week conference, click here.