Engaging in mild physical active may lower the risk of liver-related mortality, researchers said here. Across two 26-year prospective studies, patients with the highest quintile of physical activity had a 51% lower risk of dying from liver disease compared with sedentary adults after adjusting for age, BMI, diabetes, and hypertension, among other factors (hazard ratio 0.49, 95% CI 0.34-0.70, P<0.0001), reported Tracey Simon, MD, of Massachusetts General Hospital, at the annual Digestive Disease Week. Simon also said the magnitude of risk reduction was similar between participants who exercised vigorously (HR 0.46, 95% CI 0.30-0.69, P=0.0001), which was defined as ≥6 metabolic equivalent tasks (METs) per week, and moderately, defined as 3-6 METs/week (HR 0.57, 95% CI 0.40-0.79, P=0.0003). Individuals who walked a minimum of 4 hours/week had >40% reduced risk versus sedentary adults, which is particularly notable because >85% of those involved in the study reported walking as their primary form of exercise, Simon said. The greatest benefit was seen in patients who walked at least 4 hours/week and used strength training (HR 0.22, 95% CI 0.11-0.40), which "might be related to preventing frailty in this population because that is a huge risk factor for liver-related death," Simon said. "We have for a long time suspected -- and there's evidence to support the notion -- that physical inactivity and obesity increase the risk of liver disease progression, the development of liver cancer, and both all cause and liver-specific mortality," Simon told MedPage Today. "There have been several short-term clinical studies, and a few small randomized clinical trials, showing short-term exercise interventions can improve liver histology, so we all kind of extrapolate to assume that will translate to a survival benefit, but there wasn't any data to support that hypothesis," she said. Obesity has been shown to increase the risk for elevated liver enzymes and has been linked with certain forms of liver disease. Insulin resistance can also lead to the pathologic accumulation of lipids in the liver and is associated with cirrhosis. But because individuals in this study showed similar benefits from physical activity across all levels of BMI, Simon said the association observed in this study didn't seem to be related to excess body weight. Instead, she hypothesized that exercise was affecting insulin resistance, muscle mass, or other factors central to obesity. "Exercise preferentially influences other factors, before it leads to weight loss like insulin resistance and visceral adipose tissue (VAT), both of which really accelerate liver fibrosis and disease progression," Simon said. "What we see in short-term exercise interventions is that, depending on the exercise, the first thing to improve is VAT volume before their body weight changes." Simon's group looked at data from 121,706 women (ages 30 to 55) in the Nurses' Health Study (NHS) and 51,529 men (ages 40 to 75) in the Health Professionals Follow-up Study (HPFS). All patients did not have known cirrhosis or viral hepatitis. Participant characteristics were similar across groups, although adults in the higher physical activity quintiles had lower BMIs and were less likely to have diabetes or smoke. From 1986 to 2010, data on weekly physical activity was measured through biannual responses to questionnaires (90% follow-up). Weekly physical activity was measured by the number of MET hours spent in leisure time walking, running, doing aerobics, strength training, or other activities. Incident viral hepatitis or cirrhosis were also reported at 2-year intervals and liver-related mortalities (hepatocellular carcinoma or cirrhosis-related decompensation) were confirmed through health records and death certificates. Overall, the association between higher physical activity levels and liver-related mortality was similar between women (HR 0.50, 95% CI 0.31-0.81) and men (HR 0.41, 95% CI 0.28-0.77, P=0.0004), Simon reported. The type of liver-related mortality also did not significantly differ, with patients in the highest quintile of physical activity dying at similar rates of hepatocellular carcinoma (HR 0.42, 95% CI 0.23-0.77, P=0.0005), and cirrhosis-specific disease (HR 0.41, 95% CI 0.26-0.63, P<0.0001), she added. Lastly, the association persisted in a sensitivity analysis accounting for 10-year latency exposures, which argues against reverse causation, she said. Study limitations included its observational nature and the fact that physical activity levels were self-reported. Also, Simon and colleagues did not have liver histologies, and self-reported viral hepatitis were not confirmed in all cases by a diagnostic test. Finally, the study population was primarily white so the results might not be generalizable. "For these types of diseases, we need huge populations followed for a long time, and because liver disease is silent for so long, it's really challenging to be able to capture all of these parameters carefully," she concluded. "This is one step closer, but there's a lot more to do." Source
