Physical deconditioning is the common denominator in both obese and overweight subjects with nonalcoholic steatohepatitis.

BACKGROUND: Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD). AIM: We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects. METHODS: Forty subjects (60% obese, 40% overweight) with biopsy-confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained. RESULTS: NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the "least fit" tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs "least fit" 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs "least fit" 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT. CONCLUSIONS: Aerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's "least fit" untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted.

Review article: prescribing medications in patients with cirrhosis - a practical guide.

BACKGROUND: Most drugs have not been well studied in cirrhosis; recommendations on safe use are based largely on experience and/or expert opinion, with dosing recommendations often based on pharmacokinetic (PK) changes. AIM: To provide a practical approach to prescribing medications for cirrhotic patients. METHODS: An indexed MEDLINE search was conducted using keywords cirrhosis, drug-induced liver injury, pharmacodynamics (PDs), PKs, drug disposition and adverse drug reactions. Unpublished information from the Food and Drug Administration and industry was also reviewed. RESULTS: Most medications have not been adequately studied in cirrhosis, and specific prescribing information is often lacking. Lower doses are generally recommended based on PK changes, but data are limited in terms of correlating PD effects with the degree of liver impairment. Very few drugs have been documented to have their hepatotoxicity potential enhanced by cirrhosis; most of these involve antituberculosis or antiretroviral agents used for HIV or viral hepatitis. Paracetamol can be used safely when prescribed in relatively small doses (2-3 g or less/day) for short durations, and is recommended as first-line treatment of pain. In contrast, NSAIDs should be used cautiously (or not at all) in advanced cirrhosis. Proton pump inhibitors have been linked to an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhosis and should be used with care. CONCLUSIONS: Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended, due to altered PKs. Drugs that can precipitate renal failure, gastrointestinal bleeding, SBP and encephalopathy should be identified and avoided.

Liquid sucrose bingeing in rats depends on the access schedule, concentration and delivery system.

Previous studies have reported binge-type consumption of solid vegetable shortening in non-food deprived rats maintained on schedules of limited shortening access. The current study determined if limited access would promote binge-type consumption of sucrose solutions. Adult male rats (6 groups, n = 10 each) were provided with one of three different sucrose concentrations (3.2%, 10%, 32% w/v) for 2 h either everyday (Daily) or Monday, Wednesday, and Friday (Intermittent). A 'binge' during the 2-h access periods was operationally defined as Intermittent intakes significantly greater than Daily intakes. Sucrose initially was provided in a 100 ml glass tube equipped with a stainless-steel drinking spout. Under these conditions, there were no differences in sucrose intake between Daily and Intermittent groups at any of the concentrations. In contrast, when sucrose was provided in a modified 60 ml plastic syringe with the same drinking spout, intakes of the Intermittent groups consuming 3.2% and 10% sucrose were greater than those of the respective Daily groups, indicating that binge-type consumption of sucrose occurred. These results demonstrate that brief, intermittent access to low and moderate concentrations of sucrose can promote binge-type behavior, and the characteristics of the drinking apparatus can affect sucrose intake.