Dietary Risks for Liver Mortality in NAFLD: Global Burden of Disease Data.

Nonalcoholic fatty liver disease (NAFLD) is a common but complex chronic liver disease, driven by environmental and genetic factors. We assessed metabolic and dietary risk factor associations with NAFLD liver mortality using the Global Burden of Disease (GBD) 2017 data. NAFLD liver deaths were calculated (per 100,000) as age-standardized rates (ASRs) from 195 countries and territories (21 GBD regions; 7 GBD superregions). Dietary risks included low intake of fruits, vegetables, legumes, whole grains, nuts/seeds, milk, fiber, calcium, seafood omega-3 fatty acids, and polyunsaturated fatty acids, and high intake of red meat, processed meat, sugar-sweetened beverages, trans fatty acids, and sodium. Metabolic risks included high low-density lipoprotein cholesterol, systolic blood pressure (BP), fasting glucose (FG), body mass index (BMI), as well as low bone mineral density and impaired kidney function (IKF). Socio-demographic index (SDI)-adjusted partial Spearman correlation coefficients and multivariable generalized linear regression models/bidirectional stepwise selection (significance level for entry, 0.2; for stay, 0.05) determined the associations. The ASR for NAFLD liver deaths was 2.3 per 100,000 (2017) and correlated with dietary risk factors (0.131, -0.010-0.267) and metabolic risk factors (SDI-adjusted = 0.225, 95% CI 0.086-0.354). High intake of sugar-sweetened beverages and red meat (0.358, 0.229-0.475; 0.162, 0.022-0.296), and low intake of nuts/seed and milk (0.154, 0.014-0.289; 0.145, 0.004-0.280) was significant for NAFLD liver deaths. Other risk factors for liver death included IKF (0.402, 0.276-0.514), increased BMI (0.353, 0.223-0.407), FG (0.248, 0.111-0.376), and BP (0.163, 0.022-0.297). High intake of trans fatty acids (2.84% increase [1.65%-4.03%]) was the largest associated risk of NAFLD liver deaths. In addition to metabolic risks, dietary risks independently drive the global burden of NAFLD-related liver mortality. Conclusion: These data provide additional support for policies to improve dietary environment for NAFLD burden reduction.

Nonalcoholic fatty liver disease: impact on healthcare resource utilization, liver transplantation and mortality in a large, integrated healthcare system.

BACKGROUND AND AIMS: NAFLD is the most prevalent liver disease globally, affecting 20% of the world population. Healthcare resource utilization (HRU) attributable to NAFLD has been difficult to define. METHODS: We performed a case control study on NAFLD patients from 2005 to 2015 in a large integrated healthcare system with an affiliated insurance company that prospectively captures HRU information. Outcomes encompassed costs, liver transplantation and mortality rates. RESULTS: There were 17,085 patients, of which 4512 were NAFLD cases and 12,573 were non-NAFLD controls. The cohorts were similar in age and gender distribution (p > 0.05). The NAFLD cohort had a younger mean age of death (60.9 vs. 63.3, p = 0.004) and had over twice the number of annual healthcare visits (14.6 vs. 7.1). The increased overall annual overall cost attributable to NAFLD (in 2015 $) was $449/year. Overall, NAFLD was independently associated with 17% higher annual attributable healthcare costs. More advanced NAFLD (FS 3-4) was associated with a 40% increase in median annual healthcare costs (vs. FS 0-2). The strongest predictors of HRU among patients with NAFLD were advanced fibrosis and medical co-morbidities. The rate of liver transplantation was 18 times greater (0.054%/year) in the NAFLD compared with the non-NAFLD cohort, while mortality rate was 1.7 times greater. CONCLUSIONS: Within a large, integrated healthcare system a diagnosis of NAFLD is independently associated with a 17% overall excess in HRU and a several-fold increase liver transplantation and mortality. Although the dollar amounts will change over time and between healthcare systems, the proportional need for HRU will have broad applicability and implications.

Mortality rates among individuals diagnosed with hepatitis C virus (HCV); an observational cohort study, England, 2008 to 2016.

BackgroundMonitoring trends in mortality for individuals diagnosed with hepatitis C virus (HCV) infection are important as we expand treatment and move towards World Health Organization elimination targets.AimTo estimate mortality rates for individuals aged ≥ 15 years diagnosed with HCV infection in England 2008-16.MethodsAn observational cohort study whereby death certificate information was linked to the Sentinel Surveillance of Blood Borne Virus Testing in England. Age-sex standardised mortality rates (ASMR) for individuals diagnosed with HCV infection (2008-16) were calculated and compared to the general population.ResultsOf 43,895 individuals with HCV infection, 2,656 (6.3%) died. All-cause ASMRs were 2,834.2 per 100,000 person years (PY), 2.3 times higher than in the general population. In individuals aged 30-69 years, all-cause mortality rates were 1,768.9 per 100,000 PY among individuals with HCV, 4.7 times higher than in the general population. ASMRs had not decreased between 2010 (2,992) and 2016 (2,340; p=0.10), with no change from 2014 (p = 0.058). ASMRs were 441.0 times higher for hepatitis, 34.4 times higher for liver cancer, 8.1 times higher for end stage liver disease and 6.4 times higher for external causes than in the general population.ConclusionsMortality was higher in individuals with diagnosed HCV infection compared to the general population, highlighting health inequalities. There is a need to improve HCV diagnosis, engagement in care and treatment rates. The high mortality from external causes highlights the importance of integrated health and social care strategies and addressing the needs of this vulnerable population.

Nutritional issues in patients with obesity and cirrhosis.

Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.

Treatment options for alcoholic and non-alcoholic fatty liver disease: A review.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma. Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver (simple steatosis), a small percentage develops progressive liver disease. Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available. The treatment for ALD remains as it was 50 years ago: abstinence, nutritional support and corticosteroids (or pentoxifylline as an alternative if steroids are contraindicated). As for NAFLD, the treatment modality is mainly directed toward weight loss and co-morbidity management. Therefore, new pathophysiology directed therapies are urgently needed. However, the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination therapy towards multiple targets would eventually be required. In this review, we delineate the treatment options in ALD and NAFLD, including various new targeted therapies that are currently under investigation. We hope that soon we will be having an effective multi-therapeutic regimen for each disease.

Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury.

Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers (thiazolidinediones) and antioxidants (vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH.