Background & Aims Hepatitis C virus (HCV) infection has hepatic and extrahepatic manifestations with various costs and impairments to health-related quality of life (HRQL). We performed a ...meta-analysis to determine the prevalence of extrahepatic manifestations in patients with HCV infection, how these impair HRQL, and their costs. Methods We performed systematic reviews of the literature using MEDLINE, CINAHL, and the Cochrane Systematic Review Database, from 1996 through December 2014, to identify studies of the following extrahepatic manifestations of HCV infection: mixed cryoglobulinemia, chronic kidney or end-stage renal disease, type 2 diabetes, B-cell lymphoma, lichen planus, Sjögren’s syndrome, porphyria cutanea tarda, rheumatoid-like arthritis, or depression. We performed a separate meta-analysis for each condition to determine prevalence rates of extrahepatic manifestations of HCV infection and their effects on HRQL. We determined the annual costs (inpatient, outpatient, and pharmacy) associated with extrahepatic manifestations of HCV infection. Results In an analysis of data from 102 studies, we found the most common extrahepatic manifestations to be diabetes (in 15% of patients) and depression (in 25% of patients). HRQL data showed that HCV infection had negative effects on overall physical and mental health. Total direct medical costs of extrahepatic manifestations of HCV infection, in 2014 US dollars, were estimated to be $1506 million (range, $922 million–$2208 million in sensitivity analysis). Conclusions In a systematic review and meta-analysis we determined the prevalence, risks, and costs associated with extrahepatic manifestations of HCV infection. These estimates should be added to the liver-related burden of disease to obtain a more accurate assessment of the total burden of chronic HCV infection. Prospective, real-world studies are needed to increase our understanding of the total clinical and economic effects of HCV infection and treatment on patients and society.
Given significant advances in treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of liver diseases in the USA may be changing. Our aim was to assess ...the shift in the prevalence of different liver disease aetiologies in the USA over the past three decades.
National Health and Nutrition Examination Surveys (NHANES; cross-sectional 1988-1994 and 1999-2016) were used.
A total of 58 731 adults from NHANES (1988-2016) were included. Over the study period, the prevalence of chronic hepatitis B and alcoholic liver disease remained stable: 0.3%-0.4% and 0.8%-1.0%, respectively (p>0.05). The prevalence of chronic hepatitis C decreased nearly twofold: 1.6% in 1988-1994 to 0.9% in 2013-2016 (p=0.03). In contrast, the prevalence of non-alcoholic fatty liver disease (NAFLD; by US-Fatty Liver Index) increased from 20.0% (1988-1994) to 28.3% (1999-2004) to 33.2% (2009-2012) and 31.9% (2013-2016) (p<0.0001). Furthermore, steady increases were observed in the rates of obesity (22.2% in 1988-1994 to 31.0% in 1999-2004 to 38.9% in 2013-2016), type 2 diabetes mellitus (T2DM) (from 7.2% to 8.2% to 13.5% same years), insulin resistance and hypertension (all p<0.0001). Yearly trend analyses showed that the only LD with consistently increasing prevalence was NAFLD (trend p=0.01). Multivariable regression analysis showed that obesity (OR 10.4; 95% CI 9.5 to 11.3) and T2DM (OR 3.7; 95% CI 3.2 to 4.2) were the major independent predictors of NAFLD.
Over the past 30 years in the USA, NAFLD is the only liver disease with growing prevalence, synchronous with the increasing rates of obesity and T2DM.
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady‐state prevalence model to ...quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incidence and remission rates were calculated by calibrating against real‐world prevalence rates. The data were validated using a computerized disease model called DisMod II. NAFLD patients transitioned between nine health states (nonalcoholic fatty liver, nonalcoholic steatohepatitis NASH, NASH‐fibrosis, NASH‐compensated cirrhosis, NASH‐decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, post‐liver transplant, and death). Transition probabilities were sourced from the literature and calibrated against real‐world data. Utilities were obtained from NAFLD patients using the Short Form‐6D. Costs were sourced from the literature and local fee schedules. In the United States, over 64 million people are projected to have NAFLD, with annual direct medical costs of about $103 billion ($1,613 per patient). In the Europe‐4 countries (Germany, France, Italy, and United Kingdom), there are ∼52 million people with NAFLD with an annual cost of about €35 billion (from €354 to €1,163 per patient). Costs are highest in patients aged 45‐65. The burden is significantly higher when societal costs are included. Conclusion: The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577‐1586)
Background & Aims Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs) have common metabolic risk factors. Despite reports from clinical studies, the association between NAFLD, ...cardiovascular disease, and cardiovascular mortality are not clear at the population level. Methods We analyzed data from the National Health and Nutrition Examination Survey III, conducted from 1988 to 1994, and compared hepatic ultrasound and mortality data. Participants were classified into those with NAFLD (moderate or severe hepatic steatosis, based on ultrasound analysis, without any evidence of other liver disease; n = 2492) and those without (absence of NAFLD or any other chronic liver diseases: controls). The prevalence of CVD was compared between subjects with and without NAFLD. Additional comparisons were made between NAFLD patients who had increased levels of liver enzymes and those who had normal levels. Independent predictors of CVD and cardiovascular mortality also were studied. Results During the follow-up period (median, 171 mo), 12.21% of the National Health and Nutrition Examination Survey III participants died; cardiovascular mortality was 3.76%. Regardless of whether levels of liver enzymes were increased or not, individuals with NAFLD were older, predominantly male, more likely to be Hispanic, and less likely to be African American than controls. They also had a higher prevalence of all components of metabolic syndrome and CVD. Regardless of levels of liver enzymes, NAFLD was associated independently with CVD, after adjusting for major demographic, clinical, and metabolic confounders (odds ratio, 1.23; 95% confidence interval, 1.04–1.44). The independent association of NAFLD with cardiovascular mortality was not statistically significant. Conclusions NAFLD is associated independently with an increased risk of CVD. However, NAFLD did not increase cardiovascular mortality over a 14-year period.
The present review discusses the theory and application of van't Hoff analysis in chiral chromatography, with main focus on liquid chromatography. The topics considered include the physical meaning ...of van't Hoff equation's parameters, interpretation of thermodynamic data in terms of retention and enantioseparation mechanisms, abnormal behavior of van't Hoff plots, and best practices to avoid biased results.
Background & Aims Chronic liver diseases (CLDs) are major causes of morbidity and mortality worldwide. We assessed changes in the prevalence of different types of CLD in the United States. Methods ...National Health and Nutrition Examination Surveys conducted between 1988 and 2008 were used to estimate changes in the prevalence and predictors of CLDs. Serologic and clinical data were used to establish the diagnoses of CLDs in 39,500 adults. Statistical analyses were conducted with SUDAAN 10.0 (SAS Institute, Inc, Cary, NC). Results The prevalence rates for CLD were 11.78% (1988–1994), 15.66% (1999–2004), and 14.78% (2005–2008). During the same period, the prevalence of hepatitis B virus infection (0.36%, 0.33%, and 0.34%), hepatitis C virus (1.95%, 1.97%, and 1.68%), and alcoholic liver disease (1.38%, 2.21%, and 2.05%) remained generally stable. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD) increased from 5.51% to 9.84% to 11.01%. From 1988 to 1994, NAFLD accounted for 46.8% of CLD cases; from 1994 to 2004 its prevalence increased to 62.84%, and then to 75.1% from 2005 to 2008. During these time periods, steady increases were observed in obesity (21.74%, 30.02%, and 33.22%), visceral obesity (35.18%, 48.16%, and 51.43%), type II diabetes (5.55%, 7.88%, and 9.11%), insulin resistance (23.29%, 32.50%, and 35.00%), and hypertension (22.68%, 33.11%, and 34.08%). A multivariate analysis showed that during all time periods, obesity was an independent predictor of NAFLD. Conclusions National Health and Nutrition Examination Surveys data collected from 1988 to 2008 show that the prevalence of major causes of CLD remained stable, except for NAFLD, which increased steadily, along with the prevalence of metabolic conditions. Given the increasing rates of obesity, NAFLD prevalence is expected to contribute substantially to the burden of CLD in the United States.
The presence of hepatic steatosis in individuals without a known cause of chronic liver disease, including excessive alcohol consumption, is the hallmark of nonalcoholic fatty liver disease (NAFLD). ...Although NAFLD is usually associated with obesity, nonobese patients can also present with NAFLD ("lean NAFLD"). Our objective was to determine factors independently associated with lean NAFLD in the United States population. For this purpose, we used data from National Health and Nutrition Examination Survey III (NHANES III) conducted between 1988 and 1994 with available hepatic ultrasound, clinico-demographic, and laboratory data. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by ultrasound), the absence of excessive alcohol use (>20 g/d in men and 10 g/d in women), hepatitis B surface antigen(-), and hepatitis C antibody(-). Nonalcoholic steatohepatitis (NASH) was defined as having moderate-severe steatosis and elevated aminotransferases in the presence of type 2 diabetes or insulin resistance (IR). Logistic regression was used to identify independent predictors of lean NAFLD. As a result, of the 11,613 participants included in the study, 2185 (18.77% ± 0.76%) had NAFLD; of these, 307 (11.78% ± 1.03%) had NASH. Multivariate analysis showed that lean NAFLD was independently associated with younger age, female sex, and a decreased likelihood of having IR and hypercholesterolemia (p values < 0.05). Additionally, multivariate analysis showed that NASH was independently associated with being Hispanic, having a younger age, and having components of metabolic syndrome such as hypertension (p values < 0.05). Therefore, we conclude that lean individuals with NAFLD have a different clinical profile than overweight-obese individuals with NAFLD. Furthermore, patients with NASH are commonly Hispanic and have components of metabolic syndrome.
Since the initial description of nonalcoholic steatohepatitis (NASH), several sets of pathologic criteria for its diagnosis have been proposed. However, their interprotocol agreement and ability to ...predict long‐term liver‐related mortality (LRM) have not been demonstrated. In this study, we examined patients with biopsy‐proven nonalcoholic fatty liver disease (NAFLD) for whom liver biopsy slides and clinical and mortality data were available. Liver biopsy samples were evaluated for a number of pathologic features and were classified according to the presence or absence of NASH by (1) the original criteria for NAFLD subtypes, (2) the nonalcoholic fatty liver disease activity score (NAS), (3) the Brunt criteria, and (4) the current study's criteria. All NASH diagnostic criteria and individual pathologic features were tested for agreement and for their independent associations with LRM, which were determined with a Cox proportional hazards model. Two hundred fifty‐seven NAFLD patients with complete data were included. The diagnoses of NASH by the original NAFLD subtypes and by the current study's definition of NASH were in almost perfect agreement (κ = 0.896). However, their agreement was moderate with NAS (κ = 0.470 and κ = 0.511, respectively) and only fair to moderate with the Brunt criteria (κ = 0.365 and κ = 0.441, respectively). Furthermore, the agreement of the Brunt criteria with NAS was relatively poor (κ = 0.178). During the follow‐up (median = 146 months), 31% of the patients died (9% were LRM). After we controlled for confounders, a diagnosis of NASH by the original criteria for NAFLD subtypes adjusted hazard ratio = 9.94 (95% confidence interval = 1.28‐77.08) demonstrated the best independent association with LRM. Among the individual pathologic features, advanced fibrosis showed the best independent association with LRM adjusted hazard ratio = 5.68 (95% confidence interval = 1.50‐21.45). Conclusion: The original criteria for NAFLD subtypes and the current study's criteria for NASH were in almost perfect agreement, but their level of agreement with the NAS and Brunt criteria was lower. A diagnosis of NASH by the original criteria for NAFLD subtypes demonstrated the best predictability for LRM in NAFLD patients. (HEPATOLOGY 2011;)
PDF
