Nonobese Fatty Liver Disease Kim, Donghee; Kim, W Ray
Clinical gastroenterology and hepatology,
04/2017, Volume:
15, Issue:
4
Journal Article
Peer reviewed
Nonalcoholic fatty liver disease (NAFLD) refers to a group of conditions characterized by hepatic steatosis in the absence of significant alcohol consumption. NAFLD is seen commonly in patients with ...metabolic abnormalities associated with obesity, such as type II diabetes, dyslipidemia, and metabolic syndrome. Evidently, however, not all obese subjects develop NAFLD and, more importantly, NAFLD can be found in nonobese individuals. Although NAFLD occurring in nonobese subjects has been reported in children and adults of all ethnicities, it appears to be recognized more frequently in Asians, even when strict ethnicity-specific body mass index criteria are used to define obesity. Studies based on liver biopsies suggest that the prevalence of nonalcoholic steatohepatitis and fibrosis does not differ significantly between nonobese NAFLD and NAFLD in obese patients. Visceral obesity as opposed to general obesity, high fructose and cholesterol intake, and genetic risk factors (eg, palatin-like phospholipase domain-containing 3) may be associated with nonobese NAFLD. In general, nonalcoholic steatohepatitis is associated with increased mortality, primarily from cardiovascular causes, independent of other metabolic factors. Although data regarding the mortality impact of nonobese NAFLD are not as mature, it may be important to identify high-risk nonobese NAFLD patients and manage their metabolic profile. Currently, lifestyle modification to reduce visceral adiposity, including dietary changes and physical activity, remains the standard of care in patients with nonobese NAFLD.
Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are highly prevalent, affecting approximately one-third of the US population. The relationship between NAFLD and MS is complex and ...may be bidirectionally associated. NAFLD is strongly associated with MS, the components of which include abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. NAFLD associated with certain genetic factors such as the PNPLA3 G allele variant is not accompanied by insulin resistance and MS. Lifestyle modification, including diet and physical activity targeting visceral adiposity, remains the standard of care for patients with NAFLD and MS.
The clinical and public health significance of nonalcoholic fatty liver disease (NAFLD) is not well established. We investigated the long‐term effect of NAFLD on mortality. This analysis utilized the ...National Health and Nutrition Examination Survey conducted in 1988‐1994 and subsequent follow‐up data for mortality through December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known liver diseases. The presence and severity of hepatic fibrosis in subjects with NAFLD was determined by the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and FIB‐4 score. Of 11,154 participants, 34.0% had NAFLD—the majority (71.7%) had NFS consistent with lack of significant fibrosis (NFS <−1.455), whereas 3.2% had a score indicative of advanced fibrosis (NFS >0.676). After a median follow‐up of 14.5 years, NAFLD was not associated with higher mortality (age‐ and sex‐adjusted hazard ratio HR: 1.05; 95% confidence interval CI: 0.93‐1.19). In contrast, there was a progressive increase in mortality with advancing fibrosis scores. Compared to subjects without fibrosis, those with a high probability of advanced fibrosis had a 69% increase in mortality (for NFS: HR, 1.69, 95% CI: 1.09‐2.63; for APRI: HR, 1.85, 95% CI: 1.02‐3.37; for FIB‐4: HR, 1.66, 95% CI: 0.98‐2.82) after adjustment for other known predictors of mortality. These increases in mortality were almost entirely from cardiovascular causes (for NFS: HR, 3.46, 95% CI: 1.91‐6.25; for APRI: HR, 2.53, 95% CI: 1.33‐4.83; for FIB‐4: HR, 2.68, 95% CI: 1.44‐4.99). Conclusions: Ultrasonography‐diagnosed NAFLD is not associated with increased mortality. However, advanced fibrosis, as determined by noninvasive fibrosis marker panels, is a significant predictor of mortality, mainly from cardiovascular causes, independent of other known factors. (HEPATOLOGY 2013)
Disease burden is an important indicator of the state of health of a population. It can be measured as the frequency (eg, incidence and prevalence) of a condition or its effects including fatal and ...non-fatal health loss from disease (eg, disability-adjusted life years) as well as the financial costs (eg, direct healthcare costs and indirect healthcare expenditures related to lost income because of premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic liver disease (CLD) causes substantial health and economic burden in the United States, where nearly 2 million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic steatohepatitis has become a leading indication for liver transplantation. In this article, we assemble available data on the burden of CLD in the United States, focusing on nonmalignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma, an important consequence of CLD, is discussed elsewhere.
Direct‐acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed ...trends in liver transplant (LT) wait‐listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait‐listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End‐Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003‐2010), protease inhibitor (PI; 2011‐2013), and direct‐acting antiviral (DAA; 2014‐2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (–17%; P = 0.002) and DAA eras (–24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all). Conclusion: The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804‐812).
Hepatitis B virus (HBV) remains an important cause of acute and chronic liver disease globally and in the United States. An encouraging trend is that the incidence of acute hepatitis B in the United ...States declined as much as 80% between 1987 and 2004, attributable to effective vaccination programs as well as universal precautions in needle use and in healthcare in general. Although encouraging, these decreases in acute infections have not translated into diminished prevalence or burden of chronic HBV infection. The prevalence for HBV in the United States has been estimated to be approximately 0.4%. However, these estimates have been based on surveys conducted in samples in which population groups with high prevalence of HBV infection, namely foreign‐born minorities, were underrepresented. Voluntary screening data indicate prevalence in excess of 15% in some of these groups. Recent immigration trends suggest a substantial increase in the number of Americans with chronic HBV infection. This trend is reflected in the health and economic burden associated with HBV infection. The number of outpatient visits and hospitalizations for a HBV‐related diagnosis increased several‐fold during the 1990s. Similarly, the total charges for hospitalizations have been estimated to have increased from $357 million in 1990 to $1.5 billion in 2003. Most recent data indicate that death and liver transplant waitlist registration for HBV‐related liver disease, which had been increasing, have now reached a plateau or started to decline. This encouraging trend might be attributable to recent advances in treatment for HBV infection; however, to the extent that the number of Americans living with chronic HBV is growing, careful clinical monitoring and continued epidemiologic surveillance remain important. (HEPATOLOGY 2009;49:S28–S34.)
Background & Aims While the gold standard in the assessment of liver fibrosis remains liver biopsy, non-invasive methods have been increasingly used for chronic hepatitis B (CHB). This study aimed to ...evaluate the performance of two commonly used non-invasive scoring systems (aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4)) to predict fibrosis stage in CHB patients. Materials and methods Demographic, histologic and clinical laboratory data from two trials investigating tenofovir disoproxil fumarate in CHB were analyzed. Predicted fibrosis stage, based on established scales and cut-off values for APRI and FIB-4 scores, was compared with Ishak scores obtained from liver biopsy at baseline and at 240 week follow-up. Results In the 575 patients with a baseline liver biopsy, APRI and FIB-4 scores correlated with Ishak stage ( p <0.01); however extensive overlap in the distribution of both scores across Ishak stages prevented accurate determination of fibrosis. The majority (81–89%) of patients with advanced fibrosis or cirrhosis were missed by the scores. Similarly, 71% patients without fibrosis were misclassified as having clinically significant fibrosis. APRI and FIB-4 scores at week 240 tended to be low and underestimate fibrosis stage in the patients with liver biopsies after 240 weeks of therapy. APRI or FIB-4 reduction did not correlate with fibrosis regression after 240 weeks of antiviral therapy. Conclusions APRI and FIB-4 scores are not suitable for use in clinical practice in CHB patients for assessment of hepatic fibrosis according to Ishak stage, especially in gauging improvements in liver fibrosis following therapy.
The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of ...the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data.
All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model.
The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P < .01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P = .02).
MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity.
An updated version of the Model for End-Stage Liver Disease (MELD) affords improved prediction of mortality risk for patients with cirrhosis and corrects the sex disparity.
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