Praveen Kumar Conjeevaram Selvakumar

Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey Data

Objectives:Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of manifestations ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), fibrosis and eventually cirrhosis. The prevalence of NAFLD has been shown to be increasing over time; however, the prevalence of NASH cirrhosis and advanced fibrosis over time has not been well studied. Estimate the changes in prevalence of NASH cirrhosis and NAFLD-associated advanced fibrosis among adults in the United States.Methods:National Health and Nutrition Examination Survey (NHANES) data obtained during the periods from 1999–2002 and 2009–2012 were analyzed to estimate the prevalence of NASH cirrhosis and NAFLD-associated advanced fibrosis in subjects aged ≥18 years at the time of enrollment. We excluded patients with viral hepatitis, excessive alcohol consumption, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >500 and patients who were pregnant. Cirrhosis was defined by AST to platelet ratio index (APRI) >2 and abnormal liver function tests. NASH cirrhosis was defined as cirrhosis that presented with at least one of the following: obesity, diabetes, insulin resistance (HOMA-IR≥3), and metabolic syndrome. Advanced fibrosis was defined by using well-established cutoff values for APRI, fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). Population weighted prevalence was calculated separately for two groups to account for complex sampling method of NHANES.Results:A total of 7034 NHANES participants from 1999–2002 and 2009–2012 group were included with mean age of 46.2±0.59 and 47.3±0.51 years, respectively, at the time of screening. The prevalence of NASH cirrhosis was significantly higher in 2009–2012 group (0.178% with an estimated 417,524 American adults with NASH-associated cirrhosis) compared to 1999–2002 group (0.072%); P value<0.05. The prevalence of NAFLD with advanced fibrosis also increased from 0.84 to 1.75% during the same time period (P value<0.001) corresponding to 4,104,871 American adults. During these time periods, there were also significant increases in obesity (29.8 vs. 36.6%), diabetes (8.3 vs. 11.9%), and insulin resistance (34.7 vs. 42.1%); P value <0.005 for all of them.Conclusions:There has been a 2.5-fold and 2-fold increases in the prevalence of NASH cirrhosis and NAFLD-associated advanced fibrosis, respectively, in 2009–2012 compared to 1999–2002. Extrapolation of NHANES data suggests that in 2010, 417,524 in the US had NASH cirrhosis, and 4,104,871 had NAFLD-associated advanced fibrosis. This represents a major disease burden and suggests the need for widespread programs to identify and treat those affected, and public health efforts aimed at controlling the burden of NAFLD and its complications.

Reduced lysosomal acid lipase activity - A potential role in the pathogenesis of non alcoholic fatty liver disease in pediatric patients.

BACKGROUND Within the spectrum of nonalcoholic fatty liver disease (NAFLD), recent evidence suggests that adult patients with nonalcoholic steatohepatitis (NASH) have significantly lower blood lysosomal acid lipase (LAL) activity than those with steatosis. This has not been studied in pediatric patients with NAFLD. AIM Investigate blood LAL activity in pediatric patients with NAFLD and assess its correlation with histological severity. METHODS We collected data on consecutive children with biopsy-proven NAFLD including demographics, anthropometrics, and routine laboratory tests. The histological features were graded according to the NAFLD activity scoring proposed by Kleiner et al. Blood LAL activity was measured prospectively using Lalistat 2. RESULTS A total of 168 children were included for analysis. Mean age was 12.6±8.5 years, 60.1% were males and 52.4% had NASH. Children with significant fibrosis (stage 2-3, n=64) had a significantly lower LAL activity compared to those with mild fibrosis (stage 0-1, n=104). There was no significant difference in LAL activity between children with NASH compared to those without NASH. CONCLUSION Reduced blood LAL activity correlates with severity of liver fibrosis in children with NAFLD indicating a potential role of reduced LAL activity in the pathogenesis of NAFLD-induced fibrosis.

Nonalcoholic Fatty Liver Disease in Children: Hepatic and Extrahepatic Complications

Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the most common form of chronic liver disease in children and adolescents. The histologic spectrum of NAFLD is broad ranging, from the relatively benign form of simple steatosis to the aggressive form of nonalcoholic steatohepatitis, eventually leading to fibrosis and cirrhosis. NAFLD has also been recognized as an independent risk factor for extrahepatic complications, such as cardiovascular disease, type 2 diabetes mellitus, sleep disorders, and osteoporosis. In this review, we discuss both the hepatic and extrahepatic complications of NAFLD in children.

Nonalcoholic Fatty Liver Disease in Children: Not a Small Matter

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased substantially in the past two decades and NAFLD has now become the most common cause of chronic liver disease in children and adolescents. NAFLD is a broad clinicopathologic spectrum ranging from simple steatosis to varying degrees of necroinflammation called nonalcoholic steatohepatitis (NASH), leading to fibrosis and subsequently to cirrhosis. Despite the increasing prevalence and progressive nature of NAFLD even among children, therapy for NAFLD in both adults and children are limited. Weight loss remains the only consistently effective therapy for NAFLD. Pharmacologic options are even more limited in children than in adults with NAFLD. Vitamin E has been shown to be effective in improving histology in children with NASH. Few pharmacologic options such as metformin, probiotics, omega-3 fatty acids, and cysteamine bitartrate have been studied in children, with limited beneficial effects. However, these studies are limited by small sample size and heterogeneity of outcome assessment after treatment. Recent studies show promising results with bariatric surgery with regards to weight loss and improvement in liver histology in adolescents with NAFLD. In this review article, we discuss epidemiology, pathophysiology, and extrahepatic comorbidities of pediatric NAFLD and review existing therapeutic options for children with NAFLD. We also review novel therapeutic strategies studied in adults that could potentially be studied in children in the future.

The search for noninvasive methods to identify liver fibrosis in children with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the obesity epidemic. Recent studies have clearly shown that the stage of fibrosis in adults with NAFLD is the most important histological feature in long-term outcomes and the development of liver-related complications. Despite the paucity of data regarding the natural history of pediatric NAFLD, its progression to cirrhosis and end-stage liver disease requiring liver transplantation is well documented. Given the high prevalence of NAFLD in children and adults, there is an urgent need to find safe and cost-effective alternatives to biopsy to determine the stage of liver fibrosis. In this review, we provide a concise overview of different noninvasive methods for diagnosing and staging liver fibrosis in children with NAFLD.

Response to Pellicano

2. Saracco GM , Evangelista A , Fagoonee S et al. Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014 . World J Gastroenterol 2016 ; 22 : 8187 – 93 . 3. Ness E , Kowdley KV . Update on hepatitis C: epidemiology, treatment and resistance to antiviral therapies . Minerva Gastroenterol Dietol 2015 ; 61 : 145 – 58 . 4. Doycheva I , Watt KD , Rifai G et al. Increasing burden of chronic liver disease among adolescents and young adults in the USA: A silent epidemic . Dig Dis Sci published online 13 February 2017 .

Survival outcomes scores (SOFT, BAR, and Pedi-SOFT) are accurate in predicting post-liver transplant survival in adolescents.

SOFT and BAR scores utilize recipient, donor, and graft factors to predict the 3‐month survival after LT in adults (≥18 years). Recently, Pedi‐SOFT score was developed to predict 3‐month survival after LT in young children (≤12 years). These scoring systems have not been studied in adolescent patients (13–17 years). We evaluated the accuracy of these scoring systems in predicting the 3‐month post‐LT survival in adolescents through a retrospective analysis of data from UNOS of patients aged 13–17 years who received LT between 03/01/2002 and 12/31/2012. Recipients of combined organ transplants, donation after cardiac death, or living donor graft were excluded. A total of 711 adolescent LT recipients were included with a mean age of 15.2±1.4 years. A total of 100 patients died post‐LT including 33 within 3 months. SOFT, BAR, and Pedi‐SOFT scores were all found to be good predictors of 3‐month post‐transplant survival outcome with areas under the ROC curve of 0.81, 0.80, and 0.81, respectively. All three scores provided good accuracy for predicting 3‐month survival post‐LT in adolescents and may help clinical decision making to optimize survival rate and organ utilization.