Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease

Abstract

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can lead to hepatic fibrosis and cirrhosis. Portal fibrosis in the absence of NASH, called isolated portal fibrosis (IPF), has received less attention and has not been classified as a spectrum of NAFLD. The aims of this study were to determine the prevalence of IPF in subjects undergoing gastric bypass surgery, to identify biochemical variables associated with IPF, and to assess the metabolic syndrome as defined by the AdultTreatment Panel III criteria. We analyzed liver biopsies from 195 morbidly obese subjects after excluding all other causes of liver disease. The prevalence of fatty liver (FL) only, IPF, and NASH was 30.3%, 33.3%, and 36.4%, respectively. Several biochemical parameters significantly trended across the 3 groups, with IPF falling between FL and NASH. Hyperglycemia was the only metabolic parameter associated with NASH (OR, 5.4; 95% CI, 2.4-12; P < .0001) and IPF (OR, 2.8; 95% CI, 1.2-6.5; P ‫؍‬ .01). Subjects with diabetes had the greatest risk for NASH (OR, 8; 95% CI, 3.3-19.7; P < .0001) and IPF (OR, 4.3; 95% CI, 1.6-11.6; P ‫؍‬ .003). The metabolic syndrome was identified in 78.5% of subjects, and a significant trend for the number of metabolic criteria was observed across the spectrum of FL, IPF, and NASH. In conclusion, a significant subset of morbidly obese individuals has portal fibrosis in the absence of NASH that is associated with glycemic dysregulation. Therefore, IPF should be considered a spectrum of NAFLD that may prelude NASH in morbid obesity. T he prevalence of obesity (body mass index [BMI]Ն30 kg/m 2 ) in the United States. is 31%. 1 Morbid obesity (BMI Ն 40kg/m 2 ), commonly referred to as clinically severe obesity, is increasing at twice the rate of obesity (BMI 30 -39 kg/m 2 ). 2 Therapy for clinically severe obesity includes pharmacotherapy with behavioral counseling or bariatric surgery. To date, bariatric surgery has proven to be the most successful approach. 3 In 1991, the National Institutes of Health published guideline indications for bariatric surgery that included either a BMI Ն40 kg/m 2 or a BMI Ն35 kg/m 2 associated with medical comorbidities such as type 2 diabetes, hypertension, or sleep apnea. 4 Minimally invasive surgery with the laparoscope has significantly improved postoperative morbidity and mortality following Roux-en-Y gastric bypass surgery (RYGBP) and is presently the most common procedure performed for severe obesity. 5

Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease

“…Isolated periportal fibrosis has been identified in a cohort of bariatric surgery patients as a feature of fibrosis progression in NAFLD (11). The incidence of this feature in our cohort is very low, only 5% of all the biopsies evaluated.…”

Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis

“…However, definite diagnosis requires liver biopsy. 2 A number of studies have shown how components of MS may contribute to alanine aminotransferase (ALT) activity, [4][5][6] severe liver steatosis, 7,8 NASH activity, 8,9 fibrosis 8 or isolated portal fibrosis 10 in adults with NAFLD/NASH.…”

947 Shared Genetic Effects Between Hepatic Steatosis and Fibrosis: A Prospective Twin Study

“…(9) We build on the results of these previous studies to show additional heritabilities between hepatic steatosis and fibrosis. Additionally, NAFLD has been shown to be associated with metabolic risk factors, (17)(18)(19)(20) although it is unknown from these studies the relative contributions of genetic versus environmental factors to these associations. While we have previously demonstrated genetic covariance between NAFLD and metabolic risk factors in a prospective twin study design, gamma-glutamyl transferase was used as a marker of hepatic steatosis, and liver fat content was not measured directly.…”

“…If steatosis and fibrosis gene regulation significantly overlaps then it is plausible that improvement in steatosis by common shared mechanistic pathway may eventually trigger improvement in fibrosis in the context of targeting specific nodal points in the mechanistic pathway. Additionally, previous studies have shown NAFLD to be associated with metabolic risk factors including obesity, hypertension, dyslipidemia, and insulin resistance, (17)(18)(19)(20) and there is a genetic component to this association. (21) However, further studies are needed to characterize the genetic association between hepatic steatosis, fibrosis, and individual metabolic risk factors.…”