Nonalcoholic Fatty Liver Disease and Fibrosis Progression: The Good, the Bad, and the Unknown (original) (raw)
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Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva, 2018
A prolonged non-alcoholic steatohepatitis (NASH) condition can lead to advanced stages of liver disease and the development of hepatocellular carcinoma. To evaluate analytical, anthropometric and dietary factors associated with the presence of fibrosis as this is the factor that most influences survival and evolution. Seventy-six patients with liver biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) were included. Biopsies were scored considering the NASH criteria of Kleiner. Analytical, anthropometric and dietary (survey) parameters were obtained. NAFLD-FS is a non-invasive fibrosis index and was assessed for each patient. Leptin, adiponectin, resistin and TNF-alpha serum levels were determined. Fifty-six patients were male (73.7%) and the mean age was 44.5 ± 11.3 years of age (19-68). Thirty-nine (51.3%) (F1-F2: 84.6%; F3-4: 15.4%) patients had fibrosis in the liver biopsy. Seventeen females (85%) had fibrosis versus 22 males (39%), which was statistically significant by u...
Pathologic features associated with fibrosis in nonalcoholic fatty liver disease
Human Pathology, 2004
Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopatholologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis. Although steatosis alone seems to be nonprogressive, some patients with NASH can progress. This study focuses on the clinical and pathological characteristics of patients with NAFLD associated with the development of histological fibrosis. Patients with an established diagnosis of nonalcoholic fatty liver were identified through our NAFLD database containing extensive clinical, demographic, and laboratory data. Liver biopsy specimens were read blindly by one hepatopathologist using a 19-item pathological protocol and by another hepatopathologist using a second pathological protocol. Clinical and pathological data were matched to the presence of different types of histological fibrosis. Univariate and multivariate analyses helped determine all of the variables independently associated with histological fibrosis. Of 132 NAFLD patients, 21.2% had advanced fibrosis (septal/bridging fibrosis or well-established cirrhosis). Sinusoidal fibrosis was present in 20.3% of patients, whereas perivenular fibrosis was seen in 17.2%. Ballooning degeneration and Mallory bodies were independently associated with both sinusoidal fibrosis and perivenular fibrosis. Aspartate aminotransferase/alanine aminotransferase ratio and ballooning degeneration were also independently associated with periportal-portal fibrosis. We conclude that the presence of hepatocyte injury in NAFLD is associated with fibrosis. These pathological features can be used to establish the pathological criteria for diagnosis of the progressive form of NAFLD or NASH. HUM PATHOL 35:196-199.
Clinical Gastroenterology and Hepatology, 2019
BACKGROUND & AIMS: In patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is a risk factor for the development of fibrosis. However, fibrosis has been observed in livers of patients without NASH. We aimed to estimate the prevalence of fibrosis in patients without NASH and risk factors for fibrosis. METHODS: We analyzed data from 1738 subjects (44.9% with severe obesity) in a cross-sectional liver biopsy cohort enrolled at referral centers in Italy and Finland. Biopsy specimens were analyzed histologically by a blinded pathologist at each center, and a diagnosis of NASH was made based on steatosis (‡5% of hepatocytes), hepatocellular ballooning, and lobular inflammation. We also collected data on demographic features, metabolic comorbidities, and genetic factors, and performed logistic regression analyses. Findings were validated using data from 118 consecutive patients with NAFLD who underwent sequential liver biopsies at tertiary referral centers in Italy. RESULTS: In the cross-sectional cohort, 132 of 389 patients (33.9%) with significant fibrosis had no NASH and 39 patients (10.0%) had no inflammation. The dissociation between NASH and fibrosis was significantly greater in patients with severe obesity (P < .005). Steatosis, ballooning, and lobular inflammation each were associated independently with significant fibrosis (P < .001); age, adiposity, fasting hyperglycemia, and the PNPLA3 I148M variant also were associated with fibrosis. In patients without, but not in those with NASH, significant fibrosis was associated with steatosis grade and the PNPLA3 I148M variant. In patients without NASH, age, fasting hyperglycemia, ballooning, and inflammation were associated with fibrosis. In the validation cohort, 16 of 47 patients (34.0%) with clinically significant fibrosis did not have NASH at baseline. In patients with fibrosis without baseline NASH, worsening of fibrosis (based on later biopsies) was associated with fasting hyperglycemia and more severe steatosis (P [ .016).
Nonalcoholic Fatty Liver Disease: Time to Take the Bull by the Horns
Euroasian journal of hepato-gastroenterology
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world affecting almost one-fourth of the population. It may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, end-stage liver disease, and liver cancer in the long run. Besides, it may make the natural history in other chronic liver diseases worse too. Furthermore, patients of NAFLD more often suffer from metabolic syndrome, ischemic heart disease, and extrahepatic malignancies than others, leading to a lower overall survival than the general population. Obesity and sedentary lifestyle are among the most important risk factors for NAFLD apart from increasing age, male sex, and certain genetic factors. Due to the rising incidence, possible adverse consequences, and the futile available treatment options, prevention is the key to tackle this health menace. Spreading awareness, adopting a healthy lifestyle with appropriate dietary modifications, regular physical activity are the cornersto...
Journal of Hepatology, 2011
Background & Aims: Increased visceral adiposity is considered the hallmark of the metabolic syndrome, whose hepatic manifestation is nonalcoholic fatty liver disease (NAFLD), although a subset of patients does not have visceral obesity. Our study aimed to compare metabolic alterations and liver damage in patients with NAFLD with and without visceral obesity. Methods: Four hundred and thirty one consecutive patients with liver biopsy-confirmed NAFLD were divided in three groups according to waist circumference, the simplest surrogate marker of visceral obesity. One hundred and thirty three patients (31%) had a waist circumference 694 (males) and 680 cm (females) (group A), 157 (36%) between 94 and 102, and 80 and 88 (B), and the remaining 141 (33%) had values higher than 102 and 88 cm (C). Results: Significant trends for older age, higher prevalence of female gender, lower HDL, higher triglycerides, altered glucose metabolism, hypertension, and metabolic syndrome were observed with increasing visceral adiposity. In contrast, non-alcoholic steatohepatitis (NASH) detected in 55% and 72% of patients with normal and increased waist circumference, respectively, and the presence of fibrosis P2 were not associated with visceral adiposity. Alanine aminotransferase (ALT), ferritin, HOMA-IR >4, and severe steatosis were independently associated with NASH, whereas ferritin and impaired glucose tolerance were associated with fibrosis P2. Conclusions: Patients with normal waist circumference, despite milder metabolic alterations, may have NASH and are at risk of developing fibrosis, suggesting that once NAFLD is present, visceral obesity is not a major determinant of liver damage severity. Ó
Clinical Epidemiology, 2017
Purpose: To identify the characteristics and initial disease severity of patients with nonalcoholic fatty liver disease (NAFLD) and assess incidence and risk factors for disease progression in a retrospective study. Methods: Patients ≥18 years of age without alcoholism or other liver diseases (eg, hepatitis B/C) were selected from Geisinger Health System electronic medical record data from 2004 to 2015. Initial disease stage was stratified into uncomplicated NAFLD, advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and liver transplant using clinical biomarkers, diagnosis, and procedure codes. Disease progression was defined as stage progression or death and analyzed via Kaplan-Meier plots and multistate models. Results: In the NAFLD cohort (N=18,754), 61.5% were women, 39.0% had type 2 diabetes mellitus (T2DM), and the mean body mass index was 38.2±10.2 kg/m 2. At index, 69.9% had uncomplicated NAFLD, 11.7% had advanced fibrosis, and 17.8% had cirrhosis. Of 18,718 patients assessed for progression, 17.3% progressed (11.0% had stage progression, 6.3% died without evidence of stage progression) during follow-up (median=842 days). Among subgroups, 12.3% of those without diabetes mellitus progressed vs 24.7% of those with T2DM. One-year mortality increased from 0.5% in uncomplicated NAFLD to 22.7% in HCC. After liver transplant, mortality decreased to 5.6% per year. Conclusions: In 2.3 years of follow-up, approximately 17% of patients progressed or died without evidence of stage progression. T2DM was associated with approximately twice the risk of disease progression, and mortality risk increased with disease stage. Early diagnosis and monitoring of disease progression, especially in patients with T2DM, is warranted.
Risk Predictors of Advanced Fibrosis in Non-Alcoholic Fatty Liver Disease
Diagnostics
The assessment of fibrosis in chronic liver diseases using non-invasive methods is an important topic in hepatology. The aim of this study is to identify patients with non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis by establishing correlations between biological/ultrasound markers and non-invasively measured liver stiffness. This study enrolled 116 patients with non-alcoholic fatty liver disease, which were evaluated clinically, biologically, and by ultrasound. Liver fibrosis was quantified by measuring liver stiffness by shear wave elastography (SWE). Multiple correlation analysis of predictors of liver fibrosis identified a number of clinical, biological, and ultrasound parameters (BMI, blood glucose, albumin, platelet count, portal vein diameter, bipolar spleen diameter) that are associated with advanced liver fibrosis in patients with non-alcoholic fatty liver disease. The correlations between the degree of liver fibrosis and the risk values of some serolo...