Sushma Saksena

The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.

Patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis are at the highest risk for progressing to end‐stage liver disease. We constructed and validated a scoring system consisting of routinely measured and readily available clinical and laboratory data to separate NAFLD patients with and without advanced fibrosis. A total of 733 patients with NAFLD confirmed by liver biopsy were divided into 2 groups to construct (n = 480) and validate (n = 253) a scoring system. Routine demographic, clinical, and laboratory variables were analyzed by multivariate modeling to predict presence or absence of advanced fibrosis. Age, hyperglycemia, body mass index, platelet count, albumin, and AST/ALT ratio were independent indicators of advanced liver fibrosis. A scoring system with these 6 variables had an area under the receiver operating characteristic curve of 0.88 and 0.82 in the estimation and validation groups, respectively. By applying the low cutoff score (−1.455), advanced fibrosis could be excluded with high accuracy (negative predictive value of 93% and 88% in the estimation and validation groups, respectively). By applying the high cutoff score (0.676), the presence of advanced fibrosis could be diagnosed with high accuracy (positive predictive value of 90% and 82% in the estimation and validation groups, respectively). By applying this model, a liver biopsy would have been avoided in 549 (75%) of the 733 patients, with correct prediction in 496 (90%). Conclusion: a simple scoring system accurately separates patients with NAFLD with and without advanced fibrosis, rendering liver biopsy for identification of advanced fibrosis unnecessary in a substantial proportion of patients. (HEPATOLOGY 2007;45:846–854.)

Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis

Aims: Factors responsible for the progression of non-alcoholic fatty liver disease (NAFLD) to more severe liver injury are poorly understood. In the present study, we investigated the association between immune reactions triggered by oxidative stress and stage of NAFLD. Methods: Titres of IgG against human serum albumin adducted with malondialdehyde (MDA-HSA) or arachidonic acid hydroperoxide (AAHP) and against oxidised cardiolipin (Ox-CL) were measured in 167 NAFLD patients with steatosis only (n = 79), steatohepatitis (n = 74), or steatosis plus cirrhosis (n = 14), and in 59 age and sex matched controls. Results: Circulating IgG against lipid peroxidation products was significantly higher (p<0.001) in NAFLD patients than in controls. Oxidative stress dependent immune responses were not associated with obesity, type 2 diabetes, or with serum cholesterol, ferritin, or aminotransferase levels. Titres of lipid peroxidation related antibodies were also independent of the extent of steatosis and were similarly distributed in patients with and without necroinflammation. In contrast, the same antibodies were significantly increased in patients with advanced fibrosis or cirrhosis. Logistic regression analysis confirmed that anti-MDA antibodies were independently associated with progression of NALFD and that NAFLD patients with titres of anti-MDA-HSA antibodies above the control threshold value had a threefold (relative risk 2.82 (95% confidence interval 1.35–5.90); p = 0.007) higher risk of having advanced fibrosis/cirrhosis than patients whose antibody titres were within the control range. Conclusions: These results indicate that the presence of immune reactions triggered by oxidative stress can be an independent predictor of progression of NAFLD to advanced fibrosis.

Non-alcoholic steatohepatitis: Definitions and pathogenesis

This description remains appropriate because nonalcoholic fatty liver disease (NAFLD) can range from simple steatosis, through NASH and fibrosis to cirrhosis with fat. 2 In addition to fat, the histological diagnosis of NASH ideally requires evidence of (i) hepatocyte injury, manifest by swollen or ‘ballooned’ cells; (ii) an inflammatory infiltrate, predominantly neutrophils, with or without (iii) fibrosis, typically perivenular/pericellular in distribution. Each of these features can be graded to derive a score recently proposed by Brunt et al. 3 Rigorous exclusion of alcohol as a cause of the histology is, of course required and this is best achieved by a combination of repeated questioning of patients and ideally friends/relatives, frequent random blood alcohol estimations and measurement of mean cell corpuscular volume (MCV). No pattern of liver blood test abnormalities is either specific or sensitive enough to distinguish between NAFLD and alcohol-related liver disease.