Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature.

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.)

Background & Aim Histologic analysis of liver biopsies allows for grading and staging of nonalcoholic fatty liver disease (NAFLD). We performed a longitudinal study to investigate the long-term prognostic relevance of histologic features for patients with NAFLD. Methods We performed a retrospective analysis of 619 patients diagnosed with NAFLD from 1975 through 2005 at medical centers in the United States, Europe, and Thailand. Patients underwent laboratory and biopsy analyses, and were examined every 3–12 months after their diagnosis. Outcomes analyzed were overall mortality, liver transplantation, and liver-related events. Cumulative outcomes were compared by log-rank analysis. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (HR). Time at risk was determined from the date of liver biopsy to the date of outcome or last follow-up examination. Results Over a median follow-up of 12.6 years (range 0.3–35.1), 193 of the patients (33.2%) died or underwent liver transplantation. Features of liver biopsies significantly associated with death or liver transplantation included fibrosis stage 1 (HR, 1.88; 95% CI, 1.28, 2.77), stage 2 (HR, 2.89; 95% CI, 1.93, 4.33), stage 3 (HR, 3.76; 95% CI, 2.40, 5.89), and stage 4 (HR, 10.9; 95% CI, 6.06, 19.62) compared with stage 0, as well as age (HR, 1.07; 95% CI, 1.05, 1.08), diabetes (HR, 1.61; 95% CI, 1.13, 2.30), current smoking (HR, 2.62; 95% CI, 1.67, 4.10) and statin use (HR, 0.32; 95% CI, 0.14, 0.70). Twenty-six patients (4.2%) developed liver-related events; fibrosis stage 3 (HR 14.2 [95% CI 3.38, 59.68]) and stage 4 (HR 51.5 [95% CI 9.87, 269.2]) compared to stage 0, were significantly associated with the events. Patients with fibrosis, regardless of steatohepatitis or NAFLD activity score, had shorter survival times than patients without fibrosis. Conclusions In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were independently associated with long-term overall mortality, liver transplantation, and liver-related events.

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Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end‐stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty‐four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty‐seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P = .001), obesity (P = .002), diabetes mellitus (P = .009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P = .03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P = .003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P = .02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P = .09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.

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