Structure and expression of Cded, a novel gene encoding a pH domain, maps to the distal portion of mouse chromosome 2

There is lack of agreement on the pathologic and clinical features required for establishing the diagnosis of the aggressive type of non-alcoholic fatty liver disease (NAFLD).Aim: To systematically evaluate factors which may differentiate aggressive from non-aggressive NAFLD.Design: 1. Patients with a diagnosis of NAFLD [simple steatosis to non-alcoholic steatohepatitis (NASH)] were identified from a pathology database.2. Patients with other types of liver disease, significant alcohol consumption (>60 gm/day in male and > 20 gm/day in women), malignancy and medications associated with fatty liver were excluded.3. Demographic (3 items), clinical (8 item), potential risk factors (7 items) and biochemical (10 items) data were gathered through systematic chart reviews.4. Each liver biopsy specimen was reviewed by one hepatopathologist using a previously developed NAFLD pathologic questionnaire containing 19 pathologic features, commonly seen in patients with NAFLD.These includes extent, location and type of steatosis, presence of lipid granulnma, degree, type and location of inflammation, sinusoidal location of fibrosis, perivenular location of fibrosis, grade of fibrosis, degree and location of hepatocyte necrosis (spotty, periportal, lobular and bridging), acidophilic bodies, vacuolated nuclei, ballooning degeneration and Mallory hyaline. 5.For each liver biopsy, HCV RNA (by solid tissue PCR method) and iron staining was determined to control for possible confounders.6. Death outcomes are being determined by chart reviews, Ohio cancer registry, National Death Index and telephone surveys.7.Each pathologic feature and clinical characteristic was matched to clinical outcomes (i.e.presence of cirrhosis) and death outcomes using logistic regression model.Result: 1. 772 initial liver biopsies were identified 2. After excluding all of the above entities, 161 liver biopsies were available and to date complete clinico-pathologic data is available for 121 patients.3.There were no differences between cirrhotics and non-cirrhotics in terms of demographics, clinical and most of the biochemical parameters.4. Significant predictors of cirrhosis included presence of diabetes, elevated AST, elevated prothrombin time, elevated T.Bili, extent of steatosis, degree of inflammation, sinusoidal fibrosis, perivenular fibrosis, degree of hepatocyte necrosis, periportal location of hepatocyte necrosis, ballooning degeneration, Mallory hyaline, and grade of fibrosis (p-value<0.05). 5. Histologic iron was not associated with an aggressive outcome and cirrhosis.Conclusion: 1. Except for diabetes, most other clinical and biochemical characteristics cannot distinguish between aggressive and non-aggressive fatty liver.2. Hepatic pathology is the most reliable method for predicting cirrhosis in NAFLD and indicates that biopsy is an important prognostic tool in the management of these patients.