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Genetic Pedigree Investigation of Nonalcoholic Fatty Liver Disease

Author: LinZhongHua
Tutor: XuanShiYing
School: Qingdao University
Course: Clinical medicine within science
Keywords: Nonalcoholic fatty liver disease Pedigree investigation Heritability Live fibrosis Noninvasive diagnosis Sensitivity Specificity
CLC: R575.5
Type: Master's thesis
Year: 2011
Downloads: 9
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Abstract

Objective Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease of adults and children in the developed countries. The etiology is believed to be multifactorial with a substantial genetic component; however, the heritability of NAFLD is undetermined. Therefore, a familial aggregation study was performed to test the hypothesis that NAFLD is highly heritable.Method 70 individuals with NAFLD and 30 individuals without NAFLD were chose to serve as probands. Family members were studied, including the first degree relatives、second degree relatives and spouse. Etiologies for fatty liver other than NAFLD were excluded. The method of Falconer was used to estimate the heritability.Results NAFLD was present in 30.4% of the first degree relatives and 10.0% of the second degree relatives of the proband without NAFLD. NAFLD was significantly more common in the first degree relatives (54.3%) and the second degree relatives (13.3%) of the proband with NAFLD. The heritability of the first and second degree relatives were 63.3±10.2% and 34.9±0.8%, respectively.Conclusion These data suggest that familial factors are a major determinant of whether an individual has NAFLD. Genetic factor plays important role in NAFLD. Objective Aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to update the 2007 meta-analysis to systematically assess the accuracy of APRI in predicting significant fibrosis, severe fibrosis and cirrhosis stage in HCV mono-infected and HCV/HIV co-infected individuals.Method Studies comparing APRI versus biopsy in HCV patients were identified via a thorough literature search. Areas under summary receiver operating characteristic curves (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to examine the APRI accuracy for the diagnosis of significant fibrosis, severe fibrosis and cirrhosis. Heterogeneity was explored using meta-regression.Results Twenty one additional studies were eligible for the update and, in total,40 studies were included in this review (n=8,739). The summary AUROC of the APRI for the diagnosis of significant fibrosis, severe fibrosis and cirrhosis were 0.77,0.80 and 0.83, respectively. For significant fibrosis, an APRI threshold of 0.7 was 77% sensitive and 72% specific. For severe fibrosis, a threshold of 1.0 was 61% sensitive and 64% specific. For cirrhosis, a threshold of 1.0 was 76% sensitive and 72% specific. Moreover, we found that the APRI was less accurate for the identification of significant fibrosis, severe fibrosis and cirrhosis in HIV/HCV co-infected patients.Conclusion Our large meta-analysis suggests that APRI can identify hepatitis C-related fibrosis with a moderate degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.

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