Shi-Ying Xuan

Performance of the aspartate aminotransferase‐to‐platelet ratio index for the staging of hepatitis C‐related fibrosis: An updated meta‐analysis

The 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 hepatitis C virus (HCV) monoinfected and HCV / human immunodeficiency virus (HIV) coinfected individuals. 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. 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 coinfected 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 chronic hepatitis C patients. (HEPATOLOGY 2011)

Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis B-related fibrosis: a leading meta-analysis

BackgroundThe 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 systematically review the performance of the APRI in predicting significant fibrosis and cirrhosis in hepatitis B-related fibrosis.MethodsAreas under summary receiver operating characteristic curves (AUROC), sensitivity and specificity were used to examine the accuracy of the APRI for the diagnosis of hepatitis B-related significant fibrosis and cirrhosis. Heterogeneity was explored using meta-regression.ResultsNine studies were included in this meta-analysis (n = 1,798). Prevalence of significant fibrosis and cirrhosis were 53.1% and 13.5%, respectively. The summary AUCs of the APRI for significant fibrosis and cirrhosis were 0.79 and 0.75, respectively. For significant fibrosis, an APRI threshold of 0.5 was 84% sensitive and 41% specific. At the cutoff of 1.5, the summary sensitivity and specificity were 49% and 84%, respectively. For cirrhosis, an APRI threshold of 1.0-1.5 was 54% sensitive and 78% specific. At the cutoff of 2.0, the summary sensitivity and specificity were 28% and 87%, respectively. Meta-regression analysis indicated that the APRI accuracy for both significant fibrosis and cirrhosis was affected by histological classification systems, but not influenced by the interval between Biopsy & APRI or blind biopsy.ConclusionOur meta-analysis suggests that APRI show limited value in identifying hepatitis B-related significant fibrosis and cirrhosis.

Association between HLA-DRB1 alleles polymorphism and hepatocellular carcinoma: a meta-analysis.

BackgroundHLA-DRB1 allele polymorphisms have been reported to be associated with hepatocellular carcinoma susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to explore whether specific HLA-DRB1 alleles (DRB1*07, DRB1*12, DRB1*15) confer susceptibility to hepatocellular carcinoma.MethodsCase-control studies on HLA-DRB1 alleles association with HCC were searched up to January 2010 through a systematic review of the literature. The odds ratios (ORs) of HLA-DRB1 allele distributions in patients with hepatocellular carcinoma were analyzed against healthy controls. The meta-analysis software REVMAN 5.0 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity.ResultsEight case-control studies were included in the final analysis. Among the 3 HLA-DRB1 alleles studied, DRB1*07 and DRB1*12 were significantly associated with the risk of HCC in the whole populations (OR = 1.65, 95% CI: 1.08-2.51, P = 0.02 and OR = 1.59, 95% CI: 1.09-2.32, P = 0.02, respectively). No significant association was established for DRB1*15 allele with HCC in the whole populations. Subgroup analysis by ethnicity showed that DRB1*07, DRB1*12 and DRB1*15 alleles significantly increased the risk of hepatocellular carcinoma in Asians (OR = 2.10, 95% CI: 1.06-4.14, P = 0.03; OR = 1.73, 95% CI: 1.17-2.57, P = 0.006 and OR= 2.88, 95%CI: 1 .77-4.69, P < 0.001 , respectively).ConclusionThese results support the hypothesis that specific HLA-DRB1 alleles might influence the susceptibility of hepatocellular carcinoma. Large, multi-ethnic confirmatory and well designed studies are needed to determine the host genetic determinants of hepatocellular carcinoma.

Lack of association between apolipoprotein C3 gene polymorphisms and risk of nonalcoholic fatty liver disease in a Chinese Han population.

AIM To investigate the association between two polymorphisms of apolipoprotein C3 (APOC3) and risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese Han population. METHODS Genotypes for rs2854116 and rs2854117 in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) in 390 patients with NAFLD and 409 control subjects were determined by sequencing and polymerase chain reaction analysis. Serum lipid profiles were determined using biochemical methods, and an index of insulin resistance (IR, HOMA-IR), serum APOC3 concentrations and total antioxidant status (TAS) were also assessed. RESULTS No significant differences in genotype and allele frequencies of rs2854116 and rs2854117 were found between the NAFLD population and the controls (P > 0.05). The OR for the association between -455C and -482T allele carriers and the risk of NAFLD were 1.06 (95%CI: 0.72-1.57, P > 0.05) and 1.00 (95%CI: 0.68-1.48, P > 0.05), respectively. The variant carriers did not have a significantly increased risk of NAFLD or elevated clinical and biochemical parameters such as APOC3 concentrations, IR (1.42 ± 0.43 vs 1.48 ± 0.52, P > 0.05), liver enzymes and TAS (13.94 ± 2.01 vs 14.38 ± 1.92, P > 0.05) compared with the controls. Moreover, the results were similar when testing was carried out independent of the genetic variation in PNPLA3. CONCLUSION The two polymorphisms of the APOC3 gene are not associated with a risk of NAFLD, or with lipid profiles, IR and oxidative stress in the Chinese Han population.

Specific HLA-DQB1 alleles associated with risk for development of hepatocellular carcinoma: A meta-analysis

AIM To evaluate the association of human leukocyte antigen (HLA)-DQB1 alleles with hepatocellular carcinoma (HCC) through meta-analysis of published data. METHODS Case-control studies on HLA-DQB1 allele association with HCC published up to January 2010 were included in the analyses. The odds ratios (ORs) of HLA-DQB1 allele distributions in HCC patients were analyzed and compared with healthy controls. The meta-analysis software REVMAN 5.0 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. A meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. Seven case-control studies containing 398 cases and 594 controls were included in the final analysis. RESULTS Among the five family alleles, two (DQB1*02 and DQB1*03) were found to be significantly associated with the risk of HCC. The combined OR for the association of DQB1*02 and DQB1*03 allele with the risk for HCC was 1.78 (95% CI: 1.05-3.03, P = 0.03) and 0.65 (95% CI: 0.48-0.89, P = 0.007), respectively. Among the 13 specific alleles, two (DQB1*0502 and DQB1*0602) were significantly associated with risk of HCC. The combined OR for the association of DQB1*0502 and DQB1*0602 allele with the risk for HCC was 1.82 (95% CI: 1.14-2.92, P = 0.01) and 0.58 (95% CI: 0.36-0.95, P = 0.03), respectively. No significant association was established for other HLA-DQB1 family alleles and specific alleles. CONCLUSION Our results support the hypothesis that specific HLA-DQB1 allele families and alleles might influence the susceptibility or resistance to HCC, although it needs further investigations.

Molecular dynamics simulation of PNPLA3 I148M polymorphism reveals reduced substrate access to the catalytic cavity

A missense mutation I148M in PNPLA3 (patatin‐like phospholipase domain‐containing 3 protein) is significantly correlated with nonalcoholic fatty liver disease (NAFLD). To glean insights into mutations effect on enzymatic activity, we performed molecular dynamics simulation and flexible docking studies. Our data show that the size of the substrate‐access entry site is significantly reduced in mutants, which limits the access of palmitic acid to the catalytic dyad. Besides, the binding free energy calculations suggest low affinity for substrate to mutant enzyme. The substrate‐bound system simulations reveal that the spatial arrangement of palmitic acid is distinct in wild‐type from that in mutant. The substrate recognition specificity is lost due to the loop where the I148M mutation was located. Our results provide strong evidence for the mechanism by which I148M affects the enzyme activity and suggest that mediating the dynamics may offer a potential avenue for NAFLD. Proteins 2013.

Relatedness of Helicobacter pylori populations to gastric carcinogenesis.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrica1, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and possibly result from geographical separation of the bacterium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different populations of H. pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H. pylori. Further studies are indicated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals.

PNPLA3 I148M variant in nonalcoholic fatty liver disease: Demographic and ethnic characteristics and the role of the variant in nonalcoholic fatty liver fibrosis

Patatin-like phospholipase domain-containing 3 (PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism, and has been reported to be significantly associated with liver fat content. Various studies have established a strong link between the 148 isoleucine to methionine protein variant (I148M) of PNPLA3 and liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, detailed demographic and ethnic characteristics of the I148M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated. The present review summarizes the current knowledge on the association between the PNPLA3 I148M variant and NAFLD, and especially its role in the development of nonalcoholic fatty liver fibrosis. First, we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148M variant and the presence of metabolic syndrome on the association between PNPLA3 I148M and NAFLD. Then, we explore the role of the PNPLA3 I148M in the development of nonalcoholic fatty liver fibrosis, and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network. Finally, we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148M variant in fibrogenesis, which, in turn, provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.

Reduced genome size of Helicobacter pylori originating from East Asia

Helicobacter pylori (H. pylori), a major pathogen colonizing the human stomach, shows great genetic variation. Comparative analysis of strains from different H. pylori populations revealed that the genome size of strains from East Asia decreased to 1.60 Mbp, which is significantly smaller than that from Europe or Africa. In parallel with the genome reduction, the number of protein coding genes was decreased, and the guanine-cytosine content was lowered to 38.9%. Elimination of non-essential genes by mutations is likely to be a major cause of the genome reduction. Bacteria with a small genome cost less energy. Thus, H. pylori strains from East Asia may have proliferation and growth advantages over those from Western countries. This could result in enhanced capacity of bacterial spreading. Therefore, the reduced genome size potentially contributes to the high prevalence of H. pylori in East Asia.