Association between the presence of H pylori in the liver and hepatocellular carcinoma: A meta-analysis

AIM: To evaluate the arguments for and against the possible roles of H pylori in hepatocellular carcinoma (HCC). METHODS: We performed a systematic review of all relevant studies published in the literature. A total of 103 clinical trials and reports were identified, but only 10 trials qualified under our selection criteria. A meta-analysis was carried out by a biostatistician according to the Cochrane Reviewers’ Handbook recommended by The Cochrane Collaboration.RESULTS: Nine case-control studies and one retrospective cross sectional study were included in the final analysis. Overall the prevalence of H pylori infection was 53.3% (129 of 242) in cases and 10.4% (29 of 280) in controls, and the summary odds ratio for the association of H pylori infection with the risk for HCC (using the fixed-effects model, which accounted for the homogeneity across the 10 studies) was determined to be 13.63 (95% CI, 7.90-23.49).CONCLUSION: Our analysis showed a positive association between H pylori infection and the risk of HCC, with an indication of possible publication bias and possible confounders due to study designs that showed results of less pronounced associations.

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.Variousstudies 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 I148 M 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 I148 M 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 I148 M variant and the presence of metabolic syndrome on the association between PNPLA3 I148 M and NAFLD.Then,we explore the role of the PNPLA3 I148 M 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 I148 M variant in fibrogenesis,which,in turn,provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.

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 rs2854117in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3(PNPLA3)in 390patients 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-455Cand-482T allele carriers and the risk of NAFLD were1.06(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±2.01vs 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 APOC3gene 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 HLADQB1 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.

Endoscopic stenting and concurrent chemoradiotherapy for advanced esophageal cancer:A case-control study

AIM:To evaluate the role of endoscopic stenting with or without concurrent 3-dimensional conformal chemoradiotherapy (3D-CRT) in patients with inoperable esophageal cancer.METHODS:Advanced esophageal cancer patients indicated for esophagectomy received esophageal stents.A part of patients completed 3D-CRT after stenting.Efficacy was assessed by endoscopy and computed tomographic scan before and 4 wk after completion of the treatment.The median survival,3D-CRT toxicity and complications were compared between 3D-CRT and control groups.RESULTS:From 1999 to 2008,99 consecutive patients with T3/T4 disease and unsuitable for esophagectomy were placed with esophageal stents.Sixty-seven patients received 3D-CRT,while 36 patients treated withendoscopic stents alone were recruited as controls.After 3D-CRT treatment,the median tumor volume of 3D-CRT patients were reduced significantly from 43.7 ± 10.2 cm 3 to 28.8 ± 8.5 cm 3 (P < 0.05).The complete and partial response rate was 85.1%,and no response was 14.9%.After 3D-CRT,the incidence rate of T2 and T3 disease evident on CT scan increased to 78.4% while T4 decreased from 66.7% to 21.6% (P < 0.05).3DCRT Karnofsky Performance Status improved in 3D-CRT patients compared with the control group (P=0.031).3D-CRT patients had a longer survival than the control group (251.7 d vs 91.1 d,P < 0.05).And the median half-year survival rate in 3D-CRT group (91%) was higher than in the control group (50%,P < 0.05).The most common toxicity was leukocytopenia in the 3D-CRT group (46.7% vs 18.8%,P=0.008).The control group had a higher rate of restenosis than the 3D-CRT group (81.3% vs 9.0%,P < 0.05).The rate of nephrotoxicity was increased in 3D-CRT as compared with the control group (31.3% vs 15.6%,P < 0.05).CONCLUSION:3D-CRT can improve dysphagia in patients with inoperable esophageal carcinoma.3D-CRT combined with stenting results in better survival as compared with endoscopic stents used alone.

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.

Apolipoprotein A5 gene polymorphisms are associated withnon-alcoholic fatty liver disease

Background： Several studies have reported that apolipoprotein A5 （APOA5） is involved in the development of non-alcoholic fatty liver disease （NAFLD）. However, no research has been performed regardingthe association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore theassociation between APOA5 gene polymorphisms and NAFLD in a Chinese Han population.

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

AIM: To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level.METHODS: The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group).RESULTS: The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (rs = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(rs = 0.38, P = 0.0001). CONCLUSION: The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman’s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation.

Diagnosis and management of arterioportal fistula occurring after percutaneous transhepatic portal vein cannula-assisted TIPS

To the Editor:Transjugularintrahepaticportosystemicshunt(TIPS)isusuallyconsideredthechoiceformanagingcomplicationsofportal hypertensionsuchasrefractoryascites,esophagogastricvariceal bleedingandrecurrentbleedinguncontrolledwithfirstline treatment.Inrecentyears,TIPShasbeensuccessfullyusedto treat Budd-Chiari syndrome, hepatic hydrothorax, and portal vein thrombosis.One of the key steps during TIPS is the portal vein puncture.

TM6SF2 E167K Variant, a Novel Genetic Susceptibility Variant, Contributing to Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease(NAFLD)is one of the most common causes of liver dysfunction worldwide,and its prevalence is highly associated with genetic susceptibility.The transmembrane 6 superfamily member 2(TM6SF2)E167K variant represents a general genetic determinant of hepatic triglyceride content and lobular inflammation,and its presence appears to be directly involved in the pathogenesis and development of NAFLD.Although this variant appears to be a novel powerful modifier in the development of NAFLD,whether it is associated with an increased risk of NAFLD-refated liver fibrosis and hepatocellular carcinoma(HCC)remains to be determined.The aim of this review is to describe the functions of the TM6SF2 E167K variant and its association with NAFLD,with particular emphasis on the underlying mechanisms of its role in the development and progression of NAFLD.Additionally,the links between the TM6SF2 E167K variant and NAFLD-related liver fibrosis and HCC will be discussed.

Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Bioinformatics and the Role of NR6A1 in the Progression of HCC

Background and Aims:Generally acceptable prognostic models for hepatocellular carcinoma(HCC)are not available.This study aimed to establish a prognostic model for HCC by identifying immune-related differentially expressed genes(IR-DEGs)and to investigate the potential role of NR6A1 in the progression of HCC.Methods:Bioinformatics analysis using The Cancer Genome Atlas and ImmPort databases was used to identify IR-DEGs.Lasso Cox regression and multivariate Cox regression analysis were used to establish a prognostic model of HCC.Kaplan-Meier analysis and the receiver operating characteristic(ROC)curves were used to evaluate the performance of the prognostic model,which was further verified in the International Cancer Genome Consortium(ICGC)database.Gene set enrichment analysis was used to explore the potential pathways of NR6A1.Cell counting kit 8,colony formation,wound healing,and Transwell migration assays using Huh7 cells,and tumor formation models in nude mice were conducted.Results:A prognostic model established based on ten identified IR-DEGs including HSPA4,FABP6,MAPT,NDRG1,APLN,IL17D,LHB,SPP1,GLP1R,and NR6A1,effectively predicted the prognosis of HCC patients,was confirmed by the ROC curves and verified in ICGC database.NR6A1 expression was significantly up-regulated in HCC patients,and NR6A1 was significantly associated with a low survival rate.Gene set enrichment analysis showed the enrichment of cell cycle,mTOR,WNT,and ERBB signaling pathways in patients with high NR6A1 expression.NR6A1 promoted cell proliferation,invasiveness,migration,and malignant tumor formation and growth in vitro and in vivo.Conclusions:An effective prognostic model for HCC,based on a novel signature of 10 immune-related genes,was established.NR6A1 was up-regulated in HCC and was associated with a poor prognosis of HCC.NR6A1 promoted cell proliferation,migration,and growth of HCC,most likely through the cell cycle,mTOR,WNT,and ERBB signaling pathways.