The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis.

Background: Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making. Methods: We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods. Results: Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients. Conclusion: The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles. Systematic review registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.

CB2R agonist GW405833 alleviates acute liver failure in mice via inhibiting HIF-1α-mediated reprogramming of glycometabolism and macrophage proliferation.

The inflammatory responses involving infiltration and activation of liver macrophages play a vital role in acute liver failure (ALF). In the liver of ALF mice, cannabinoid receptor 2 (CB2R) is significantly upregulated on macrophages, while CB2R agonist GW405833 (GW) could protect against cell death in acute liver damage. In this study, we investigated the molecular mechanisms underlying the protective effects of GW against ALF in vivo and in vitro from a perspective of macrophage glycometabolism. Mice were pretreated with GW (10 mg/kg, i.p.), then were injected with D-GalN (750 mg/kg, i.p.) and LPS (10 mg/kg, i.p.) to induce ALF. We verified the protective effects of GW pretreatment in ALF mice. Furthermore, GW pretreatment significantly reduced liver macrophage infiltration and M1 polarization, and inhibited the release of inflammatory factors TNF-α and IL-1ß in ALF mice. These protective effects were eliminated by CB2R antagonist SR144528 or in CB2R-/- ALF mice. We used LPS-stimulated RAW264.7 cells as an in vitro M1 macrophage-centered model of inflammatory response, and demonstrated that pretreatment with GW (10 µM) significantly reduced glucose metabolism by inhibiting glycolysis, which inhibited LPS-induced macrophage proliferation and inflammatory cytokines release. We verified these results in a stable CB2R-/- RAW264.7 cell line. Moreover, we found that GW significantly inhibited the expression of hypoxia inducible factor 1α (HIF-1α). Using a stable HIF-1α-/- RAW264.7 cell line, we confirmed that GW reduced the release of inflammatory cytokines from macrophages and inhibited glycolysis by downregulating HIF-1α expression. In conclusion, activation of CB2Rs inhibits the proliferation of hepatic macrophages and release of inflammatory factors in ALF mice through downregulating HIF-1α to inhibit glycolysis.

The Versatile Gasdermin Family: Their Function and Roles in Diseases.

The gasdermin (GSDM) family, a novel group of structure-related proteins, consists of GSDMA, GSDMB, GSDMC, GSDMD, GSDME/DNFA5, and PVJK/GSDMF. GSDMs possess a C-terminal repressor domain, cytotoxic N-terminal domain, and flexible linker domain (except for GSDMF). The GSDM-NT domain can be cleaved and released to form large oligomeric pores in the membrane that facilitate pyroptosis. The emerging roles of GSDMs include the regulation of various physiological and pathological processes, such as cell differentiation, coagulation, inflammation, and tumorigenesis. Here, we introduce the basic structure, activation, and expression patterns of GSDMs, summarize their biological and pathological functions, and explore their regulatory mechanisms in health and disease. This review provides a reference for the development of GSDM-targeted drugs to treat various inflammatory and tissue damage-related conditions.

Study on the relationship between DNA methylation of target CpG sites in peripheral blood and gestational diabetes during early pregnancy.

Genome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case-control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10-15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for the occurrence of GDM. After adjusting for possible confounders, the hypermethylation status of CpG site 68167324 (OR = 3.168, 1.038-9.666) and 24837915 (OR = 5.232, 1.659-16.506) was identified as more strongly associated with GDM; meanwhile, the hypermethylation of CpG site 157130156 (OR = 0.361, 0.135-0.966) and 89438648 (OR = 0.206, 0.065-0.655) might indicate lower risk of GDM. The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester may be associated with GDM pathogenesis, and has potential as a predictor of GDM.

Estimating the generation interval and inferring the latent period of COVID-19 from the contact tracing data.

The coronavirus disease 2019 (COVID-19) emerged by end of 2019, and became a serious public health threat globally in less than half a year. The generation interval and latent period, though both are of importance in understanding the features of COVID-19 transmission, are difficult to observe, and thus they can rarely be learnt from surveillance data empirically. In this study, we develop a likelihood framework to estimate the generation interval and incubation period simultaneously by using the contact tracing data of COVID-19 cases, and infer the pre-symptomatic transmission proportion and latent period thereafter. We estimate the mean of incubation period at 6.8 days (95 %CI: 6.2, 7.5) and SD at 4.1 days (95 %CI: 3.7, 4.8), and the mean of generation interval at 6.7 days (95 %CI: 5.4, 7.6) and SD at 1.8 days (95 %CI: 0.3, 3.8). The basic reproduction number is estimated ranging from 1.9 to 3.6, and there are 49.8 % (95 %CI: 33.3, 71.5) of the secondary COVID-19 infections likely due to pre-symptomatic transmission. Using the best estimates of model parameters, we further infer the mean latent period at 3.3 days (95 %CI: 0.2, 7.9). Our findings highlight the importance of both isolation for symptomatic cases, and for the pre-symptomatic and asymptomatic cases.

Clinical characteristics of Graves' disease associated cholestasis. / Gravesç— ç›¸å ³æ€§èƒ†æ±æ·¤ç§¯ç—‡çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: A variety of causes can lead to cholestasis, however, cholestasis caused by Graves' disease is usually overlooked clinically. Here we analyze the clinical characteristics of Graves' disease associated cholestasis so as to have a better understanding for the disease. METHODS: We retrospectively collected 13 inpatients' data who suffered from the Graves' disease associated cholestasis in the Department of Infectious Disease of Xiangya Hospital from January 2000 to December 2018. The characteristics of the patients' age, gender, liver function, thyroid function, coagulation function, the special cardiac examination, treatment, and follow-up data were analyzed. RESULTS: Thirteen patients, including 10 males and 3 females with the age range from 33 to 55 (median 43) years old presented cholestasis, pruritus, and hypermetabolic symptoms. The levels of total bilirubin (TBIL), direct bilirubin (DBIL), glutamic-pyruvic transferase, glutamic-oxaloacetic transferase, alkaline phosphosphatase, and gamma glutamyl transpeptidase were 170.4-976.7 (median 388.8) µmol/L, 93.2-418.1 (median 199.2) µmol/L, 25.1-182.1 (median 106.4) U/L, 38.2-265.7 (median 59.7) U/L, 105.3-332.0 (median 184.5) U/L, and 20.7-345.1 (median 47.6) U/L, respectively. The levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyrotrophin receptor antibody were 4.1-50.0 (median 21.6) pmol/L, 30.4-100.0 (median 87.9) pmol/L, and 4.2-40 (median 19.8) U/mL, respectively. All patients' coagulation function, heart size, and ejection fraction (EF) value were normal. After anti-thyroid treatment, the levels of FT3, FT4, and TBIL decreased. Through telephone interview, we were able to know that after 6 months of anti-thyroid treatment, the level of FT3, FT4, and TBIL in these patients returned to normal, and the itch symptom disappeared completely. CONCLUSIONS: Graves' disease can cause cholestasis, with the low incidence. The symptoms of cholestasis can be improved or even eradicated with the cure of the Graves' disease. The cholestasis may be idiopathic. For patients with cholestasis and hyperthyroidism, Graves' disease should be considered for differential diagnosis.

Epidemiological Parameters of COVID-19: Case Series Study.

BACKGROUND: The estimates of several key epidemiological parameters of the COVID-19 pandemic are often based on small sample sizes or are inaccurate for various reasons. OBJECTIVE: The aim of this study is to obtain more robust estimates of the incubation period, serial interval, frequency of presymptomatic transmission, and basic reproduction number (R0) of COVID-19 based on a large case series. METHODS: We systematically retrieved and screened 20,658 reports of laboratory-confirmed COVID-19 cases released by the health authorities of China, Japan, and Singapore. In addition, 9942 publications were retrieved from PubMed and China National Knowledge Infrastructure (CNKI) through April 8, 2020. To be eligible, a report had to contain individual data that allowed for accurate estimation of at least one parameter. Widely used models such as gamma distributions were fitted to the data sets and the results with the best-fitting values were presented. RESULTS: In total, 1591 cases were included for the final analysis. The mean incubation period (n=687) and mean serial interval (n=1015 pairs) were estimated to be 7.04 (SD 4.27) days and 6.49 (SD 4.90) days, respectively. In 40 cases (5.82%), the incubation period was longer than 14 days. In 32 infector-infectee pairs (3.15%), infectees' symptom onsets occurred before those of infectors. Presymptomatic transmission occurred in 129 of 296 infector-infectee pairs (43.58%). R0 was estimated to be 1.85 (95% CI 1.37-2.60). CONCLUSIONS: This study provides robust estimates of several epidemiological parameters of COVID-19. The findings support the current practice of 14-day quarantine of persons with potential exposure, but also suggest the need for additional measures. Presymptomatic transmission together with the asymptomatic transmission reported by previous studies highlight the importance of adequate testing, strict quarantine, and social distancing.

Efficacy and safety of direct acting antiviral regimens for hepatitis C virus and human immunodeficiency virus co-infection: systematic review and network meta-analysis.

BACKGROUND AND AIM: Various all-oral direct-acting antiviral (DAA) regimens are being widely used in the treatment of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients; however, the comparative efficacy and safety of different types and combinations of DAAs are not completely clear. There is still a lack of integration of evidence for optimized therapies for HIV/HCV co-infection. METHODS: We conducted a systematic literature search in several databases up to January 1, 2020. All the studies that reported the sustained virologic response (SVR) and adverse events of DAAs in HIV/HCV co-infected patients were included. The Bayesian Markov Chain Monte Carlo method was used for the pooled estimates of network meta-analysis. RESULTS: We identified 33 eligible articles with 7 combinations of all-oral DAAs for the analyses of efficacy and safety. Grazoprevir-elbasvir ± ribavirin (GZR/EBR ± RBV: 95.6%; 95% CrI, 91.7-98.1%), ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (3D ± RBV: 95.3%; 95% CrI, 93.4-96.9%), sofosbuvir-ledipasvir ± ribavirin (SOF/LDV ± RBV: 95.2%; 95% CrI, 93.7-96.6%), and sofosbuvir-daclatasvir ± ribavirin (SOF/DCV ± RBV: 94.8%; 95% CrI, 92.5-96.6%) were the most effective combinations for HIV/HCV co-infected patients, with SVR rates of approximately 94% and above while severe adverse events were rare. However, the SVR rates of sofosbuvir-ribavirin (SOF/RBV) and sofosbuvir-simeprevir ± ribavirin (SOF/SMV ± RBV) both failed to reach 90%, and the incidences of adverse events were higher than 5%. CONCLUSIONS: Efficacy and safety of all-oral DAAs were in prospect for HIV/HCV co-infection patients. GZR/EBR ± RBV was the optimal combination recommended for HIV/HCV co-infected patients based on the excellent treatment effects and insignificant adverse events.

Protective effects of specific cannabinoid receptor 2 agonist GW405833 on concanavalin A-induced acute liver injury in mice.

Cannabinoid receptor 2 (CB2R) is highly expressed in immune cells and plays an important role in regulating immune responses. In the current study, we investigated the effects of GW405833 (GW), a specific CB2R agonist, on acute liver injury induced by concanavalin A (Con A). In animal experiments, acute liver injury was induced in mice by injection of Con A (20 mg/kg, i.v.). The mice were treated with GW (20 mg/kg, i.p., 30 min after Con A injection) or GW plus the selective CB2R antagonist AM630 (2 mg/kg, i.p., 15 min after Con A injection). We found that Con A caused severe acute liver injury evidenced by significantly increased serum aminotransferase levels, massive hepatocyte apoptosis, and necrosis, as well as lymphocyte infiltration in liver tissues. Treatment with GW significantly ameliorated Con A-induced pathological injury in liver tissue, decreased serum aminotransferase levels, and decreased hepatocyte apoptosis. The therapeutic effects of GW were prevented by AM630. In cell experiments, we showed that CB2Rs were highly expressed in Jurkat T cells, but little expression in L02 liver cells. Treatment with GW (10-40 µg/mL) dose-dependently decreased the viability of Jurkat T cells and induced cell apoptosis, which was reversed by AM630. In the coculture of Jurkat T cells with L02 liver cells, GW dose-dependently protected L02 cells from apoptosis induced by Con A (5 µg/mL). The protective effect of GW was reversed by AM630 (1 µg/mL). Our results suggest that GW protects against Con A-induced acute liver injury in mice by inhibiting Jurkat T-cell proliferation through the CB2Rs.

Scoring systems for prediction of mortality in decompensated liver cirrhosis: A meta-analysis of test accuracy.

AIM: To compare the accuracy of the scoring systems Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease score (MELD), MELD-Na, and MELD to Serum Sodium ratio (MESO) to predict the mortality in decompensated liver cirrhosis. METHODS: The PubMed, Web of Science, Cochrane Library, EMBASE, and Ovid databases were systematically searched from inception to September 2018 for relevant articles, and we evaluated the quality of the included studies. The accuracy of scoring systems was analyzed with Stata 12 and MetaDiSc 1.4. RESULTS: Sixteen studies involving 2337 patients were included. The pooled areas under the summary receiver operating characteristic curves (AUROCs) of CTP, MELD, MELD-Na, and MESO to predict mortality were 0.81, 0.78, 0.85, and 0.86, respectively. Within 3 mo, the AUROCs of CTP, MELD, and MELD-Na in predicting mortality were 0.78, 0.76, and 0.89, respectively. The AUROCs of CTP, MELD, and MELD-Na at 3 mo were 0.86, 0.78, and 0.86, respectively. The AUROCs of CTP, MELD, and MELD-Na at 6 mo were 0.91, 0.83, and 0.90, respectively. The AUROCs of CTP, MELD, and MELD-Na at 12 mo were 0.72, 0.75 and 0.84, respectively. In cirrhotic patients with bleeding, the AUROCs of CTP and MELD were 0.76 and 0.88, respectively. CONCLUSION: MESO has the highest AUROC in all assessed scoring systems. Considering the different time points, MELD-Na has good accuracy in predicting the mortality of decompensated liver cirrhosis. Compared to CTP, MELD is better in predicting variceal bleeding.

Diagnosis of Clostridium difficile infection using an UPLC-MS based metabolomics method.

INTRODUCTION: The fecal metabolome of Clostridium difficile (CD) infection is far from being understood, particularly its non-volatile organic compounds. The drawbacks of current tests used to diagnose CD infection hinder their application. OBJECTIVE: The aims of this study were to find new characteristic fecal metabolites of CD infection and develop a metabolomics model for the diagnosis of CD infection. METHODS: Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to characterize the fecal metabolome of CD positive and negative diarrhea and healthy control stool samples. RESULTS: Diarrhea and healthy control samples showed distinct clusters in the principal components analysis score plot, and CD positive group and CD negative group demonstrated clearer separation in a partial least squares discriminate analysis model. The relative abundance of sphingosine, chenodeoxycholic acid, phenylalanine, lysophosphatidylcholine (C16:0), and propylene glycol stearate was higher, and the relative abundance of fatty amide, glycochenodeoxycholic acid, tyrosine, linoleyl carnitine, and sphingomyelin was lower in CD positive diarrhea groups, than in the CD negative group. A linear discriminant analysis model based on capsiamide, dihydrosphingosine, and glycochenodeoxycholic acid was further constructed to identify CD infection in diarrhea. The leave-one-out cross-validation accuracy and area under receiver operating characteristic curve for the training set/external validation set were 90.00/78.57%, and 0.900/0.7917 respectively. CONCLUSIONS: Compared with other hospital-onset diarrhea, CD diarrhea has distinct fecal metabolome characteristics. Our UPLC-MS metabolomics model might be useful tool for diagnosing CD diarrhea.

Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients.

Metformin has garnered more interest as a chemo-preventive agent given the increased liver cancer risk in diabetic patients. This work was undertaken to better understand the effect of metformin use on liver cancer risk in diabetic patients.A comprehensive literature search was performed in PubMed, Embase, BIOSIS Previews, Web of Science, and Cochrane Library through July 30, 2016. Meta-analyses were performed using Stata version 12.0, with odds ratio (ORs) and 95% confidence intervals (CIs) as effect measures.Twenty-three studies were included. Meta-analysis of 19 studies involving 550,882 diabetic subjects suggested that metformin use reduced the ratio of liver cancer by 48% (OR = 0.52; 95% CI, 0.40-0.68) compared with nonusers. The protective effect was validated in all the exploratory subgroup analyses, except that pooled result of post hoc analyses of 2 randomized controlled trials found no significant difference between subjects with metformin and those without, with OR being 0.84 (95% CI, 0.10-6.83). After adjusting for hepatitis B/C virus infection, cirrhosis, obesity, behavioral factors, and time-related bias, the association was stable, pooled OR ranged from 0.42 to 0.75.A protective effect for liver cancer was found in diabetic metformin users. However, more randomized clinical evidence is still needed to verify the results.

Performance of scoring systems to predict mortality of patients with acute-on-chronic liver failure: A systematic review and meta-analysis.

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) has characteristic feature of multisystem organ failure, rapid progression, and low early transplant-free survival. We performed a meta-analysis to determine the accuracy of five scoring systems in predicting mortality of ACLF patients. METHODS: A systematic database search was performed, and retrieved articles were graded according to methodological quality. Collated data was meta-analyzed by hierarchical summarized receiver operating characteristic model and bivariate model to evaluate the diagnostic accuracy of scoring systems. RESULTS: Of 4223 studies identified, 26 studies involving 4732 ACLF patients were included. The model of end-stage liver disease (MELD) score was found to have largest the area under summarized receiver operating characteristic (AUROC) (0.82) compared with other estimated scoring systems, especially for 3-month mortality. MELD serum sodium (MELD-Na) score showed homologous high accuracy, with the AUROC was 0.81. However, meta-analyses of 16 studies showed that Child-Pugh-Turcotte score had least AUROC (0.71). Sequential organ failure assessment (SOFA) score presented moderately lower diagnostic accuracy, with AUROC being 0.73. Moreover, chronic liver failure-SOFA score presented excellent accuracy of prognostication with highest diagnostic odds ratios. CONCLUSION: This review demonstrated that MELD had moderate diagnostic accuracy to predict mortality of ACLF patients. Considering the expectative diagnostic value, chronic liver failure-SOFA could be regarded as a promising replacement of MELD. To improve the predictive power of scoring systems, multicenter prospective studies of large sample sizes with long-term follow-up are needed.

The benefit of statins in chronic hepatitis C patients: a systematic review and meta-analysis.

BACKGROUND AND AIM: Besides regulating lipid metabolism, statins have garnered considerable interest because of their antiviral and antineoplastic properties. The potential benefit of statins using in chronic hepatitis C (CHC) patients is not well described. This meta-analysis was carried out to quantitatively assess the efficacy of statins in improving the therapeutic effect and prognosis of patients with CHC. PATIENTS AND METHODS: We searched electronic databases for relevant studies comparing the course of benefit in CHC patients with statins versus without statins. Risk estimates were pooled to assess the association of statins use with sustained virological response and the prognosis of CHC patients. RESULTS: Twenty-three studies fulfilled the inclusion criteria. Meta-analysis of 16 homogeneous studies showed that the sustained virological response rate increased by 31% [relative risk (RR)=1.31; 95% confidence interval (CI): 1.23-1.39] in 12 791 CHC patients with statins as an adjuvant under the general antiviral therapy compared with those without this adjuvant therapy. Moreover, meta-analysis of seven studies suggested that statins was beneficial on several specific poor outcomes of CHC patients (RR=0.49; 95% CI: 0.42-0.56). CHC patients with statin use were found to be inversely associated with a 55% reduced risk of hepatocellular carcinoma (RR=0.45; 95% CI: 0.36-0.57) and 53% reduced risk of cirrhosis (RR=0.47; 95% CI: 0.33-0.67) as well as 44% reduced risk of mortality (RR=0.56; 95% CI: 0.46-0.69). However, significant heterogeneity and publication bias were present in some of our analyses. CONCLUSION: Beneficial effects of statins use were found in the therapy and the prognosis of CHC patients. Further prospective studies are still needed to confirm these benefits.

Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis.

Metformin has garnered considerable interest as a chemo-preventive and chemo-therapeutic agent given the increased risk of liver cancer among diabetic patients. This work was performed to illustrate the association between metformin use and survival of diabetic liver cancer patients. We conducted a comprehensive literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane Library from inception to 12 May 2016. Meta-analyses were performed using Stata (version 12.0), with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver cancer patients fulfilled the inclusion criteria. Meta-analyses showed that metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83; p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR = 0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to diabetic liver cancer patients. After adjusting for age, etiology, index of tumor severity and treatment of liver cancer, the association between metformin use and better survival of liver cancer patients was stable, pooled HR ranged from 0.47 to 0.57. The results indicated that metformin use improved survival of diabetic liver cancer patients. However, the results should be interpreted with caution given the possibility of residual confounding. Further prospective studies are still needed to confirm the prognostic benefit of metformin use.

Helicobacter pylori infection may increase the risk of progression of chronic hepatitis B disease among the Chinese population: a meta-analysis.

OBJECTIVES: Helicobacter pylori is a bacterium that infects over 50% of the human population worldwide. An increasing number of studies have demonstrated that H. pylori may cause liver diseases, and the underlying relationship between H. pylori infection and chronic hepatitis B has attracted much attention. This study aimed to examine the association between H. pylori infection and the progression of chronic hepatitis B in the Chinese population. METHODS: A search was performed of the PubMed/MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases, as well as the Chinese databases, China National Knowledge Infrastructure and Wanfang Data, for studies published between January 1, 1994 and November 1, 2015. RESULTS: In total, 2977 patients were included in the chronic hepatitis B group, while 1668 participants were included in the healthy control group. The prevalence of H. pylori among patients with chronic hepatitis B was significantly higher than that among those without chronic hepatitis B. The pooled odds ratio was 3.17. In the subgroup analysis, the odds ratio was 4.28 for hepatitis B virus (HBV)-related cirrhosis and 6.02 for hepatocellular carcinoma. CONCLUSION: These results indicate a strong relationship between H. pylori and chronic hepatitis B, particularly during HBV progression.

The Association between Helicobacter pylori Infection and Chronic Hepatitis C: A Meta-Analysis and Trial Sequential Analysis.

Purpose. Helicobacter pylori is a common gastric disease-inducing pathogen. Although an increasing number of recent studies have shown that H. pylori is a risk factor for liver disease, the potential association between H. pylori infection and chronic hepatitis C still remains controversial. The aim of our meta-analysis was to evaluate a potential association between H. pylori infection and chronic hepatitis C. Methods. We searched the PubMed, Embase, CNKI, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases between January 1, 1994, and May 1, 2015. Results. This study included a total of 1449 patients with chronic hepatitis C and 2377 control cases. The prevalence of H. pylori was significantly higher in patients with chronic hepatitis C than in those without chronic hepatitis C. The pooled odds ratio was 2.93. In a subgroup analysis, the odds ratios were 4.48 for hepatitis C virus- (HCV-) related cirrhosis and 5.45 for hepatocellular carcinoma. Conclusion. Our study found a strong association between H. pylori and chronic hepatitis C, particularly during the HCV progression stage; thus, we recommend active screening for H. pylori in patients with chronic hepatitis C.

[A meta-analysis of liver lesions in hepatitis B patients undergoing anti-tuberculosis therapy].

OBJECTIVE: To evaluate the effect of different immune status on the incidence of hepatic lesions in patients with hepatitis B virus (HBV) infection undergoing anti-tuberculosis therapy. METHODS: The PubMed (1966-2013), Embase (1966-2013), Wanfang (1998-2013), Chinese National Knowledge Infrastructure (CNKI; 1997-2013), and Chinese Biomedical (CBMdisc; 1860-2013) literature databases were searched for case-control studies of hepatic lesions in patients undergoing anti-tuberculosis therapy with or without concomitant HBV infection. The HBV patients were divided into subgroups according to hepatitis B e antigen (HBeAg) positivity or negativity, all members of the control group were HBsAg⁻. The data from all 7 studies included in the meta-analysis were extracted and analysed using RevMan5.2 soft-ware. RESULTS: Patients with HBV infection who were undergoing anti-tuberculosis therapy had a higher risk factor than the control patients (OR =5.81, 95% CI =[4.26, 7.39]). The HBV patients with HBeAg positivity who were undergoing anti-tuberculosis therapy had a high risk factor than the HBV patients with HBeAg negativity (OR =2.56, 95% CI=[1.90, 3.44]). CONCLUSION: HBV infection is a risk factor for hepatic lesions when undergoing anti-tuberculosis therapy, and HBeAg-positive status may put a patient at higher risk.

[Prognostic value of procalcitonin, endotoxin and common inflammatory markers combining MELD score in patients with chronic severe hepatitis].

OBJECTIVE: To evaluate the mid-term prognostic value of procalcitonin (PCT), endotoxin and common inflammatory markers combining the model for end-stage liver disease (MELD) score in patients with chronic severe hepatitis. METHODS: A total of 124 chronic severe hepatitis patients were enrolled, who were hospitalized in the Department of Infectious Diseases, Xiangya Hospital, Central South University from May 2011 to December 2011. Indexes of inflammation, liver and kidney function tests and MELD were determined within 24 h after the admission, and blood samples were collected for measurement of endotoxin , procalcitonin (PCT), and C-reactin protein (CRP). The outcome was confirmed after discharge follow-up at the end of the 3rd month. According to the outcome, the 124 patients were divided into a survival group (n=58) and a death group(n=66). RESULTS: 1) Of the 124 patients, 66 died and 58 survived, with statistical difference in age, MELD score, white blood cell (WBC), polymorphonuclear (PMN), CRP and PCT by single factor analysis between the 2 groups(P<0.05). Binary logistic regression analysis indicated that age, MELD scores and PCT were highly correlated with the outcome (OR=1.07, 1.42 and 1.02 respectively, P<0.05), which could be used to predict the 3 month mid-term mortality of chronic severe hepatitis. 2)There was significant correlation between the MELD scores and the mid-term mortality. Age was positively correlated with the MELD score, and Pearson's correlation coefficient was 0.21 (P<0.05). PCT was also positively correlated with the MELD, and Spearman's correlation coefficient was 0.54 (P<0.01). 3)According to the receiver operation characteristic (ROC) curve analysis , the area under the curve (AUC) of MELD score and PCT were 0.91 and 0.77 respectively, higher than those of other indexes (P<0.01). When the MELD score was up to 30.09 or higher, the predicted mortality risk among these tested patients was the highest(82.26%). The mortality risk predicted by PCT combining MELD score and PCT alone was lower than by MELD score alone (75.00%), but the specificity of MELD score combining PCT was 100%, and the positive prediction value was 1.00. CONCLUSION: Endotoxin and common inflammatory markers (WBC, PMN, and CRP) are not reliable indicators to predict the prognosis in patients with chronic-severe hepatitis. MELD score is significantly correlated with the outcome of mid-term chronic severe hepatitis, PCT and age are both positively correlated with the MELD score. PCT and age combining MELD score can be used to predict the 3 month mid-term mortality of chronic severe hepatitis. MELD score has better prognostic value than PCT. MELD score combining PCT can improve the specificity of prediction.