A low prevalence of H pylori and endoscopic findings in HIV-positive Chinese patients with gastrointestinal symptoms

AIM： To compare the prevalence of H pylori infection, peptic ulcer, cytomegalovirus （CNV） infection and Candida esophagitis in human immunodeficiency virus （HIV）- positive and HIV-negative patients, and evaluate the impact of CD4 lymphocyte on H pylori and opportunistic infections. METHODS： A total of 151 patients （122 HIV-positive and 29 HIV-negative） with gastrointestinal symptoms were examined by upper endoscopy and biopsy. Samples were assessed to determine the prevalence of Hpylori infection, CMV, candida esophagitis and histologic chronic gastritis. RESULTS： The prevalence of Hpylori was less common in HIV-positive patients （22.1%） than in HIV-negative controls （44.8%; P 〈 0.05）, and the prevalence of H pylori displayed a direct correlation with CD4 count stratification in HIV-positive patients. In comparison with HIV-negative group, HIV-positive patients had a lower incidence of peptic ulcer （20.7% vs 4.1%; P 〈 0.01）, but a higher prevalence of chronic atrophy gastritis （6.9% vs 24.6%; P 〈 0.05）, Candida esophagitis and CMV infection. Unlike HIV-negative group, H pylori infection had a close relationship to chronic active gastritis （P 〈 0.05）. In HIV-positive patients, chronic active gastritis was not significantly different between those with Hpylori infection and those without. CONCLUSION： The lower prevalence of H pylori infection and peptic ulcer in HIV-positive patients with gastrointestinal symptoms suggests a different mechanism of peptic ulcerogenesis and a different role of H pylori infection in chronic active gastritis and peptic ulcer. The pathogen of chronic active gastritis in HIV-positive patients may be different from the general population that is closely related to Hpylori infection.

Antiviral drug resistance increases hepatocellular carcinoma:A prospective decompensated cirrhosis cohort study

AIM:To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.METHODS:Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort.With two years of follow-up,198patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.RESULTS:Among the antiviral treatment patients,162had a complete virological response(CVR),and 36 were drug-resistant(DR).The two-year cumulative incidence of hepatocellular carcinoma(HCC)in the DR patients(30.6%)was significantly higher than that in both the CVR patients(4.3%)and the control group(10.3%)(P<0.001).Among the DR patients in particular,the incidence of HCC was 55.6%(5/9)in those who failed rescue therapy,which was extremely high.The rtA181T mutation was closely associated with rescue therapy failure(P=0.006).The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline(8.9±2.3 vs 6.0±1.3,P=0.043).CONCLUSION:This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients,especially in those who failed rescue therapy.

Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients

AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma.

Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma

AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy,Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide,Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.RESULTS: Among the 160 HCC patients enrolled in this study,130 patients survived 2 years (81.25%),with a survival rate of 86.8% in AFP < 2 0 μg/L group,88.9% in AFP 20-250 μg/L group,and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was benef icial only in patients with low AFP levels.The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management.The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP.Consistently,in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth,and this was more apparent in HepG2 cells,in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percent-age of HepG2 cells in S phase after exposure to AFP was modestly increased.CONCLUSION:HCC patients with higher AFP levels show a higher mortality rate,which appears to be attributable to the growth promoting properties of AFP.

Chinese guidelines on management of hepatic encephalopathy in cirrhosis

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists’ consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.

Chinese guidelines on the management of liver cirrhosis(abbreviated version)

Based on reviews of the literature and experts’consensus,the Chinese Society of Hepatology developed guidelines for the diagnosis and treatment of liver cirrhosis,in order to improve clinical practice.In addition to what has been covered in previously published guidelines on the management of cirrhosis complications,these guidelines add new sections and provide updates.The guidelines emphasize the early diagnosis of the cause and assessment of complications.Comprehensive treatments including etiological treatment and complication management should be initiated immediately.In addition,regular monitoring,especially surveillance of hepatocellular carcinoma,is crucial for managing patients.

Computed tomography vs liver stiffness measurement and magnetic resonance imaging in evaluating esophageal varices in cirrhotic patients:A systematic review and meta-analysis

BACKGROUND Computed tomography(CT),liver stiffness measurement(LSM),and magnetic resonance imaging(MRI)are non-invasive diagnostic methods for esophageal varices(EV)and for the prediction of high-bleeding-risk EV(HREV)in cirrhotic patients.However,the clinical use of these methods is controversial.AIM To evaluate the accuracy of LSM,CT,and MRI in diagnosing EV and predicting HREV in cirrhotic patients.METHODS We performed literature searches in multiple databases,including Pub Med,Embase,Cochrane,CNKI,and Wanfang databases,for articles that evaluated the accuracy of LSM,CT,and MRI as candidates for the diagnosis of EV and prediction of HREV in cirrhotic patients.Summary sensitivity and specificity,positive likelihood ratio and negative likelihood ratio,diagnostic odds ratio,and the areas under the summary receiver operating characteristic curves were analyzed.The quality of the articles was assessed using the quality assessment of diagnostic accuracy studies-2 tool.Heterogeneity was examined by Q-statistic test and I2 index,and sources of heterogeneity were explored using metaregression and subgroup analysis.Publication bias was evaluated using Deek’s funnel plot.All statistical analyses were conducted using Stata12.0,Meta Disc1.4,and Rev Man5.3.RESULTS Overall,18,17,and 7 relevant articles on the accuracy of LSM,CT,and MRI in evaluating EV and HREV were retrieved.A significant heterogeneity was observed in all analyses(P<0.05).The areas under the summary receiver operating characteristic curves of LSM,CT,and MRI in diagnosing EV and predicting HREV were 0.86(95%confidence interval[CI]:0.83-0.89),0.91(95%CI:0.88-0.93),and 0.86(95%CI:0.83-0.89),and 0.85(95%CI:0.81-0.88),0.94(95%CI:0.91-0.96),and 0.83(95%CI:0.79-0.86),respectively,with sensitivities of 0.84(95%CI:0.78-0.89),0.91(95%CI:0.87-0.94),and 0.81(95%CI:0.76-0.86),and 0.81(95%CI:0.75-0.86),0.88(95%CI:0.82-0.92),and 0.80(95%CI:0.72-0.86),and specificities of 0.71(95%CI:0.60-0.80),0.75(95%CI:0.68-0.82),and 0.82(95%CI:0.70-0.89),and 0.73(95%CI:0.66-0.80),0.87(95%CI:0.81-0.92),and 0.72(95%CI:0.62-0.80),respectively.The corresponding positive likelihood ratios were 2.91,3.67,and 4.44,and 3.04,6.90,and2.83;the negative likelihood ratios were 0.22,0.12,and 0.23,and 0.26,0.14,and 0.28;the diagnostic odds ratios were 13.01,30.98,and 19.58,and 11.93,49.99,and 10.00.CT scanner is the source of heterogeneity.There was no significant difference in diagnostic threshold effects(P>0.05)or publication bias(P>0.05).CONCLUSION Based on the meta-analysis of observational studies,it is suggested that CT imaging,a non-invasive diagnostic method,is the best choice for the diagnosis of EV and prediction of HREV in cirrhotic patients compared with LSM and MRI.

Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study

BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 wk.The ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after treatment.In addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment.The patients were followed for 6 mo.RESULTS Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics.The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics.CONCLUSION Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites.A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria,thus improving the systemic inflammatory state.

Key role of hepatitis B virus mutation in chronic hepatitis B development to hepatocellular carcinoma

Chronic hepatitis B virus(HBV) infection is a major risk factor for hepatocellular carcinoma(HCC). The HBV mutations, which include point mutation, deletion,insertion and truncation mutation of HBV gene in 4 open reading frames(S, C, P, X), are closely associated with HCC pathogenesis. Some mutations accumulated during chronic HBV infection could be regarded as a biomarker to predict the occurrence of HCC. The detection of the mutations in clinical practice could be helpful for defining better preventive and therapeutic strategies and, moreover, predicting the progression of liver disease.

Helicobacter pylori infection and peptic ulcer disease in cirrhotic patients:An updated meta-analysis

BACKGROUND Peptic ulcer(PU)is more prevalent in patients with liver cirrhosis.The role of Helicobacter pylori(H.pylori)infection in the pathogenesis of PU in patients with cirrhosis is still not elucidated.AIM To perform a meta-analysis on the prevalence of H.pylori infection and PU and their association in liver cirrhosis patients.METHODS We searched PubMed,EMBASE,Web of Science,Cochrane,CNKI,Wangfang,and CQVIP databases from inception to July 10,2020.Odds ratio(OR)and 95%confidence interval(CI)were pooled using a random-effects model.The statistical heterogeneity among studies(I2-index),subgroup analyses,regression analysis,sensitivity analysis,and the possibility of publication bias were assessed.RESULTS A total of 14 studies(13 cross-sectional studies;1 cohort study)involving 2775 individuals(611 cases with PU and 2164 controls)were included in our metaanalysis.The prevalence of PU in patients with cirrhosis was 22%.The prevalence of H.pylori infection was 65.6%in cirrhotic patients with PU,and 52.5%in those without.The pooled overall OR was 1.73(95%CI:1.16-2.56,I2=66.2%,P<0.001,Z=2.7,Pz<0.05).We did not find the cause of heterogeneity in the subgroup analyses and meta-regression analysis except for one study.Funnel plot did not show significant publication bias.The results of Begg’s test and Egger’s test indicated no evidence of substantial publication bias(P_(Begg)=0.732,P_(Egger)=0.557).CONCLUSION There is a weakly positive association between H.pylori infection and PU in patients with liver cirrhosis.It is suggested that H.pylori infection may play a role in the pathogenesis of PU in liver cirrhotic patients.

Can a fibrotic liver afford epithelial-mesenchymal transition?

The question whether epithelial-mesenchymal transition (EMT) occurs during liver fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes or cholangiocytes undergo EMT upon transforming growth factor beta (TGF-beta) stimulation, whereas in vivo experiments based on genetic fate mapping of specific cell populations suggest that EMT does not occur in fibrotic animal models. In this review we present current data supporting or opposing EMT in chronic liver disease and discuss conditions for the occurrence of EMT in patients. Based on the available data and our clinical observations we hypothesize that EMT-like alterations in liver cirrhosis are a side effect of high levels of TGF-beta and other pro-fibrotic mediators rather than a biological process converting functional parenchyma, i.e., hepatocytes, into myofibroblasts at a time when essential liver functions are deteriorating.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient

BACKGROUND The liver is one of the most important organs in the human body,with functions such as detoxification,digestion,and blood coagulation.In terms of vascular anatomy,the liver is divided into the left and the right liver by the main portal vein,and there are three hepatic efferent veins(right,middle,and left)and two portal branches.Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation,which may lead to an increase in the portal pressure gradient(PPG)and cause portal hypertension(PHT).In order to measure the increased pressure gradient of portal vein,the hepatic venous pressure gradient(HVPG)can be measured to reflect it in clinical practice.The accuracy of PPG measurements is directly related to patient prognosis.AIM To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT.METHODS From January 2017 to December 2019,102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed.RESULTS The mean HVPG of the middle hepatic vein was 17.47±10.25 mmHg,and the mean HVPG of the right and left hepatic veins was 16.34±7.60 and 16.52±8.15 mmHg,respectively.The average PPG was 26.03±9.24 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.15 and 0.02(P=0.164);0.25 and 0.05(P=0.013);and 0.14 and 0.02(P=0.013),respectively.The mean wedged hepatic vein/venous pressure(WHVP)of the middle and left hepatic veins was similar at 29.71±12.48 and 29.1±10.91 mmHg,respectively,and the mean WHVP of the right hepatic vein was slightly lower at 28.01±8.95 mmHg.The mean portal vein pressure was 34.11±8.56 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.26 and 0.07(P=0.009);0.38 and 0.15(P<0.001);and 0.26 and 0.07(P=0.008),respectively.The average free hepatic venous pressure(FHVP)of the right hepatic vein was lowest at 11.67±5.34 mmHg,and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19±4.88 and 11.67±5.34 mmHg,respectively.The average inferior vena cava pressure was 8.27±4.04 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.30 and 0.09(P=0.002);0.18 and 0.03(P=0.078);and 0.16 and 0.03(P=0.111),respectively.CONCLUSION Measurement of the middle hepatic vein HVPG could better represent PPG.Considering the high success rate of clinical measurement of the right hepatic vein,it can be the second choice.

Type 2 diabetes mellitus increases liver transplant-free mortality in patients with cirrhosis: A systematic review and meta-analysis

BACKGROUND The impact of type 2 diabetes mellitus(T2DM)on the prognosis and complications of liver cirrhosis is not fully clarified.AIM To clarify the mortality and related risk factors as well as complications in cirrhotic patients with T2DM.METHODS We searched PubMed,EMBASE,and the Cochrane Library from their inception to December 1,2020 for cohort studies comparing liver transplant-free mortality,hepatocellular carcinoma(HCC),ascites,spontaneous bacterial peritonitis(SBP),variceal bleeding,and hepatic encephalopathy(HE)in cirrhotic patients with vs without T2DM.Odds ratios(ORs)were combined by using fixed-effects or random-effects models with RevMan software.RESULTS The database search generated a total of 17 cohort studies that met the inclusion criteria.Among these studies,eight reported the risk of mortality,and eight reported the risk of HCC.Three studies provided SBP rates,and two documented ascites rates.Four articles focused on HE rates,and three focused on variceal bleeding rates.Meta-analysis indicated that T2DM was significantly associated with an increased risk of liver transplant-free mortality[OR:1.28,95%confidence intervals(CI):1.16-1.41,P<0.0001]and HCC incidence(OR:1.82,95%CI:1.32-2.51,P=0.003).The risk of SBP was not significantly increased(OR:1.1695%CI:0.86-1.57,P=0.34).Additionally,T2DM did not significantly increase HE(OR:1.3195%CI:0.97-1.77,P=0.08),ascites(OR:1.1195%CI:0.84-1.46,P=0.46),and variceal bleeding(OR:1.34,95%CI:0.99-1.82,P=0.06).CONCLUSION The findings suggest that cirrhotic patients with T2DM have a poor prognosis and high risk of HCC.T2DM may not be associated with an increased risk of SBP,variceal bleeding,ascites,or HE in cirrhotic patients with T2DM.

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension

BACKGROUND Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis(mPVTT) and cirrhotic portal hypertension(CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm.AIM To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS)combined with radioactive seed strand for the treatment of mPVTT patients with CPH.METHODS The clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data(success rate, relief of portal vein pressure and CPH symptoms,and adverse events), PVTT response, and patient survival were assessed through a 2-year followup.RESULTS The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure(22.25 ± 7.33mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo(range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%,and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo(95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage,and PVTT response were independent prognostic factors(P < 0.05).CONCLUSION TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-a/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia

Background and Aims:The role of platelet autophagy in cirrhotic thrombocytopenia(CTP)remains unclear.This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide(H_(2)S)on platelet autophagy.Methods:Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses.Autophagy markers(ATG7,BECN1,LC3,and SQSTM1)were quantified using enzyme-linked immunosorbent assay,while autophagosomes were visualized through electron microscopy.Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS(an H_(2)S donor),hydroxocobalamin(an H_(2)S scavenger),or AG 1295(a selective PDGFR-α/inhibitor).A carbon terachloride-induced cirrhotic BALB/c mouse model was established.Cirrhotic mice with thrombocytopenia were randomly treated with normal saline,NaHS,or hydroxocobalamin for 15 days.Changes in platelet count and aggregation rate were observed every three days.Results:Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H_(2)S levels,alongside increased platelet aggregation,compared to healthy controls.In vitro,NaHS treatment of platelets from severe CTP patients elevated LC3-II levels,reduced SQSTM1 levels,and decreased platelet aggregation in a dose-dependent manner.H_(2)S treatment inhibited PDGFR,PI3K,Akt,and mTOR phosphorylation.In vivo,NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice,reducing platelet aggregation without affecting the platelet count.Conclusions:Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients.H_(2)S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

Pharmacological management of portal hypertension:current status and future

Portal hypertension(PHT)is the trigger of the severe complications of cirrhosis,in eluding esophagogastric variceal bleeding(EVB),ascites,hepatic encephalopathy,cirrhotic cardiomyopathy,acute kidney injury and hepatorenal syndrome(AKI-HRS),which may cause death or increase the need for liver transplantation.11Of these,EVB remains one of the deadliest complications of PHT.As of now,the most widely accepted measure to assess portal pressure(PP)and PHT is the hepatic venous pressure gradient(HVPG)via transjugular-hepatic vein balloon catheterization?

Crosstalk between hepatic stellate cells and tumor cells in the development of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)ranks sixth in population age-standardized incidence(ASI)and fourth in population age-standardized mortality(ASM)globally and is the fourth ASI and the second ASM.