AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 l...AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 liver samples from patients with chronic viral hepatitis, using immunohistochemistry with antibodies against c-kit, piclass glutathione S-transferase (pi-GST) and cytokeratins 19 (CK19). RESULTS: Oval cells were not observed in normal livers. In chronic viral hepatitis, hepatic oval cells were located predominantly in the periportal region and fibrosis septa,characterized by an ovoid nucleus, small size,and scant cytoplasm. Antibody against stem cell factor receptor, c-kit, had higher sensitivity and specificity than pi-GST and CK19. About 50%-70% of c-kit positive oval cells were stained positively for either pi-GST or CK19. CONCLUSION: Oval cells are frequently detected in human livers with chronic viral hepatitis, suggesting that oval cell proliferation is associated with the liver regeneration in this condition.展开更多
Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combin...Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.展开更多
According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase...According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.展开更多
BACKGROUND Human immunodeficiency virus(HIV)-positive patients coinfected with hepatitis B virus(HBV)are eligible for liver transplantation(LT)in Africa and Southeast Asia,particularly China.However,the outcome of HIV...BACKGROUND Human immunodeficiency virus(HIV)-positive patients coinfected with hepatitis B virus(HBV)are eligible for liver transplantation(LT)in Africa and Southeast Asia,particularly China.However,the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT(ABOi-LT)is unknown.AIM To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with endstage liver disease(ESLD).METHODS We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT.The pretransplantation HIV viral load was undetectable,with no active opportunistic infections.Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses,followed by an intraoperative regimen of intravenous immunoglobulin,methylprednisolone,and basiliximab.Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil,and prednisone.RESULTS At the intermediate-term follow-up,patients showed undetectable HIV viral load,CD4(+)T cell counts greater than 150 cells/μL,no HBV recurrence,and stable liver function.A liver allograft biopsy showed no evidence of acute cellular rejection.Both patients survived at 36-42 mo of follow-up.CONCLUSION This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes,suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.展开更多
AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis....AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis.METHODS: One hundred and twenty-one patients were divided into plasma exchange group and non-plasma exchange group, and were graded with MELD formula.The death rate was observed within 3 mo.RESULTS: Eighty-one patients died within 3 mo (35 cases in PE group, 46 cases in non-PE group). The mortality of patients in PE group whose MELD score between 20-30and 30-40 were 31.6% and 57.7%, respectively, but in non-PE cases they were 67.6%, 81.3% respectively.There was significant difference between PE group and non-PE group (P<0.05). However, the mortality of patients whose MELD score higher than 40 were 93.3% in PE group and 100% in non-PE group and there was no significant difference between the two groups (P= 0.65>0.05). The optimal cut-off values of MELD to predict the prognosis of patients were 30 in PE group whose sensitivity, specificity and C-statistic were 80.0%, 52.0% and 0.777, but in non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.CONCLUSION: The MELD score can act as a disease severity index for patients with severe viral hepatitis, and the mortality of the patient increases with the increase of the MELD score. The MELD can accurately predict the short-term prognosis of patients with severe viral hepatitis.展开更多
Context/Objectives: With the progression of the global epidemic of obesity and metabolic syndrome, the coexistence of hepatic steatosis in patients with chronic viral hepatitis B (VHB) is becoming significant. The aim...Context/Objectives: With the progression of the global epidemic of obesity and metabolic syndrome, the coexistence of hepatic steatosis in patients with chronic viral hepatitis B (VHB) is becoming significant. The aim of this work was to determine the factors associated with hepatic steatosis assessed by a Fibroscan with Controlled Attenuation Parameter (CAP) in patients with chronic viral hepatitis B in Côte d’Ivoire. Methods: This was a cross-sectional and analytical study. Data was collected from February 15 to July 31, 2020 in a private hospital structure in the city of Abidjan in Côte d’Ivoire. We included 83 patients with chronic viral hepatitis B. These were black patients, having performed a Fibroscan/CAP during the recruitment period and consenting to participate in the study. Patients with significant alcohol consumption, a secondary cause of hepatic steatosis, or other liver disease regardless of the etiology associated with hepatitis B were not included. Results: The frequency of hepatic steatosis in chronic VHB carriers assessed by the CAP in our study population was 48.19% including 24.10% severe steatosis. Obesity and high LDL cholesterol were statistically correlated with the presence of steatosis in our patients. Patients who had steatosis on ultrasound were 5 times more likely to have steatosis on CAP. Significant fibrosis was not significantly associated with steatosis. Conclusion: Obesity and LDL hypercholesterolemia are the main factors associated with hepatic steatosis detected by Fibroscan/CAP in patients with chronic viral hepatitis B.展开更多
AIM:To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort. METHODS:The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) fol...AIM:To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort. METHODS:The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) followed 29 490 HIVinfected individuals receiving medical care in 11 U.S. metropolitan areas for an average of 2.4 years,and a total of 69 487 person-years,between 1998 and 2004. ASD collected data on the presentation,treatment,and outcomes of HIV,including liver disease,hepatitis screening,and hepatitis diagnoses. RESULTS:Incident liver disease,chronic hepatitis B virus (HBV),and hepatitis C virus (HCV) were diagnosed in 0.9,1.8,and 4.7 per 100 person-years. HBV and HCV screening increased from fewer than 20% to over 60% during this period of observation (P < 0.001). Deaths occurred in 57% of those diagnosed with liver disease relative to 15% overall (P < 0.001). Overall 10% of deaths occurred among individuals with a diagnosis of liver disease. Despite care guidelines promoting screening and vaccination for HBV and screening for HCV,screening and vaccination were not universally conducted or,if conducted,not documented. CONCLUSION:Due to high rates of incident liver disease,viral hepatitis screening,vaccination,and treatment among HIV-infected individuals should be a priority.展开更多
Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden re...Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.展开更多
AIM: To establish a cell culture system with long-term replication of hepatitis C virus in vitro. METHODS: Human hepatoma cell line 7721 was tested for its susceptibility to HCV by incubating with a serum from a patie...AIM: To establish a cell culture system with long-term replication of hepatitis C virus in vitro. METHODS: Human hepatoma cell line 7721 was tested for its susceptibility to HCV by incubating with a serum from a patient with chronic hepatitis C. Cells and supernatant were harvested at various phases during the culturing periods. The presence of HCV RNA, the expression of HCV antigens in cells and/or supernatant were examined by RTPCR, in situ hybridization and immunohistochemistry respectively. RESULTS: The intracellular HCV RNA was first detected on d2 after infection and then could be intermittently detected in both cells and supernatant over a period of at least three months. The expression of HCV NS3,CP10 antigens could be observed in cells. The fresh cells could be infected by supernatant from cultured infected cells and the transmission of viral genome from HCV-infected 7721 cells to PBMCs was also observed. CONCLUSION: The hepatoma line 7721 is not only susceptible to HCV but also supports its long-term replication in vitro.展开更多
AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV...AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.展开更多
AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) p...AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) population in Nigeria.METHODS:HBV and HCV as well as HIV infections are endemic in sub Saharan Africa.This was a retrospective cohort study of 19 408 adults who were recruited between June 2004 and December 2010 in the AIDS Prevention Initiative in Nigeria in Nigeria programme at Jos University Teaching Hospital.Serological assays,including HBV surface antigen(HBsAg) and hepatitis C antibody were used to categorise hepatitis status of the patients.HBsAg was determined using enzyme immunoassay(EIA)(Monolisa HBsAg Ultra3;Bio-Rad).HCV antibody was tested using third generation EIA(DIA.PRO Diagnostic,Bioprobes srl,Milan,Italy).HIV RNA levels were measured using Roche COBAS Amplicor HIV-1 monitor test version 1.5(Roche Diagnostics,GmbH,Mannheim,Germany) with a detection limit of 400 copies/mL.Flow cytometry was used to determine CD4+ cell count(Partec,GmbH Munster,Germany).Comparison of categorical and continuous variables were achieved using Pearson's χ 2 and Kruskal Wallis tests respectively,on MedCalc for Windows,version 9.5.0.0(MedCalc Software,Mariakerke,Belgium).RESULTS:With an overall hepatitis screening rate of over 90% for each virus;HBV,HCV and HBV/HCV were detected in 3162(17.8%),1983(11.3%) and 453(2.5%) HIV infected adults respectively.The rate of liver disease was low,but highest among HIV monoinfected patients(29,0.11%),followed by HBV coinfected patients(15,0.08%).Patients with HBV coinfection and triple infection had higher log 10 HIV RNA loads(HBV:4.6 copies/mL vs HIV only:4.5 copies/mL,P<0.0001) and more severe immune suppression(HBV:645,55.4%;HBV/HCV:97,56.7%) prior to initiation of HAART compared to HIV mono-infected patients(1852,48.6%)(P<0.0001).Of 3025 patients who were 4.4 years on HAART and whose CD4 cell counts results at baseline and end of follow up were available for analyses,CD4 increase was significantly lower in those with HBV co-infection(HBV:144 cells/mm3 ;HBV/HCV:105 cells/mm3) than in those with HCV co-infection(165 cells/mm3) and HIV mono-infection(150 cells/mm3)(P=0.0008).CONCLUSION:High rates of HBV and HCV infections were found in this HIV cohort.CD4 recovery was significantly diminished in patients with HBV co-infection.展开更多
BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV p...BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.展开更多
AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control gr...AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P>0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.展开更多
Shared routes of transmission lead to frequent human immunodeficiency virus(HIV)-hepatitis B virus(HBV) coinfection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infectio...Shared routes of transmission lead to frequent human immunodeficiency virus(HIV)-hepatitis B virus(HBV) coinfection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liverdiseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV coinfection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome(genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study.展开更多
BACKGROUND Liver fibrosis can result in end-stage liver failure and death.AIM To examine human liver fibrogenesis and anti-fibrotic therapies,we evaluated the three dimensional ex vivo liver slice(LS)model.METHODS Fib...BACKGROUND Liver fibrosis can result in end-stage liver failure and death.AIM To examine human liver fibrogenesis and anti-fibrotic therapies,we evaluated the three dimensional ex vivo liver slice(LS)model.METHODS Fibrotic liver samples(F0 to F4 fibrosis stage according to the METAVIR score)were collected from patients after liver resection.Human liver slices(HLS)were cultivated for up to 21 days.Hepatitis C virus(HCV)infection,alcohol(ethanol stimulation)and steatosis(palmitate stimulation)were examined in fibrotic(F2 to F4)liver slices infected(or not)with HCV.F0-F1 HLS were used as controls.At day 0,either ursodeoxycholic acid(choleretic and hepatoprotective properties)and/or α-tocopherol(antioxidant properties)were added to standard of care on HLS and fibrotic liver slices,infected(or not)with HCV.Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzymelinked immunosorbent assay.RESULTS The cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs.Expression of the biomarkers of fibrosis and the progression to steatosis(estimated by triglycerides production)was increased with the addition of HCV and/or ethanol or palmitate.From day 15 of the follow-up studies,a significant decrease of both transforming growth factorβ-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures.CONCLUSION These results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver(viral,alcoholic,nonalcoholic steatohepatitis liver diseases)and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.展开更多
Acute liver failure(ALF)is a rare cause of liver-related mortality worldwide,with an estimated annual global incidence of more than one million cases.While drug-induced liver injury,including acetaminophen toxicity,is...Acute liver failure(ALF)is a rare cause of liver-related mortality worldwide,with an estimated annual global incidence of more than one million cases.While drug-induced liver injury,including acetaminophen toxicity,is the leading cause of ALF in the Western world,viral infections remain a significant cause of ALF and the most common cause in many developing nations.Given the high mortality rates associated with ALF,healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis,rapid treatment initiation when possible,and optimal management,which may include liver transplantation.This review aims to provide a summary of viral causes of ALF,diagnostic approaches,treatment options,and expected outcomes.展开更多
AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human...AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.展开更多
AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to ass...AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.展开更多
Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis.The causes are diverse and mainly associated with hepatotropic viruses,drug toxicity and metabolic...Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis.The causes are diverse and mainly associated with hepatotropic viruses,drug toxicity and metabolic disorders.Over the past decade,the aetiology of liver disease in kidney recipients has changed significantly.These relates to the use of direct-acting antiviral agents against hepatitis C virus,the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity.In addition,the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients.This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.展开更多
AIM:The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral ther...AIM:The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels.Moreover,a direct association has been observed between serum titers of HCV and transmission rates of the virus.The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease. METHODS:Fifty patients with HCV infection were included in the study.These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics.Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique.Linear regression analysis was performed between serum viral titers and liver tests.In addition,for the purpose of comparison,the subjects were divided into two groups:those with low viral liters (≤50 genome mEq/mL) and high titers (>50 mEq/mL). RESULTS:All subjects were men,with a mean±SD age of 47±7.8 years.The mean HCV RNA level in the blood was 76.3×10~5±109.1 genome equivalents/mL.There was no correlation between HCV RNA levels and age of the patients (r=0.181),and the history or amount (g/d) of alcohol consumption (r=0.07).Furthermore,no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r=0.175),bilirubin (r=0.217),ALT (r=0.06) and AST (r=0.004) levels.Similarly,no significant difference was observed between patients with low viral titers and high liters with respect to any of the parameters. CONCLUSION:Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus.These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.展开更多
文摘AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 liver samples from patients with chronic viral hepatitis, using immunohistochemistry with antibodies against c-kit, piclass glutathione S-transferase (pi-GST) and cytokeratins 19 (CK19). RESULTS: Oval cells were not observed in normal livers. In chronic viral hepatitis, hepatic oval cells were located predominantly in the periportal region and fibrosis septa,characterized by an ovoid nucleus, small size,and scant cytoplasm. Antibody against stem cell factor receptor, c-kit, had higher sensitivity and specificity than pi-GST and CK19. About 50%-70% of c-kit positive oval cells were stained positively for either pi-GST or CK19. CONCLUSION: Oval cells are frequently detected in human livers with chronic viral hepatitis, suggesting that oval cell proliferation is associated with the liver regeneration in this condition.
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region (No.2022D01C173)National Natural Science Foundation of China (No.81760832)。
文摘Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.
基金Supported by the Shenzhen Science and Technology R&D Fund,No.JCYJ20220530163011026Shenzhen Third People’s Hospital,No.G2022008 and No.G2021008.
文摘According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.
基金Supported by The Third People's Hospital of Shenzhen Scientific Research Project,No.G2021008 and No.G2022008Shenzhen Key Medical Discipline Construction Fund,No.SZXK079Shenzhen Science and Technology Research and Development Fund,No.JCYJ20210324131809027 and No.JCYJ20220530163011026.
文摘BACKGROUND Human immunodeficiency virus(HIV)-positive patients coinfected with hepatitis B virus(HBV)are eligible for liver transplantation(LT)in Africa and Southeast Asia,particularly China.However,the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT(ABOi-LT)is unknown.AIM To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with endstage liver disease(ESLD).METHODS We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT.The pretransplantation HIV viral load was undetectable,with no active opportunistic infections.Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses,followed by an intraoperative regimen of intravenous immunoglobulin,methylprednisolone,and basiliximab.Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil,and prednisone.RESULTS At the intermediate-term follow-up,patients showed undetectable HIV viral load,CD4(+)T cell counts greater than 150 cells/μL,no HBV recurrence,and stable liver function.A liver allograft biopsy showed no evidence of acute cellular rejection.Both patients survived at 36-42 mo of follow-up.CONCLUSION This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes,suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.
文摘AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis.METHODS: One hundred and twenty-one patients were divided into plasma exchange group and non-plasma exchange group, and were graded with MELD formula.The death rate was observed within 3 mo.RESULTS: Eighty-one patients died within 3 mo (35 cases in PE group, 46 cases in non-PE group). The mortality of patients in PE group whose MELD score between 20-30and 30-40 were 31.6% and 57.7%, respectively, but in non-PE cases they were 67.6%, 81.3% respectively.There was significant difference between PE group and non-PE group (P<0.05). However, the mortality of patients whose MELD score higher than 40 were 93.3% in PE group and 100% in non-PE group and there was no significant difference between the two groups (P= 0.65>0.05). The optimal cut-off values of MELD to predict the prognosis of patients were 30 in PE group whose sensitivity, specificity and C-statistic were 80.0%, 52.0% and 0.777, but in non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.CONCLUSION: The MELD score can act as a disease severity index for patients with severe viral hepatitis, and the mortality of the patient increases with the increase of the MELD score. The MELD can accurately predict the short-term prognosis of patients with severe viral hepatitis.
文摘Context/Objectives: With the progression of the global epidemic of obesity and metabolic syndrome, the coexistence of hepatic steatosis in patients with chronic viral hepatitis B (VHB) is becoming significant. The aim of this work was to determine the factors associated with hepatic steatosis assessed by a Fibroscan with Controlled Attenuation Parameter (CAP) in patients with chronic viral hepatitis B in Côte d’Ivoire. Methods: This was a cross-sectional and analytical study. Data was collected from February 15 to July 31, 2020 in a private hospital structure in the city of Abidjan in Côte d’Ivoire. We included 83 patients with chronic viral hepatitis B. These were black patients, having performed a Fibroscan/CAP during the recruitment period and consenting to participate in the study. Patients with significant alcohol consumption, a secondary cause of hepatic steatosis, or other liver disease regardless of the etiology associated with hepatitis B were not included. Results: The frequency of hepatic steatosis in chronic VHB carriers assessed by the CAP in our study population was 48.19% including 24.10% severe steatosis. Obesity and high LDL cholesterol were statistically correlated with the presence of steatosis in our patients. Patients who had steatosis on ultrasound were 5 times more likely to have steatosis on CAP. Significant fibrosis was not significantly associated with steatosis. Conclusion: Obesity and LDL hypercholesterolemia are the main factors associated with hepatic steatosis detected by Fibroscan/CAP in patients with chronic viral hepatitis B.
文摘AIM:To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort. METHODS:The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) followed 29 490 HIVinfected individuals receiving medical care in 11 U.S. metropolitan areas for an average of 2.4 years,and a total of 69 487 person-years,between 1998 and 2004. ASD collected data on the presentation,treatment,and outcomes of HIV,including liver disease,hepatitis screening,and hepatitis diagnoses. RESULTS:Incident liver disease,chronic hepatitis B virus (HBV),and hepatitis C virus (HCV) were diagnosed in 0.9,1.8,and 4.7 per 100 person-years. HBV and HCV screening increased from fewer than 20% to over 60% during this period of observation (P < 0.001). Deaths occurred in 57% of those diagnosed with liver disease relative to 15% overall (P < 0.001). Overall 10% of deaths occurred among individuals with a diagnosis of liver disease. Despite care guidelines promoting screening and vaccination for HBV and screening for HCV,screening and vaccination were not universally conducted or,if conducted,not documented. CONCLUSION:Due to high rates of incident liver disease,viral hepatitis screening,vaccination,and treatment among HIV-infected individuals should be a priority.
文摘Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.
基金Suppprted by the Mational Natural Science Foundation of China,No.39670672.
文摘AIM: To establish a cell culture system with long-term replication of hepatitis C virus in vitro. METHODS: Human hepatoma cell line 7721 was tested for its susceptibility to HCV by incubating with a serum from a patient with chronic hepatitis C. Cells and supernatant were harvested at various phases during the culturing periods. The presence of HCV RNA, the expression of HCV antigens in cells and/or supernatant were examined by RTPCR, in situ hybridization and immunohistochemistry respectively. RESULTS: The intracellular HCV RNA was first detected on d2 after infection and then could be intermittently detected in both cells and supernatant over a period of at least three months. The expression of HCV NS3,CP10 antigens could be observed in cells. The fresh cells could be infected by supernatant from cultured infected cells and the transmission of viral genome from HCV-infected 7721 cells to PBMCs was also observed. CONCLUSION: The hepatoma line 7721 is not only susceptible to HCV but also supports its long-term replication in vitro.
基金the Universidad de Buenos Aires(SECyT-UBA,TB14)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET,PIP723)+1 种基金Agencia Nacional de Promoción Científica y Tecnológica(ANPCyT,PICT 01610)Ministerio de Salud Pǘblica de la Nación(Beca Carrillo-Oativia)
文摘AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.
基金Supported by The United States Health Resources and Services Administration (U51HA02522-01-01)the Prevention of Liver Fibrosis and Carcinoma in Africa (PROLIFICA) project(EU-Framework 7)+1 种基金the United Kingdom National Institute for Healthcare Research (NIHR)the London Clinic Research Fellowship Scheme
文摘AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) population in Nigeria.METHODS:HBV and HCV as well as HIV infections are endemic in sub Saharan Africa.This was a retrospective cohort study of 19 408 adults who were recruited between June 2004 and December 2010 in the AIDS Prevention Initiative in Nigeria in Nigeria programme at Jos University Teaching Hospital.Serological assays,including HBV surface antigen(HBsAg) and hepatitis C antibody were used to categorise hepatitis status of the patients.HBsAg was determined using enzyme immunoassay(EIA)(Monolisa HBsAg Ultra3;Bio-Rad).HCV antibody was tested using third generation EIA(DIA.PRO Diagnostic,Bioprobes srl,Milan,Italy).HIV RNA levels were measured using Roche COBAS Amplicor HIV-1 monitor test version 1.5(Roche Diagnostics,GmbH,Mannheim,Germany) with a detection limit of 400 copies/mL.Flow cytometry was used to determine CD4+ cell count(Partec,GmbH Munster,Germany).Comparison of categorical and continuous variables were achieved using Pearson's χ 2 and Kruskal Wallis tests respectively,on MedCalc for Windows,version 9.5.0.0(MedCalc Software,Mariakerke,Belgium).RESULTS:With an overall hepatitis screening rate of over 90% for each virus;HBV,HCV and HBV/HCV were detected in 3162(17.8%),1983(11.3%) and 453(2.5%) HIV infected adults respectively.The rate of liver disease was low,but highest among HIV monoinfected patients(29,0.11%),followed by HBV coinfected patients(15,0.08%).Patients with HBV coinfection and triple infection had higher log 10 HIV RNA loads(HBV:4.6 copies/mL vs HIV only:4.5 copies/mL,P<0.0001) and more severe immune suppression(HBV:645,55.4%;HBV/HCV:97,56.7%) prior to initiation of HAART compared to HIV mono-infected patients(1852,48.6%)(P<0.0001).Of 3025 patients who were 4.4 years on HAART and whose CD4 cell counts results at baseline and end of follow up were available for analyses,CD4 increase was significantly lower in those with HBV co-infection(HBV:144 cells/mm3 ;HBV/HCV:105 cells/mm3) than in those with HCV co-infection(165 cells/mm3) and HIV mono-infection(150 cells/mm3)(P=0.0008).CONCLUSION:High rates of HBV and HCV infections were found in this HIV cohort.CD4 recovery was significantly diminished in patients with HBV co-infection.
基金Supported by the Mayo Clinic Center for Clinical and Translational Science from the National Center for Advancing Translational Sciences (5UL1TR000135-10)the Mayo Clinic Hepatobiliary SPORE from the National Cancer Institute (5P50CA210964-04)+1 种基金the Mayo Clinic Center for Cell Signaling in Gastroenterology (5P30DK084567-14)Gilead Sciences,Inc.(IN-US-174-0230)
文摘BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.
文摘AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P>0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.
文摘Shared routes of transmission lead to frequent human immunodeficiency virus(HIV)-hepatitis B virus(HBV) coinfection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liverdiseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV coinfection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome(genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study.
基金the Institut National de la Santéet de la Recherche Médicale(INSERM,France)and by Institut Pasteur(Paris,France)Daria Kartasheva-Ebertz received a PhD Fellowship from Assistance Publique-Hôpitaux de Paris(APHP,France).
文摘BACKGROUND Liver fibrosis can result in end-stage liver failure and death.AIM To examine human liver fibrogenesis and anti-fibrotic therapies,we evaluated the three dimensional ex vivo liver slice(LS)model.METHODS Fibrotic liver samples(F0 to F4 fibrosis stage according to the METAVIR score)were collected from patients after liver resection.Human liver slices(HLS)were cultivated for up to 21 days.Hepatitis C virus(HCV)infection,alcohol(ethanol stimulation)and steatosis(palmitate stimulation)were examined in fibrotic(F2 to F4)liver slices infected(or not)with HCV.F0-F1 HLS were used as controls.At day 0,either ursodeoxycholic acid(choleretic and hepatoprotective properties)and/or α-tocopherol(antioxidant properties)were added to standard of care on HLS and fibrotic liver slices,infected(or not)with HCV.Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzymelinked immunosorbent assay.RESULTS The cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs.Expression of the biomarkers of fibrosis and the progression to steatosis(estimated by triglycerides production)was increased with the addition of HCV and/or ethanol or palmitate.From day 15 of the follow-up studies,a significant decrease of both transforming growth factorβ-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures.CONCLUSION These results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver(viral,alcoholic,nonalcoholic steatohepatitis liver diseases)and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.
文摘Acute liver failure(ALF)is a rare cause of liver-related mortality worldwide,with an estimated annual global incidence of more than one million cases.While drug-induced liver injury,including acetaminophen toxicity,is the leading cause of ALF in the Western world,viral infections remain a significant cause of ALF and the most common cause in many developing nations.Given the high mortality rates associated with ALF,healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis,rapid treatment initiation when possible,and optimal management,which may include liver transplantation.This review aims to provide a summary of viral causes of ALF,diagnostic approaches,treatment options,and expected outcomes.
文摘AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.
文摘AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.
基金Supported by the Croatian Science Foundation,Project:Emerging and Neglected Hepatotropic Viruses after Solid Organ and Hematopoietic Stem Cell Transplantation,No.IP-2020-02-7407(to Mrzljak A).
文摘Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis.The causes are diverse and mainly associated with hepatotropic viruses,drug toxicity and metabolic disorders.Over the past decade,the aetiology of liver disease in kidney recipients has changed significantly.These relates to the use of direct-acting antiviral agents against hepatitis C virus,the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity.In addition,the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients.This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.
文摘AIM:The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels.Moreover,a direct association has been observed between serum titers of HCV and transmission rates of the virus.The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease. METHODS:Fifty patients with HCV infection were included in the study.These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics.Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique.Linear regression analysis was performed between serum viral titers and liver tests.In addition,for the purpose of comparison,the subjects were divided into two groups:those with low viral liters (≤50 genome mEq/mL) and high titers (>50 mEq/mL). RESULTS:All subjects were men,with a mean±SD age of 47±7.8 years.The mean HCV RNA level in the blood was 76.3×10~5±109.1 genome equivalents/mL.There was no correlation between HCV RNA levels and age of the patients (r=0.181),and the history or amount (g/d) of alcohol consumption (r=0.07).Furthermore,no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r=0.175),bilirubin (r=0.217),ALT (r=0.06) and AST (r=0.004) levels.Similarly,no significant difference was observed between patients with low viral titers and high liters with respect to any of the parameters. CONCLUSION:Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus.These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.