Insights into gastrointestinal manifestation of human immunodeficiency virus:A narrative review

Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

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.

Multi-clustering study on the association between human leukocyte antigen-DP-DQ and hepatitis B virus-related hepatocellular carcinoma and cirrhosis in Viet Nam

BACKGROUND Human leukocyte antigen(HLA)class II molecules are cell surface receptor proteins found on antigen-presenting cells.Polymorphisms and mutations in the HLA gene can affect the immune system and the progression of hepatitis B.AIM To study the relation between rs2856718 of HLA-DQ,rs3077,and rs9277535 of HLA-DP,hepatitis B virus(HBV)-related cirrhosis,and hepatocellular carcinoma(HCC).METHODS In this case-control study,the genotypes of these single nucleotide polymorphisms(SNPs)were screened in 315 healthy controls,471 chronic hepatitis B patients,250 patients with HBV-related liver cirrhosis,and 251 patients with HCC using TaqMan real-time PCR.We conducted Hardy-Weinberg equilibrium and linkage disequilibrium tests on the genotype distributions of rs2856718,rs3077,and rs9277535 before hierarchical clustering analysis to build the complex interaction between the markers in each patient group.RESULTS The physical distance separating these SNPs was 29816 kB with the disequilibrium(D’)values ranging from 0.07 to 0.34.The close linkage between rs3077 and rs9277535 was attributed to a distance of 21 kB.The D’value decreased from moderate in the healthy control group(D’=0.50,P<0.05)to weak in the hepatic disease group(D’<0.3,P<0.05).In a combination of the three variants rs2856718,rs3077,and rs9277535,the A allele decreased hepatic disease risk[A-A-A haplotype,risk ratio(RR)=0.44(0.14;1.37),P<0.05].The G allele had the opposite effect[G-A/G-G haplotype,RR=1.12(1.02;1.23),P<0.05].In liver cancer cases,the A-A-A/G haplotype increased the risk of HCC by 1.58(P<0.05).CONCLUSION Rs9277535 affects liver fibrosis progression due to HBV infection,while rs3077 is associated with a risk of HBVrelated HCC.The link between rs2856718,rs3077,and rs9277535 and disease risk was determined using a multiclustering analysis.

Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide,with a 5-year relative survival rate of approximately 18%.The similarity between incidence and mortality(830000 deaths per year)underscores the bleak prognosis associated with the disease.HCC is the fourth most common malignancy and the second leading cause of cancer death in China.Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus(HBV)or hepatitis C virus(HCV)infection,alcoholism or alcoholic steatohepatitis,nonalcoholic fatty liver disease,or nonalcoholic steatohepatitis.Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC.Although the total number of human immunodeficiency virus(HIV)-infected patients is declining globally the incidence of HCC is increasing in HIVinfected patients,especially those who are coinfected with HBV or HCV.As a result,people infected with HIV still face unique challenges in terms of their risk of developing HCC.AIM To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection.METHODS The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed.Among these,27 patients underwent hepatectomy(operation group)and 29 patients received conservative treatment(nonoperation group).All patients signed informed consents in line with the provisions of medical ethics.The general data,clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified.RESULTS The median disease-free survival(DFS)and overall survival(OS)of HIV-HCC patients in the surgical group were 13 months and 17 months,respectively,and the median OS of patients in the nonsurgical group was 12 months.The OS of the surgical group was significantly longer than that of the control group(17 months vs 12 months,respectively;P<0.05).The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis,postoperative microvascular invasion(MVI),a CD4+T-cell count<200/μL,Barcelona stage C-D,and men who have sex with men(MSM;P<0.05).CONCLUSION Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination,late tumor detection,late BCLC stage,CD4+T<200/μL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy.In addition,there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV,Child-Pugh score,alpha-fetoprotein measurement value,and HART-efficient antiretroviral therapy after the diagnosis of HIV(P<0.05).Therefore,these factors may also affect the survival and prognosis of patients.

Effectiveness of onsite and online education in enhancing knowledge and use of human immunodeficiency virus pre-and postexposure prophylaxis

BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group.AIM To investigate the effects of both onsite and online health education on the knowledge of,and willingness to use,PrEP and PEP among individuals receiving PEP services.METHODS Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing,conducted from January 1 to June 30,2022.Health education was provided both onsite and online during follow-up.Surveys assessing knowledge of,and willingness to use,PrEP/PEP were administered at baseline and again at 24 wk post-intervention.RESULTS A total of 112 participants were enrolled in the study;105 completed the follow-up at week 24.The percentage of participants with adequate knowledge of,and willingness to use,PrEP significantly increased from 65.2%and 69.6%at baseline to 83.8%and 82.9%at the end of the intervention(both P<0.05).Similarly,those with adequate knowledge of,and willingness to use,PEP increased from 74.1%and 77.7%at baseline to 92.4%and 89.5%at week 24(P<0.05).Being between 31 years and 40 years of age,having a postgraduate degree or higher,and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP(both P<0.05).CONCLUSION The findings show that both onsite and online health education significantly improved the knowledge of,and increased willingness to use,PrEP and PEP in individuals utilizing PEP services.

Role of viruses in periodontitis:An extensive review of herpesviruses,human immunodeficiency virus,coronavirus-19,papillomavirus and hepatitis viruses

Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.

Oncological features and prognosis of colorectal cancer in human immunodeficiency virus-positive patients: A retrospective study

BACKGROUND Due to the prolonged life expectancy and increased risk of colorectal cancer(CRC)among patients with human immunodeficiency virus(HIV)infection,the prognosis and pathological features of CRC in HIV-positive patients require examination.AIM To compare the differences in oncological features,surgical safety,and prognosis between patients with and without HIV infection who have CRC at the same tumor stage and site.METHODS In this retrospective study,we collected data from HIV-positive and-negative patients who underwent radical resection for CRC.Using random stratified sampling,24 HIV-positive and 363 HIV-negative patients with colorectal adenocarcinoma after radical resection were selected.Using propensity score matching,we selected 72 patients,matched 1:2(HIV-positive:negative=24:48).Differences in basic characteristics,HIV acquisition,perioperative serological indicators,surgical safety,oncological features,and long-term prognosis were compared between the two groups.RESULTS Fewer patients with HIV infection underwent chemotherapy compared to patients without.HIV-positive patients had fewer preoperative and postoperative leukocytes,fewer preoperative lymphocytes,lower carcinoembryonic antigen levels,more intraoperative blood loss,more metastatic lymph nodes,higher node stage,higher tumor node metastasis stage,shorter overall survival,and shorter progression-free survival compared to patients who were HIV-negative.CONCLUSION Compared with CRC patients who are HIV-negative,patients with HIV infection have more metastatic lymph nodes and worse long-term survival after surgery.Standard treatment options for HIV-positive patients with CRC should be explored.

Hepatitis C virus eradication in people living with human immunodeficiency virus:Where are we now?

Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis,prognosis and recurrence risk in patients with cervical epithelioma

BACKGROUND Cervical intraepithelial neoplasia(CIN)is an important precursor of cervical cancer.Early detection and treatment can reduce the incidence of cervical cancer.AIM To investigate the detection rate of human papillomavirus(HPV)E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia(CIN)and its relationship with CIN progression and diagnosis.METHODS One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected.These patients were graded CIN based on colposcopy and cervical pathology.The positive expression rates of HPV E6/E7 mRNA and HPV[polymerase chain reaction(PCR)-reverse dot crossing]were compared among all groups.Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr.The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis.RESULTS The diagnostic sensitivity,specificity,and sensitivity of PCR-reverse point hybrid ization technology for secondary CIN were 70.41%,70.66%,and 0.714,respectively.Sensitivity and specificity for secondary CIN were 752%and 7853%,respectively,the area under the curve value was 0.789.Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I(P<0.05).In CIN grade I patients with positive for HPV E6/E7 mRNA,in its orientation to grade CIN patients,in its orientation to grade CIN patients,at 69.2%,compared with patients negative for HPV E6/E7 mRNA(30.8%),significant difference(P<0.05).CONCLUSION HPV E6/E7 mRNA and HPV(PCR-reverse dot hybrid)positive expression have a close relationship with CINgrade disease progression and is an independent risk factor for high-grade CIN lesions.

Human immunodeficiency virus cascade–continuum of care stages and outcomes in a hospital in southern Brazil

BACKGROUND The human immunodeficiency virus(HIV)continuum of care cascade illustrates the 90-90-90 goals defined by the Joint United Nations Program on HIV/acquired immunodeficiency syndrome(UNAIDS).The care cascade includes the following five steps:Diagnosis,linkage to care,retention in care,adherence to antiretroviral therapy(ART),and viral suppression.AIM To elaborate the HIV cascade of patients diagnosed with HIV at the Nossa Senhora da Conceição Hospital(HNSC)and to determine possible local causes for the loss of patients between each step of the cascade.METHODS This retrospective cohort study included patients diagnosed with HIV infection from January 1,2015 to December 31,2016 and followed up until July 31,2019.The data were analyzed by IBM SPSS software version 25,and Poisson regression with simple robust variance was used to analyze variables in relation to each step of the cascade.Variables with P<0.20 were included in multivariable analysis,and P<0.05 was considered significant.Pearson’sχ^(2) test was used to compare the groups of patients followed up at the HNSC and those followed up at other sites.RESULTS The results were lower than those expected by the UNAIDS,with 94%of patients linked,91%retained,81%adhering to ART,and 84%in viral suppression.Age and site of follow-up were the variables with the highest statistical significance.A comparison showed that the cascade of patients from the HNSC had superior results than outpatients,with a significant difference in the last step of the cascade.CONCLUSION The specialized and continued care provided at the HNSC was associated with better results and was closer to the goals set by the UNAIDS.The development of the HIV cascade using local data allowed for the stratification and evaluation of risk factors associated with the losses occurring between each step of the cascade.

Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

AIM:To investigate the peripheral T-lymphocyte subpopulation profile,and its correlations with hepatitis B virus(HBV) replication level in chronic HBV-infected(CHI) individuals with normal liver function tests(LFTs) . METHODS:Frequencies of T-lymphocyte subpopu-lations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection,and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis. RESULTS:CHI individuals had significantly decreased relative frequencies of CD3+,CD4+ subpopulationsand CD4+/CD8+ ratio,and increased CD8+ subset percentage compared with uninfected individuals(all P < 0.001) . There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations(ANOVA linear trend test P < 0.01) . The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers,and those having gained infection before the age of 8 years. In multiple regressions,after adjustment for age at HBV infection and status of maternal HBV infection,log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations,whereas the effect of HBeAg was not significant. CONCLUSION:HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.

Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes

Aim: To study the integration of hepatitis B virus (HBV) DNA into sperm chromosomes in hepatitis B patients and the features of its integration. Methods: Sperm chromosomes of 14 subjects (5 healthy controls and 9 HB patients, including 1 acute hepatitis B, 2 chronic active hepatitis B, 4 chronic persistent hepatitis B, 2 HBsAg chronic carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free hamster oocytes and human spermatozoa. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes. Results: Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis B. In 9(9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots and the others 2 to 4 signals. The fluorescence intensity showed significant difference among the signal spots. The distribution of signal sites among chromosomes seems to be random. Conclusion: HBV could integrate into human sperm chromosomes. Results suggest that the possibility of vertical transmission of HBV via the germ line to the next generation is present.

Expression of hepatitis B virus genes in early embryonic cells originated from hamster ova and human spermatozoa transfected with the complete viral genome

Aim： To detect the expression of hepatitis B virus （HBV） genes （HB S and C genes） in early embryonic cells after introducing motile human sperm carrying HBV DNA into zona-free hamster oocytes via the in vitro fertilization （IVF） technique. Methods： Human sperm-mediated HBV genes were delivered into zona-free hamster oocytes by the IVF method. Polymerase chain reaction （PCR） was used to detect HB S and pre-Core/Core （pre-C/C） coding genes both in one- and two-cell embryos. Reverse transcription-PCR （RT-PCR） analysis was used to study the expression of the two genes. Fluorescence in situ hybridization （FISH） analysis using the full-length HBV DNA as the hybridization probe was performed to confirm the integration of viral DNA in the host embryonic genome. Results： Both HB S and pre-C/C coding genes are present and transcribed in one- and two-cell embryos originated from hamster ova IVF with human spermatozoa carrying HBV DNA sequences. Conclusion： Sperm-mediated HBV genes are able to replicate and express themselves in early embryonic cells. These results provide direct evidence that HBV DNA could transmit vertically to the next generation via the male germ line.

Human immunodeficiency virus and hepatotropic viruses comorbidities as the inducers of liver injury progression

Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus(HBV) and hepatitis C virus(HCV) causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA) and antiretroviral therapy(ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals.

Gut epithelial barrier dysfunction in humanimmunodeficiency virus-hepatitis C virus coinfectedpatients:Influence on innate and acquired immunity

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

Immune therapy for human papillomaviruses-related cancers

Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered lowrisk such as HPV 6 and 11, produce warts; while highrisk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of precancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cellsby the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virushost interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.

Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases

Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.

Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus:a retrospective cohort study

AIM To assess the incidence of hepatocellular carcinoma(HCC) in chronic liver disease due to hepatitis B virus(HBV) or hepatitis C virus(HCV) coinfected with human immunodeficiency virus(HIV).METHODS A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review.RESULTS Of 804 patients were included(399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger(36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected(P < 0.001). HCC was diagnosed in 36 patients(10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years(95%CI: 0.12-0.46 vs 0.47-1.05)(long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC. CONCLUSION In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.

Autoimmune hepatitis in human immunodeficiency virus-infected patients: A case series and review of the literature

BACKGROUND Abnormal liver chemistry is a common problem in human immunodeficiency virus (HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity, and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals;however, this condition has been increasingly reported over the past few years. CASE SUMMARY We present 13 HIV-infected patients (5 males and 8 females) who developed autoimmune hepatitis (AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 106 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were 178 and 177 U/mL, respectively. Elevation of immunoglobulin G levels was present in 11 (85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11 (85%) and 5 (38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible with AIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications. CONCLUSION This report underscores the emergence of autoimmune hepatitis in the context of HIV infection.

Hepatitis C virus in human B lymphocytes transformed by Epstein-Barr virus in vitro by in situ reverse transcriptase-polymerase chain reaction

AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.