Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

HPV/HBV or HPV/HCV Co-Infections in Women Treated for Chronic Hepatitis at Hôpital Saint Camille in Ouagadougou, Burkina Faso

Introduction: Cervical cancer is a public health concern and is mainly caused by Human papillomaviruses (HPV). In many parts of the world, studies are being carried out to understand the different genotypes to better tackle this issue. We conducted a study to determine the prevalence of HPV genotypes in women with chronic hepatitis B or C infection, co-infected or not with HIV, treated at the Hôpital Saint Camille in Ouagadougou (Burkina Faso). Methods: This study was conducted from April to July 2023, including 100 women in gastroenterology at Hôpital Saint Camille. A questionnaire on their socio-demographic and life style was administrated;and endocervical samples were collected using sterile swabs and then sent to Centre of Biomolecular Research Pietro Annigoni (CERBA). HPV molecular detection and genotyping were performed by PCR and hybridization using the HPV Direct Flow Chips kit. Data were analysis using chi square test or Fischer’s exact test with a significance threshold for p Results: The prevalence of HPV infection was 28% (28/100) on the sample of women tested. The most frequent genotypes were HPV 52 (8.33%), followed by HPV 18 and 68 (6.25% each) for high-risk HPVs, and HPV 6, 44/55 and 62/81 (8.33% each) for low-risk HPVs. Conclusion: This study, the first of its kind in Burkina Faso on this group of the population, reveals that the most frequent genotypes found in this study are not included in the vaccine available in Burkina Faso (Gardasil®4).

Fulminant Hepatitis Associated with Chronic Consumption of 3,4-Methylenedioxy-Methamphetamine;Case Report

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).

Hepatitis A virus-associated acute acalculous cholecystitis in an adult-onset Still’s disease patient:A case report and review of the literature

BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adult-onset Still’s disease(AOSD).There are no reports of HAV-associated AAC in an AOSD patient.CASE SUMMARY Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD.The patient presented with an acute abdomen and hypotension.Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC,but there were no signs of anemia nor thrombocytopenia.Serological screening revealed anti-HAV IgM antibodies.Steroid treatment did not alleviate her symptoms,and she was referred for laparoscopic cholecystectomy.The resected gallbladder was hydropic without perforation,and her clinical signs gradually improved after surgery.CONCLUSION AAC can be caused by HAV in AOSD patients.It is crucial to search for the underlying etiology for AAC,especially uncommon viral causes.

Blood coagulation factors and platelet response to drug-induced hepatitis and hepatosis in rats

Background:Knowing the variability of blood coagulation responses to liver damage of different origins can provide a key to curing liver tissues or to mitigating treatment side effects.The aim of the present work was to compare the changes in the main components of hemostasis under experimental drug-induced hepatosis and hepatitis in rats.Methods:We modeled diclofenac-induced hepatitis and tetracycline-induced hepa-tosis.Hemostasis response was gauged by measuring fibrinogen,factor X,protein C(PC),and prothrombin in plasma.The decarboxylated form of prothrombin was de-tected by measuring prothrombin index and ecamulin index.Platelet reactivity was studied using aggregometry.Results:Both hepatitis and hepatosis decreased the synthesis of fibrinogen,factor X,and prothrombin.However,protein carboxylation was not disrupted in hepatosis but was much impaired in hepatitis.PC decreased in both models as a consequence of its consumption possibly during inflammatory response.Platelet aggregation rate was lower in hepatosis but higher in hepatitis.Conclusions:Our findings imply the need for a thorough monitoring of the hemostasis system in liver diseases to avoid possible thrombotic complications.Its state indicates the disorder's rate and character.

Autoimmune hepatitis and eosinophilia:A rare case report

BACKGROUND Autoimmune hepatitis consists of a chronic liver disease whose etiology is unknown.It is comprised of relevant immunological aspects and of immunemediated liver injury.Eosinophilia may be a considerable feature,particularly happening in male patients.CASE SUMMARY We report here a Crohn´s disease patient presenting with de novo hypergammaglobulinemia,circulating autoantibodies and elevated transaminase levels.He also had significant peripheral eosinophilia and elevated immunoglobulin E levels at diagnosis.The pathology findings from liver biopsy were compatible with autoimmune hepatitis with eosinophilic infiltration.CONCLUSION This is the first report of autoimmune hepatitis with exuberant eosinophilic infiltration in the liver and bone marrow,described in a patient with Crohn’s disease.

Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated,Preservative-free Hepatitis A Vaccine(Healive)in Children

Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.

Artificial intelligence and machine learning could support drug development for hepatitis A virus internal ribosomal entry sites

Hepatitis A virus(HAV)infection is still an important health issue worldwide.Although several effective HAV vaccines are available,it is difficult to perform universal vaccination in certain countries.Therefore,it may be better to develop antivirals against HAV for the prevention of severe hepatitis A.We found that several drugs potentially inhibit HAV internal ribosomal entry site-dependent translation and HAV replication.Artificial intelligence and machine learning could also support screening of anti-HAV drugs,using drug repositioning and drug rescue approaches.

From hepatitis A to E:A critical review of viral hepatitis

Viral infections affecting the liver have had an important impact on humanity,as they have led to significant morbidity and mortality in patients with acute and chronic infections.Once an unknown etiology,the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population.With the rapid scientific and technological advances in the last centuries,controlling and even curing the infections became a possibility,with a large focus on preventive medicine through vaccination.Hence,a comprehensive understanding of hepatitis A,B,C,D and E is required by primary care physicians and gastroenterologists to provide care to these patients.The review article describes the epidemiology,pathogenesis,clinical presentation,diagnostic tools and current medication regimens,with a focus on upcoming treatment options and the role of liver transplantation.

Primary Research of Immunological Mechanism of Combined Hepatitis A-Measles-Varicella Vaccine

To explore the primary humoral and cellular immunological mechanism of the combined hepatitis A-measles-varicella vaccine, the mice were inoculated with hepatitis A-measles-varicella vaccine by intraperitoneally and two weeks later, blood was collected to observe the mice＇s immunological status. Antibody level was measured to appraise the humoral immunity. At the same time, T lymphocyte surface marker, NK cell activity, LAK cell activity, delayed type hypersensitivity of skin, Mφ phagocytic function, mRNA level of cytokine IL-2 and IFN-γ plus lymphocyte transformation test were used to analyze the cellular immunity. The humoral immunity results show that the combined hepatitis A-measles-varicella vaccine produce the same antibody level as their corresponding univalent vaccine, and maintained fine immunogenicity and security. The result of cellular immunity shows that the combined vaccine could activate physical immunocyte, increase the regulative ability of cytokine, enhance the physical immune function and immune defense ability. The present research proved the security and better humoral and cellular immunity of combined hepatitis A-measles-varicella vaccine from the immunological point of view, which laid good foundation for further study and development.

False positive anti-hepatitis A virus immunoglobulin M in autoimmune hepatitis/primary biliary cholangitis overlap syndrome:A case report

BACKGROUND Autoimmune hepatitis(AIH)is an immune-mediated liver disease affecting all age groups.Associations between hepatitis A virus(HAV)and AIH have been described for many years.Herein,we report a case of an AIH/primary biliary cholangitis(PBC)overlap syndrome with anti-HAV immunoglobulin M(IgM)false positivity.CASE SUMMARY A 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness.He had marked transaminitis and hyperbilirubinemia.Viral serology was positive for HAV IgM and negative for others.Autoantibody screening was positive for anti-mitochondria antibody but negative for others.Abdominal ultrasound imaging was normal.He was diagnosed with acute hepatitis A.After symptomatic treatment,liver function tests gradually recovered.Several months later,his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal.Liver histology was prominent,and HAV RNA was negative.Therefore,AIH/primary biliary cholangitis(PBC)overlap syndrome diagnosis was made based on the“Paris Criteria”.The patient was successfully treated by immunosuppression.CONCLUSION This case highlights that autoimmune diseases or chronic or acute infections,may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies.Therefore,the detection of IgM should not be the only method for the diagnosis of acute HAV infection.HAV nucleic acid amplification tests should be employed to confirm the diagnosis.

Hepatitis A Virus PCR Analysis and <i>E. coli</i>Detection in Oysters at Oualidia Lagoon and Their Correlation

The present study aims to evaluate hepatitis A virus (HAV) prevalence and faecal contamination indicators Escherichia coli (E. coli) in oysters from Oualidia lagoon (Moroccan Atlantic coast) and to study the correlation between the two parameters. The survey was carried out on 87 samples of oysters (Crassostrea gigas) collected monthly between November 2015 and February 2017 from three sites corresponding to different oyster farms in the lagoon. Sanitary status of bivalve molluscs was assessed by E. coli enumeration using ISO 16649-3. Detection of hepatitis A virus, was carried out by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) according to ISO 15216-2 method. The prevalence of samples for which E. coli contamination exceeds the threshold of 230 E. coli/100g of flesh and intravalvular fluid (FIF) is 43%. HAV RNA was detected in 2% of the samples analyzed. This RNA was even detected in a sample meeting the bacterial criteria. Viral health surveillance of bivalve molluscs is therefore necessary before their delivery for human consumption.

Hepatitis A Antibody Seroprevalence in a Selected Kenyan Pediatric Population

The incidence of infection by Hepatitis A virus shows regional variation being highest in developing countries. Determination of age specific Hepatitis A virus (HAV) seroprevalence and the associated risk factors would help better plan for national preventive strategies including vaccination. We carried out a cross-sectional study on 300 children from Nairobi city, Kenya during the years 2003-2004. The age range of the children was 2 - 14 years and were from low and high socioeconomic status (SES) families. The indicators of SES included employment status, residence, number of children per patient’s household, parents’ level of education and source of drinking water. SES was encoded and analysed using Statistical Program for Social Sciences (SSPS) version 16.0. Seroprevalence increased significantly with advancing age. Seropositivity of HAV antibodies was significantly higher among children of low SES, 77.6% by the age of 14 years compared to children of high SES, 38.9% by the same age. Crowded household and parental education were significantly associated with high seropositivity and seronegativity respectively. There is significant rate of seronegativity amongst the studied population especially those from richer backgrounds making them more susceptible to severe infection in future with concomitant complications. We propose that revision of national vaccination program should be considered to include Hepatitis A vaccination.

Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NAFLD(CHB group,n = 51;CHB + NAFLD group,n = 57),and normal controls(normal group,n = 47) were recruited from Northern(Tianjin),Central(Shanghai),and Southern(Zhangzhou) China.Their PNPLA3 polymorphisms were genotyped by gene sequencing.The association between PNPLA3 polymorphisms and susceptibility to NAFLD,and clinical characteristics of NAFLD were evaluated on the basis of physical indices,liver function tests,glycolipid metabolism,and histopathologic scoring.The association of PNPLA3 polymorphisms and hepatitis B virus(HBV) load was determined by the serum level of HBV DNA.RESULTS:After adjusting for age,sex,and body mass index,we found that four linked single nucleotide polymorphisms(SNPs) of PNPLA3,including the rs738409 G allele(CHB + NAFLD group vs CHB group:odds ratio[OR]= 2.77,95%confidence interval[CI]:1.18-6.54;P = 0.02),rs3747206 T allele(CHB+ NAFLD group vs CHB group:OR = 2.77,95%CI:1.18-6.54;P = 0.02),rs4823173 A allele(CHB +NAFLD group vs CHB group:OR = 2.73,95%CI:1.16-6.44;P= 0.02),and rs2072906 G allele(CHB+ NAFLD group vs CHB group:OR = 3.05,95%CI:1.28-7.26;P = 0.01),conferred high risk to NAFLD in CHB patients.In patients with both CHB and NAFLD,these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis(NASH)(NAFLD activity score ≥3;P =0.01-0.03) and liver fibrosis(>1 Metavir grading;P =0.01-0.04).As compared to those with C/C and C/G at rs738409,C/C and C/T at rs3747206,G/G and G/A at rs4823173,and A/A and A/G at rs2072906,patients in the CHB + NAFLD group with G/G at rs738409,T/T at rs3747206,A/A at rs4823173,and G/G at rs2072906 showed significantly lower serum levels of HBV DNA(P< 0.01-0.05).CONCLUSION:Four linked SNPs of PNPLA3(rs738409,rs3747206,rs4823173,and rs2072906) are correlated with susceptibility to NAFLD,NASH,liver fibrosis,and HBV dynamics in CHB patients.

Hepatitis A:Epidemiology and prevention in developing countries

Hepatitis A is the most common form of acute viral hepatitis in the world.Major geographical differences in endemicity of hepatitis A are closely related to hygienic and sanitary conditions and other indicators of the level of socioeconomic development.The anti-hepatitis A virus(HAV)seroprevalence rate is presently decreasing in many parts of the world,but in less developed regions and in several developing countries,HAV infection is still very common in the first years of life and seroprev-alence rates approach 100%.In areas of intermediate endemicity,the delay in the exposure to the virus has generated a huge number of susceptible adolescents and adults and significantly increased the average age at infection.As the severity of disease increases with age,this has led to outbreaks of hepatitis A.Several factors contribute to the decline of the infection rate,including rising socioeconomic levels,increased access to clean water and the availability of a hepatitis A vaccine that was developed in the 1990s.For populations with a high proportion of susceptible adults,implementing vaccination programs may be considered.In this report,we review available epidemiological data and implementation of vaccination strategies,particularly focusing on developing countries.

Autoimmune hepatitis and IgG4-related disease

IgG4-related disease(IgG4-RD) is a chronic-fibroinflammatory disorder affecting a wide range of organs. Elevation of serum IgG4 concentrations and abundant infiltration of IgG4-expressing plasma cells are key diagnostic features of this autoimmune disease. Although common organ involvement of IgG4-RD includes the salivary glands, pancreas, and bile duct, hepatic involvement is less well established. Recently, five studies identified a subtype of autoimmune hepatitis(AIH), called IgG4-associated AIH(IgG4-AIH). IgG4-AIH is diagnosed based on significant accumulation of IgG4-expressing plasmacytes in the liver in patients who met the diagnostic criteria for classical AIH. Although four of the five reports regarded IgG4-AIH based on hepatic accumulation of IgG4-positive cells alone, one report diagnosed IgG4-AIH based on both hepatic accumulation of IgG4-positive cells and elevated serum concentrations of IgG4. IgG4-AIH diagnosed based on the latter criteria may be a hepatic manifestation of IgG4-RD whereas IgG4-AIH diagnosed based on the former criteria may be a subtype of AIH. In this review article, we summarize and discuss clinicopathological features of IgG4-AIH.

H2 strain attenuated live hepatitis A vaccines:protective efficacy in a hepatitis A outbreak

AIM To investigate the protective efficacy ofH2 strain attenuated live hepatitis A vaccines（H2-strain vaccines）in hepatitis A（HA）outbreaks.METHODS With the permission of theirparents,5551 pre-school and grade 1-3 primaryschool children were inoculated with 1 dose(106.5TCID50)of H2-strain vaccines in anonrandomized,controlled trial conducted inFucheng County,Hebei Province in May 1997.Another 6485 children in the same grades andcompatible in gender and age were enrolled ascontrols.Epidemiological and serological surveywas conducted to evaluate the protectiveefficacy of the vaccines.ELISA was used todetect serum IgM anti-HAV.RESULTS HA outbreak started in early May1998,peaked in the middle of the same month,and lasted about 80 days.Overall 302 HA caseswere found,192（53.58%）were 5-9 years old.One vaccinee and 25 control cases were found tohave hepatitis A,which account for 0.28%（1/356）and 5.92%（25/422）of all vaccinees andcontrols in the 14 villages,respectively.The protective efficacy of vaccines was 95.27%（95% Cl:85.83%-104.72%）.In subjects testedfor anti-HAV IgM from 13 villages,1（0.40%）overt and 11（4.06%）asymptomatic HAV caseswere found in 271 vaccinees,but 21（6.69%）ofovert and asymptomatic ones were found in 314controls.CONCLUSION H2 strain vaccines were excellent in preventing overt hepatitis A, but not so effective in preventing asymptomatic hepatitis A virus infection. A booster dose might be needed to get permanent reliable immunity.

Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy:A single center report of 8 cases

This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal range.Typical histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of autoimmune hepatitis,only one patient was classified with a definitive diagnosis of autoimmune hepatitis.Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding.The presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol abuse.CONCLUSION:Although possible,overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables.

Prognostic factors for chronic severe hepatitis and construction of a prognostic model

BACKGROUND: Chronic severe hepatitis is a serious illness with a high mortality rate. Discussion of prognostic judgment criteria for chronic severe hepatitis is of great value in clinical guidance. This study was designed to investigate the clinical and laboratory indices affecting the prognosis of chronic severe hepatitis and construct a prognostic model. METHODS: The clinical and laboratory indices of 213 patients with chronic severe hepatitis within 24 hours after diagnosis were analyzed retrospectively. Death or survival was limited to within 3 months after diagnosis. RESULTS: The mortality of all patients was 47.42%. Compared with the survival group, the age, basis of hepatocirrhosis, infection, degree of hepatic encephalopathy (HE) and the levels of total bilirubin (TBil), total cholesterol (CHO), cholinesterase (CHE), blood urea nitrogen (BUN), blood creatinine (Cr), blood sodium ion (Na), peripheral blood leukocytes (WBC), alpha-fetoprotein (AFP), international normalized ratio (INR) of blood coagulation and prothrombin time (PT) were significantly different in the group who died, but the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and hemoglobin (HGB) were not different between the two groups. At the same time, a regression model, Logit (P)=1.573xAge+1.338xHE-1.608xCHO+0.011xCr-0.109xNa+1.298xINR+11.057, was constructed by logistic regression analysis and the prognostic value of the model was higher than that of the MELD score. CONCLUSIONS: Multivariate analysis excels univariate anlysis in the prognosis of chronic severe hepatitis, and the regression model is of significant value in the prognosis of this disease.