Reactivation of hepatitis B virus infection – an important aspect of multifaceted problem

In this editorial we comment on the article published in the recent issue of the W orld Journal of Gastroenterology.We focus specifically on the problem of occult hepatitis B virus(HBV)infection,that is a result of previous hepatitis B(PHB)and a source for reactivation of HBV.The prevalence of PHB is underestimated due to the lack of population testing programs.However,this condition not only com-plicate anticancer treatment,but may be responsible for the development of other diseases,like cancer or autoimmune disorders.Here we unveil possible mecha-nisms responsible for realization of these processes and suggest practical approa-ches for diagnosis and treatment.

Perception of Medical Students towards Hepatitis B Virus Infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria

Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may influence the behavioral pattern and adoption of preventive measures against the virus and can affect the uptake of the Hepatitis B vaccine. This study assesses the perception of medical students towards Hepatitis B virus infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria. Methods: This was a descriptive cross-sectional study done in August 2021 among 236 clinical medical students using a multistage sampling technique. Data was collected using an interviewer-administered structured questionnaire and analysed using the IBM SPSS 28 (Statistical Package for the Social Sciences). Ethical approval was granted by Bingham University Teaching Hospital, Ethics Committee, Jos, Plateau State. Results: Two-thirds of respondents were of the opinion that they are at risk of contracting HBV. Half were of the opinion that the risk is very much while a third believed the risk is moderate. Among those who think they are not at risk of contracting HBV, the majority felt so because they are vaccinated while 10.3% believe that they are safe. 43.2% of respondents think that HBV Vaccine is very effective in preventing HBV infection while 39.8% think it is slightly effective, and 7.6% think it is not effective. Almost all respondents, 99.2% are of the opinion that HBV Vaccination is important for students while 0.8% think it is not important. The majority of the respondents at 95.8% were willing to be screened for HBV. The majority (85.6%) of respondents are willing to pay for HBV Vaccine as against 14.4% of respondents who are not willing to pay. Conclusion: Summarily, 21 (8.9%) of the students had a negative perception of Hepatitis B Vaccination, and 215 (91.1%) had a positive perception of Hepatitis B Vaccination. Perception-sustaining events like seminars, workshops, road shows, and campaigns should be organized among students and health workers.

Risk of hepatitis B virus reactivation in cancer patients undergoing treatment with tyrosine kinase-inhibitors

This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.

Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments

In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Chronic Hepatitis B in Indian Americans: Lack of Screening and Poor Linkage to Care

Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority populations, primarily owing to the high prevalence of CHB in their countries of origin. India is a country with a medium-to-high prevalence of hepatitis B (HB) (>2%) and has over 40 million people infected with hepatitis B virus (HBV), with more than 115,000 deaths annually from HBV-related complications. Indian Americans are one of the largest immigrant populations in the US but remain underdiagnosed and poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated the linkage-to-care (LTC) among Indian Americans to develop strategic plans to reduce the impact of HBV in the US. Methods: Between April 2022 and January 2024, serologic screening and surveys were provided to 328 Indian American adults (age 20 - 80) in New York City. All participants were tested for a triple panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). A survey was conducted on the subjects chronically infected with HBV regarding their histories of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics. Results: Of 328 screened and evaluated (246 males and 82 females), 10 (3.0%) were HBV-infected, 222 (67.7%) were susceptible to HBV, and 96 (29.3%) were immune. The prevalence of chronic HBV varied between the age groups: 4.6% (age 20 - 40), 3.4% (age 41 - 60), and 1.7% (age 61 - 80). Of 10 chronically infected, only two subjects had been previously diagnosed but were not engaged in care. Conclusion: HBV disproportionately affects Asian Americans, primarily owing to immigration from parts of the world where the disease is endemic. Indian Americans belong to an intermediate-risk group, with an HBV prevalence of >2%, but remain underdiagnosed and poorly linked to care. Our pilot study on Indian American populations, the first of its kind, demonstrates a 3% prevalence of CHB, none of whom are linked to care. In addition, this population has a high percentage of unimmune subjects, creating a large reservoir for future infection. With the growing population of Indian Americans, our findings can be used to develop community-based strategies for HBV screenings and LTC that target high-risk groups.

Chronic hepatitis B:Prevent,diagnose,and treat before the point of no return

Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions.Alarmingly,only about 13.4%of the individuals infected with this disease have been diagnosed,and awareness of hepatitis B virus(HBV)infection status is as low as 1%in sub-Saharan Africa.In 2022,CHB led to 1.1 million deaths globally.The World Health Organization(WHO)has set a target of eliminating hepatitis B as a public health concern by 2030;however,this goal appears increasingly unattainable due to multiple challenges.These challenges include low vaccination coverage;a large number of undiagnosed cases;a low proportion of patients eligible for treatment under current guidelines;limited access to healthcare;and the costs associated with lifelong treatment.Treatment of HBV can yield significant clinical benefits within a long window of opportunity.However,the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage.This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.

Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection:A case report

BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.

Chronic hepatitis B and occult infection in chemotherapy patients-evaluation in oncology and hemato-oncology settings:The CHOICE study

BACKGROUND Reactivation of hepatitis B virus(HBV)infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies,including cancer chemotherapy.HBV reactivation can cause significant morbidity and even mortality,which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis.AIM To determine the prevalence of chronic HBV(CHB)and occult HBV infection(OBI)among oncology and hematology-oncology patients undergoing chemo-therapy.METHODS In this observational study,the prevalence of CHB and OBI was assessed among patients receiving chemotherapy.Serological markers of HBV infection[hepatitis B surface antigen(HBsAg)/anti-hepatitis B core antigen(HBc)]were evaluated for all patients.HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc.RESULTS The prevalence of CHB in the study cohort was determined to be 2.3%[95%confidence interval(95%CI):1.0-4.2].Additionally,the prevalence of OBI among the study participants was found to be 0.8%(95%CI:0.2-2.3).CONCLUSION The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy.Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection,which can lead to increased morbidity and mortality.

New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection:Increase of entecavir dosage

Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.

Locked nucleic acid real-time polymerase chain reaction method identifying two polymorphisms of hepatitis B virus genotype C2 infections,rt269L and rt269I

BACKGROUND The presence of two distinct hepatitis B virus(HBV)Pol RT polymorphisms,rt269L and rt269I,could contribute to the unique clinical or virological phenotype of HBV genotype C2.Therefore,a simple and sensitive method capable of identifying both types in chronic hepatitis B(CHB)patients infected with genotype C2 should be developed.AIM To develop a novel simple and sensitive locked nucleic acid(LNA)-real timepolymerase chain reaction(RT-PCR)method capable of identifying two rt269 types in CHB genotype C2 patients.METHODS We designed proper primer and probe sets for LNA-RT-PCR for the separation of rt269 types.Using synthesized DNAs of the wild type and variant forms,melting temperature analysis,detection sensitivity,and endpoint genotyping for LNA-RT-PCR were performed.The developed LNA-RT-PCR method was applied to a total of 94 CHB patients of genotype C2 for the identification of two rt269 polymorphisms,and these results were compared with those obtained by a direct sequencing protocol.RESULTS The LNA-RT-PCR method could identify two rt269L and rt269I polymorphisms of three genotypes,two rt269L types[‘L1’(WT)and‘L2’]and one rt269I type(‘I’)in single(63 samples,72.4%)or mixed forms(24 samples,27.6%)in 87(92.6%sensitivity)of 94 samples from Korean CHB patients.When the results were compared with those obtained by the direct sequencing protocol,the LNA-RT-PCR method showed the same results in all but one of 87 positive detected samples(98.9%specificity).CONCLUSION The newly developed LNA-RT-PCR method could identify two rt269 polymorphisms,rt269L and rt269I,in CHB patients with genotype C2 infections.This method could be effectively used for the understanding of disease progression in genotype C2 endemic areas.

The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.

Pathogenesis of occult chronic hepatitis B virus infection

Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this"occult"HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

Role of occult hepatitis B virus infection in chronic hepatitis C

The development of sensitive assays to detect small amounts of hepatitis B virus(HBV) DNA has favored the identification of occult hepatitis B infection(OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV(HBs Ag) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody(antiHBc) in serum of HBs Ag-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C(CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma(HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC.

Elimination of hepatitis B as a public health threat:Addressing the challenge and taking action

Despite the significant efforts made in recent years,the latest data from the World Health Organization indicates that there are substantial challenges in achieving the elimination of hepatitis B virus(HBV)infection by 2030.The article in the World Journal of Hepatology by Ismael et al highlighted the limited accessibility to screening and antiviral treatment for HBV infection in eastern Ethiopia.Therefore,the editorial comments on this article will focus on the current challenges and recent efforts in the prevention and treatment of chronic hepatitis B,particularly emphasizing the expansion of screening and antiviral therapy,as well as feasible strategies to improve accessibility for HBV testing,antiviral therapy,and adherence enhancement.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

TT virus infection in patients with chronic hepatitis B and response of TTV to lamivudine

AIM: To investigate the responses of TT virus (TTV) and hepatitis B virus (HBV) to a long-term lamivudine therapy.METHODS: Sixteen patients infected with both TTV and HBV were treated with lamivudine 100 mg daily for 30 months. Blood samples were drawn at the beginning of the therapy and subsequently at month 3, 6, 9, 12 and 30.Serum TTV was quantified by real time PCR and serum HBV was detected by hybridization assay and nested polymerase chain reaction.RESULTS: TTV infection was detected in 100 % of HBV-infected patients. Loss of serum TTV DNA after one year of treatment occurred in 1/16 (6 %) patients. At the end of therapy, TTV DNA was positive in 94 % of them. The decline of HBV viremia was evident at 3 months after therapy and the response rate was 31%, 44 %, 63 %, 50 % and 50 %at month 3, 6, 9, 12 and 30, respectively.CONCLUSION: TTV replication is not sensitive to lamivudine and is highly prevalent in HBV-infected patients.

Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues

Hepatocellular carcinoma(HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus(HBV) infection(CHB) is the most important etiologic factor of this tumor, accounting for the development of more than50% of the cases in the world. Primary prevention ofHCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204(update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and environmental factors as evaluated in the world literature. Moreover, the benefits of antiviral treatment of CHB with nucleos/tide analogs, which have changed the natural history of the disease and have reduced but not eliminated the risk of HCC are also reviewed.

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure (ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections (BIs) trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first Bis either at admission or during hospitalization in patients with hepatitis B virus (HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016 The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4 To were community-acquired,46.4 To were healthcare-associated,and 40.2% belonged to nosocomial BIs.Pneumonia (40.7%),spontaneous bacterial peritonitis (SBP)(34.5%),and bloodstream infection (BSI)(13.4%) were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend (P=0.021).Sixty-one strains of bacteria,including 83.6% Gramnegative bacteria and 29.5% multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli (44.3%) and Klebsiella pneumoniae (23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend (ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;P <0.001).The independent predictors of the 28-doutcomes of patients with HBV-ACLF were COSSH-ACLF score (hazard ratio[HR]=1.371),acute kidney injury (HR=2.187),BSI (HR=2.339),prothrombin activity (HR=0.967),and invasive catheterization (HR=2.173).CONCLUSION For patients with HBV-ACLF combined with first BIs,pneumonia is the most common form,and the incidence of SBP decreases with increasing ACLF grade.COSSH-ACLF score,acute kidney injury,BSI,prothrombin activity,and invasive catheterization are the independent predictors of 28-d outcomes.

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.

Coinfection of TT virus and response to interferon therapy in patients with chronic hepatitis B or C

AIM: To investigate the serum positive percentage of TT virus (TTV) in patients with chronic hepatitis B or C and the response of the coinfected TTV to interferon (IFN) during IFN therapy for chronic hepatitis B and C. METHODS: We retrospectively studied the serum samples of 70 patients with chronic hepatitis who had received IFN-alpha therapy from January 1997 to June 2000, which included 40 cases of hepatitis B and 30 hepatitis C. All the patients had been followed up for at least 6 months after the end of IFN therapy. The serum TTV DNA was detected using the polymerase chain reaction (PCR) before and every month during the course of IFN treatment. RESULTS: TTV infection was detected in 15% (6/40) of the chronic hepatitis B group and 30% (9/30) of the chronic hepatitis C group. Loss of serum TTV DNA during IFN therapy occurred in 3 of 6 patients (50%) and 6 of 9 (67%) of hepatitis B and C groups, respectively. Seronegativity of TTV was found all during the first month of IFN therapy in the 9 patients. There was no correlation between the seroconversion of TTV and the biochemical changes of the patients. CONCLUSION: TTV is not infrequently coinfected in patients with chronic hepatitis B and C in Taiwan, and more than half of the TTV infections are IFN-sensitive. However, the loss of serum TTV DNA does not affect the clinical course of the patients with chronic hepatitis B or C.