TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

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.

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.

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.

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.

RANDOMIZED CASE-CONTROLLED TRIAL OF ORAL LOW-DOSE ACYCLOVIR FOR PREVENTION OF VIRUS INFECTIONS IN RECIPIENTS OF RENAL ALLOGRAFTS

A randomized case-controlled trial of oral low-dose acyclovir (600-800 mg per day) has been conducted for the prevention of virus infections in 66 recipients of renal allografts since 1990. In comparison with the untreated controls, acyclovir could prevent herpes virus simplex (HSV), reduce morbidity of pneumonia from 10 cases (30%) to 3 cases (9%) (P<0.05) and lower CMV-IgM positive rate from 30% to 12%. Serum Cr and BUN in acyclovir group were lower than those in control group. These results strongly suggested that oral administration low-dose acyclovir could prevent virus infections after renal transplantation.

Hepatitis B virus infection in patients with Wilson disease:A large retrospective study

BACKGROUND Wilson disease(WD)is the most common genetic metabolic liver disease.Some studies have shown that comorbidities may have important effects on WD.Data on hepatitis B virus(HBV)infection in patients with WD are limited.AIM To investigate the prevalence and clinical impact of HBV infection in patients with WD.METHODS The clinical data of patients with WD were analyzed retrospectively,and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.RESULTS Among a total of 915 WD patients recruited,the total prevalence of current and previous HBV infection was 2.1%[95%confidence interval(CI):1.2%-3.0%]and 9.2%(95%CI:7.3%-11.1%),respectively.The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B(CHB)infection.The diagnosis of WD was missed in all but two patients with CHB infection.The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo,which was significantly longer than that in patients with isolated WD(10.5 mo).The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD(63.1%vs 19.3%,P=0.000 and 36.8%vs 4.1%,P<0.001,respectively).Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection[odds ratio(OR)=7.748;95%CI:2.890-20.774;P=0.000)]or previous HBV infection(OR=5.525;95%CI:3.159-8.739;P=0.000)than in patients with isolated WD.CONCLUSION The total prevalence of current HBV infection in patients with WD was 2.1%.The diagnosis of WD in CHB patients is usually missed.HBV infection is an independent risk factor for severe liver disease in WD patients.The diagnosis of WD should be ruled out in some patients with CHB infection.

Viruses and autism: A Bi-mutual cause and effect

Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.

The host type I interferon response to viral and bacterial infections

Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNsare produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN productionwere largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infectionsby recognizing various viral components. Furthermore, much progress has been made in defining the signaling path-ways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally importantin inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellularviral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also inducethe up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type IIFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. Thisreview will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.

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.

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.

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-α) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV.METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA.RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV(50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=-0.05).CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy.Response rate of SENV to the combination therapy depends on SENV DNA level.

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.

T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection

Hepatitis B is caused by the host immune response and T cells play a major role in the immunopathogenesis. More importantly,T cells not only destroy hepatocytes infected by hepatitis B virus(HBV),but also control HBV replication or eradicate HBV in a noncytolytic manner.Therefore,analysis of T cell immune response during acute and chronic HBV infection is important to develop a strategy for successful viral control,which could lead to immunotherapy for terminating persistent HBV infection.There have been many attempts at immunotherapy for chronic HBV infection,and some have shown promising results.High viral load has been shown to suppress antiviral immune responses and immunoinhibitory signals have been recently elucidated, therefore,viral suppression by nucleos(t)ide analogs, stimulation of antiviral immune response,and suppression of the immunoinhibitory signals must be combined to achieve desirable antiviral effects.

An overview of occult hepatitis B virus infection

Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication. The previous two decades have witnessed a remarkable progress in our understanding of OBI and its clinical implications. Appropriate diagnostic techniques must be adopted. Sensitive HBV DNA amplification assay is the gold standard assay for detection of OBI. Viral as well as host factors are implicated in the pathogenesis of OBI. However, published data reporting the infectivity of OBI by transfusion are limited. Several aspects including OBI transmission, infectivity and its relation to the development of chronic liver diseases and hepatocellular carcinoma have to be resolved. The aim of the present review is to highlight recent data on OBI with a focus on its virological diagnosis and clinical outcome.

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.

Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.

Hepatitis C virus associated glomerulopathies

Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type&#x02005;I&#x02005;MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-&#x003b1; plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.

Occult hepatitis B virus and hepatocellular carcinoma

Occult hepatitis B virus(HBV)infection(OBI)is a challenging pathobiological and clinical issue that has been widely debated for several decades.By definition,OBI is characterized by the persistence of HBV DNA in the liver tissue(and in some cases also in the serum)in the absence of circulating HBV surface antigen(HBsAg).Many epidemiological and molecular studies have indicated that OBI is an important risk factor for hepatocellular carcinoma(HCC)development.OBI may exert direct pro-oncogenic effects through the activation of the same oncogenic mechanisms that are activated in the course of an HBsAg-positive infection.Indeed,in OBI as in HBV-positive infection,HBV DNA can persist in the hepatocytes both integrated into the host genome as well as free episome,and may maintain the capacity to produce proteins-mainly X protein and truncated preS-S protein-provided with potential transforming properties.Furthermore,OBI may indirectly favor HCC development.It has been shown that the persistence of very low viral replicative activity during OBI may induce mild liver necro-inflammation continuing for life,and substantial clinical evidence indicates that OBI canaccelerate the progression of liver disease towards cirrhosis that is considered the most important risk factor for HCC development.

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.