Hepatitis In Immunocompromised Patients Research Articles

Abnormal liver function in children hospitalized with acute respiratory infection of adenoviruses: a retrospective study.

Human adenoviruses (HAdVs) can cause acute hepatitis in immunocompromised patients. However, it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children. In this study, the liver function test (LFT) results were retrospectively analyzed among children hospitalized (age < 14 years) between January 2016 and October 2019 for acute respiratory infection caused by adenoviruses. Alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were elevated in 7.74% and 46.89% of patients, respectively. All patients with > 2 folds of the upper limit of ALT or AST levels were infected with HAdV-7 or HAdV-55. Significantly higher levels of ALT, AST, γ-glutamyl transpeptidase (γ-GT), and lower albumin levels were observed in the HAdV-7 infection group than in the HAdV-3 infection group. HAdV-55 infection led to significantly higher γ-GT, total bilirubin, and direct bilirubin levels than the other infection types. The records of four patients with serial monitoring of the LFT results were further analyzed. Multiple indicators remained abnormal during the entirehospitalization in these patients. These results indicate that HAdV infection is often accompanied by abnormal liver function, and HAdV-7 and HAdV-55 might be under-recognized contributors to hepatitis among children.

Abnormal liver function in children hospitalized with acute respiratory infection of adenoviruses: a retrospective study

Human adenoviruses (HAdVs) can cause acute hepatitis in immunocompromised patients. However, it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children. In this study, the liver function test (LFT) results were retrospectively analyzed among children hospitalized (age <14 years) between January 2016 and October 2019 for acute respiratory infection caused by adenoviruses. Alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were elevated in 7.74% and 46.89% of patients, respectively. All patients with >2 folds of the upper limit of ALT or AST levels were infected with HAdV-7 or HAdV-55. Significantly higher levels of ALT, AST, γ-glutamyl transpeptidase (γ-GT), and lower albumin levels were observed in the HAdV-7 infection group than in the HAdV-3 infection group. HAdV-55 infection led to significantly higher γ-GT, total bilirubin, and direct bilirubin levels than the other infection types. The records of four patients with serial monitoring of the LFT results were further analyzed. Multiple indicators remained abnormal during the entire hospitalization in these patients. These results indicate that HAdV infection is often accompanied by abnormal liver function, and HAdV-7 and HAdV-55 might be under-recognized contributors to hepatitis among children.

Hepatitis E Virus in Finland: Epidemiology and Risk in Blood Donors and in the General Population.

Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016-2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6-7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients.

Review of analytical and bioanalytical techniques for the determination of first-line anticytomegalovirus drugs

• Cytomegalovirus (CMV) being a major threat and fatal in immunocompromised patient can be treated with valganciclovir and Ganciclovir. • Physicochemical properties, pharmacological properties, mechanism of action of Valganciclovir and Ganciclovir are compared and conferred with their benefits in treating CMV. • Key findings and applications of different techniques for the determination of Valganciclovir and Ganciclovir are critically discussed. • This critical discussion would aid future researchers on analysing Valganciclovir and Ganciclovir. Cytomegalovirus (CMV) is a common virus which infects people of all ages. It causes serious illness like mononucleosis or hepatitis in immunocompromised patients. Ganciclovir had been the first drug of choice to treat cytomegalovirus infection. At present, Valganciclovir, the prodrug, is more predominantly used because of its higher oral bioavailability. Both the drugs act by inhibiting the replication of viral DNA. Commercially, ganciclovir is available in the form of capsules, suspensions, injections, nanoparticles and microspheres while valganciclovir is available as tablets and injections. This review provides an overview of physicochemical, pharmacokinetic and pharmacodynamic properties of ganciclovir and valganciclovir and a detailed investigation on different analytical techniques used for detection and quantification of these drugs on various matrices. Various techniques like spectroscopy, chromatography, electrochemical methods and hyphenated techniques were reported to determine ganciclovir and valganciclovir, either alone or in combination with other drugs, in different kinds of matrices like in bulk, existing dosage forms and also biological samples like plasma, serum, urine and myocardial tissue. Among various techniques used, HPLC, LC-MS systems are more commonly used because of their high sensitivity. This article summarizes the research works carried out since 1985 and intents to act as a handbook for future researchers.

Screening for hepatitis E virus genotype 3 in red deer (Cervus elaphus) and fallow deer (Dama dama), Portugal, 2018-2020.

Hepatitis E virus (HEV) genotype 3 is the most prevalent HEV genotype in Europe causing mostly asymptomatic infections in humans, but can also sporadically cause severe acute hepatitis, chronic liver disease, chronic hepatitis in immunocompromised patients and extra-hepatic manifestations. Although much is today known about the swine reservoir, no information is available on the occurrence of HEV from widely distributed deer species in Portugal. Here, we investigated the presence and characterized HEV in free-living deer in Portugal by screening stools from red deer (Cervus elaphus) (n=95) and fallow deer (Dama dama) (n=35) for HEV by a broad-spectrum nested RT-PCR, followed by sequencing and phylogenetic analysis. Two red deer females, sampled in central Portugal, showed to be shedding HEV (2.1%; 95% confidence interval: 0.58-7.35). Sequencing and genetic characterization showed that these two deer HEV sequences were 98.96% identical to each other, being both of HEV genotype 3 subgenotype 3e. The increasing numbers and distribution of deer in Portugal and the zoonotic features of the circulating HEV genotype 3 subgenotype 3e highlights the importance of continued surveillance directed to food-borne diseases, especially those involving wild animals and deer in particular.

Treatment for chronic hepatitis E virus infection: A systematic review and meta-analysis.

Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty‐four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta‐analysis of 395 patients showed a pooled SVR rate of 78% (95‐CI 72%–84%) after ribavirin treatment. Twenty‐five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon‐alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon‐alpha increases the risk of transplant rejection and should therefore be administered with great caution.

Hepatitis E virus infections in Europe

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The systematic use of improved tools for diagnosing and genotyping has completely changed our understanding of the epidemiology and clinical consequences of HEV infection. Most cases of HEV in Europe arise from infected animals such as pigs, wild boar, deer and rabbits. Zoonotic HEV genotypes (HEV genotypes 3–8) are mainly food-borne or transmitted by direct contact, but recent data suggest that infection can also be water-borne or even iatrogenic throught contamined blood products.HEV-3 is the most prevalent genotype in Europe but the geographic distributions of the 3 major clades and subgenotypes (HEV-3abjkchi, HEV-3efg, and HEV-3ra) differ. Most HEV-3 infections are asymptomatic but they can result in severe acute hepatitis in patients with chronic liver disease, chronic hepatitis in immunocompromised patients, and to extra-hepatic manifestations.Despite more frequent reports of symptomatic hepatitis E cases across Europe, systems for monitoring HEV infections vary greatly. Severe HEV-associated illnesses, hospitalizations and deaths are probably underestimated. The seroprevalence and incidence of locally acquired hepatitis E varies between and within European countries and over time. The precise origin of these variations is uncertain but may be linked to environmental factors or the degree to which HEV contaminates the human food chain. Collaborative initiatives such as the establishment of the One Health platform for HEV sequences (HEVnet database) will be very useful for a better understanding of the epidemiology of HEV in Europe and the development of effective prevention strategies.

Vývoj poznatků o nemoci způsobené virem hepatitidy E

Hepatitis E virus (HEV) infection is one of the most common causes of acute hepatitis worldwide. The Czech Republic is also a region with a natural occurrence of HEV genotype 3. Diseases caused by different genotypes have distinct clinical and epidemiological characteristics. In industrialized countries, numerous local animal reservoirs have been described and infection is considered to be zoonotic disease in these areas. The most significant route of transmission is through ingestion of insufficiently cooked meat of reservoir animals. In addition, numerous extrahepatic manifestations, even without dominant liver disease, and the possibility of chronic hepatitis in immunocompromised patients have been described. The review summarizes the current knowledge of HEV related disease and current approaches to the treatment of acute and chronic hepatitis E.

Epidemiology of Hepatitis E in England and Wales: A 10-Year Retrospective Surveillance Study, 2008-2017.

Indigenous, foodborne transmission of hepatitis E virus genotype 3 (HEV G3) has become recognized as an emerging problem in industrialized countries. Although mostly asymptomatic, HEV G3 infection has a range of outcomes, including mild illness, severe acute hepatitis, and, of particular concern, chronic progressive hepatitis in immunocompromised patients. Public Health England has monitored cases of acute HEV infection in England and Wales since 2003. Between 2010 and 2017, enhanced surveillance using 2 linked laboratory databases and questionnaires on clinical features and risk factors was conducted. There was a year-on-year increase in the number of infections from 2008 (183) through 2016 (1243). Then, in 2017, the number of infections declined (to 912). As reported previously, HEV G3 group 2 (also known as "G3 abcdhij") is the predominant cause of acute infections, and older men are most at risk. Consumption of pork and pork products was significantly higher among patients than in the general population, but other previously reported associations, such as consumption of shellfish, were not observed. Ongoing surveillance is required to monitor future trends and changes in the epidemiology of the virus. The changing methods of animal husbandry and processing and distribution of animal products needs to be further investigated.

Seroprevalence of Hepatitis E Virus Infection Among People Living With HIV in the Central African Republic.

BackgroundHepatitis E virus (HEV) is a waterborne virus that causes acute hepatitis in immunocompromised patients and those who are immunocompetent. Few cases of chronic HEV have been described in industrialized countries. The Central African Republic is 1 of the few countries in the world that is endemic for both HIV and HEV. The prevalence of HIV infection is estimated to be 4.9% among adults aged 15–49 years, and hepatitis E is epidemo-endemic. The aim of this study was to characterize the epidemiology of HEV infection in people living with HIV (PLHIV) in Bangui.MethodsA cross-sectional study was conducted between April and September 2015 based on answers to a questionnaire, and blood samples were collected for determination of immunological markers by enzyme-linked immunosorbent assay and molecular tests.ResultsOf the 200 PLHIV included, 15 (7.5%) had the IgM that characterizes acute HEV infection; 8.9% were women, and 2.2% were men. The overall seroprevalence of IgG was 68% (48% women and 70.4% men), indicating that men are statistically significantly more exposed to HEV than women. HEV infection had no effect on transaminase or T-CD4+ lymphocyte cell levels. The origin of infection could not be identified.ConclusionsThe seroprevalence of HEV is very high among PLHIV and in the general population of Bangui. This must be taken into account in studies of the risk factors of PLHIV infected with HEV.

Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E Variants.

Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. Zoonotic HEV is an important cause of chronic hepatitis in immunocompromised patients. The rapid identification of novel HEV variants and accumulating sequence information has prompted significant changes in taxonomy of the family Hepeviridae. This family includes two genera: Orthohepevirus, which infects terrestrial vertebrates, and Piscihepevirus, which infects fish. Within Orthohepevirus, there are four species, A–D, with widely differing host range. Orthohepevirus A contains the HEV variants infecting humans and its significance continues to expand with new clinical information. We now recognize eight genotypes within Orthohepevirus A: HEV1 and HEV2, restricted to humans; HEV3, which circulates among humans, swine, rabbits, deer and mongooses; HEV4, which circulates between humans and swine; HEV5 and HEV6, which are found in wild boars; and HEV7 and HEV8, which were recently identified in dromedary and Bactrian camels, respectively. HEV7 is an example of a novel genotype that was found to have significance to human health shortly after discovery. In this review, we summarize recent developments in HEV molecular taxonomy, epidemiology and evolution and describe the discovery of novel camel HEV genotypes as an illustrative example of the changes in this field.

HSV-induced hepatitis in pregnancy - A rare case report

Hepatitis is mostly occurred by alcohol, drugs, or virus. Herpes simplex virus (HSV) hepatitis is rare and accounts for only 1% of all acute liver failures, but it is a fatal complication. Pregnant women are more vulnerable as the immunological changes during pregnancy suppress T-cell-mediated immunity promoting disseminated infection. Although HSV-associated hepatic failure carries a high-mortality risk, early intervention with acyclovir may prove to be life-saving. Here in, we report a case of 22-year-old female 8 weeks primigravida admitted with complaints of yellowish discoloration of eyes and urine and was provisionally diagnosed to have acute severe hepatitis with no hepatic encephalopathy or liver failure. Immunoglobulin M HSV test was positive, suggestive of HSV-induced hepatitis. Due to severe hepatic failure, living donor liver transplantation (left lobe with middle hepatic vein) was performed. She was treated with antivirals, immunosuppressants, and other conservative treatments. After few days her general condition was good, and laboratory investigations were stable. She was shifted out from intensive care unit. At the time of discharge, she was comfortable, vitals stable and wound was healthy. It should be considered in the differential diagnosis of any case of severe hepatitis with concomitant fever, abdominal pain, and elevated values of liver function tests with or without jaundice. The administration of intravenous acyclovir is inexpensive, without drug interactions, and safe even during pregnancy. Clinicians should be aware of HSV-induced hepatitis in immunocompromised patients and its risk factors.

Herpes Hepatitis Causing Fulminant Liver Failure in a Crohnʼs Disease Patient

A 24-year old non pregnant white woman with history of Crohn's disease, started on azathioprine and mesalamine, one month prior to admission, presented with a five day history of fever, chills, diarrhea and abdominal pain. Her physical examination revealed temperature of 102.4 F, abdominal distension and epigastric tenderness. Initial labs showed normal CBC, Klebsiella pneumoniae positive urine culture, ALT 104 units/L (U/L), AST 120 U/L, and normal amylase and lipase levels. She was started on levofloxacin for UTI, and methyl prednisone and metronidazole for possible Crohn's flare. On day 2 of hospitalization, she developed vesiculopapular rash on her chest and abdomen which later spread to her extremities. Her ALT and AST increased to 1401 U/L and 2386 U/L respectively. Hepatitis A IgM, hepatitis B surface antigen, hepatitis core IgM antibody, hepatitis C antibody, ANA, chlamydia/gonococcal PCR test, ASMA, AMA and EBV serology were negative. Imaging studies including RUQ ultrasound, CT scan of abdomen/pelvis, and HIDA scan were normal. Her condition declined with fulminant hepatitis, coagulopathy, and pancytopenia. She admitted to having unprotected sex and contracting herpes simplex virus (HSV) in the past. She was empirically started on intravenous acyclovir and subsequently found positive for HSV type 2 IgM antibodies with titer >1:160. Acyclovir was continued for 14 days with near complete normalization of liver enzymes, coagulation studies, and blood counts. HSV viral load decreased from 500 million to 158,000 in 3 weeks. She was discharged on lifelong maintenance dose of acyclovir. HSV is a rare cause of fulminant hepatitis and at risk individuals include neonates, pregnant women, patients like those on steroids, immunosuppressant medications and HIV and cancer patients. Clinical features include fever, nausea, vomiting, abdominal pain, leukopenia, and coagulopathy with or without mucocutaneous lesions. Serum HSV PCR is the diagnostic modality of choice, although liver biopsy remains the gold standard. When HSV hepatitis is suspected or diagnosed, acyclovir should be empirically started, since delay in initiation of antiviral therapy leads to rapid development of sequelae and poor outcomes. To our knowledge, this is the second reported case of HSV hepatitis in a Crohn's disease patient. Hence, HSV hepatitis should be considered in the differential diagnosis of fulminant hepatitis in immunocompromised patients.

Unusual Presentation of Disseminated Histoplasmosis

Histoplasma capsulatum is the most common endemic mycosis in the United States and in rare cases, it could progress to disseminated histoplasmosis in immunocompromised patients. Hepatic manifestations as the primary presenting symptom are uncommon. Fever is the most common symptom in disseminated histoplasmosis, and gastrointestinal symptoms have been reported to be rare, which makes it a diagnostic challenge. We present a 61-year-old female with past medical history of rheumatoid arthritis who had been treated with Plaquenil in the past, presented with abdominal pain, jaundice, fever, chills and poor appetite. Vitals were remarkable for blood pressure of 129/63 mmhg, pulse of 111 beats per minute, temperature of 102.2 °F (oral), respiratory rate of 19 breaths per minute. Physical examination was remarkable for sclera icterus, right upper quadrant abdominal tenderness and jaundice. Her LFTs peaked at AST of 449 U/L, ALT of 745 U/L, ALP of 1045 U/L, total bilirubin of 11.6 mg/dL with direct bilirubin of 2.4 mg/dL, and GGT of 620 U/L. Negative work up included HAV, HBV, HCV, ANA, AMA, ASMA, ANCA, LKM, CMV IgM, EBV IgM, and HIV. APAP, Salicylate, CA 19-9 and CEA levels were within normal range. Abdominal ultrasound was unremarkable. CT and MRI abdomen were remarkable for mild splenomegaly. Patient was started on Vancomycin and Zosyn due to her septic picture, but symptoms did not improve. After few days blood cultures started growing Histoplasmosis Capsulatum, the histoplasma antigen was positive as well. Patient was started on Amophotericin B and Voriconazole and discharged home on Itraconzaole. Follow up appointment 2 months later showed improved LFTs and significant improvement in symptoms, with resolution of her jaundice. Disseminated histoplasmosis in our patient presented with hepatocellular jaundice and was diagnosed with acute hepatitis. Early diagnosis of disseminated histoplasmosis should be made by histoplasma antigen detection in urine and serum. In severe cases, Amphotericin B should be used initially and then it could be switched to Itraconazole due to the more desirable side effect profile. Once symptoms resolve and antigen levels return to normal, treatment can be discontinued. Prospective studies are needed to accurately assess the risk of fungal infections presenting like hepatitis in immunocompromised patients. Hence, clinicians should have a high index of suspicion for disseminated histoplasmosis in immunocompromised patients.

Herpes Simplex Virus Hepatitis Treated with Acyclovir

Herpes simplex viruses (HSVs) are the most common cause of mucocutaneous infections with dissemination to visceral organs. HSV-induced hepatitis is a rare but frequent cause of hepatitis in immunocompromised patients, pregnant women, and newborns. However, diagnosis is often difficult because the clinical features are nonspecific. In addition, the HSV-related mortality rate is high. Signs and symptoms of HSV include fever, anorexia, nausea, vomiting, abdominal pain or tenderness, leukocytopenia, coagulopathy, and an increase in serum transaminase levels without jaundice. We present a patient who did not correspond to the above symptoms, but survived following prompt intravenous high-dose acyclovir provided early in the course of the disease. (Ewha Med J 2016;39(3):81-84)

Investigation of the hepatitis E virus seroprevalence in cases admitted to Hacettepe University Medical Faculty Hospital

Hepatitis E virus (HEV), classified in Hepeviridae family, Hepevirus genus, is a non-enveloped virus with icosahedral capsid containing single-stranded positive sense RNA genome. HEV infections may be asymptomatic especially in children, however it may present as fulminant hepatitis in pregnant women, as well as chronic hepatitis in immunocompromised patients. There are four well-known genotypes of HEV that infect humans and many mammalian species. Genotype 1 and 2 are frequently responsible for water-borne infections transmitted by fecal-oral way in developing countries, while genotype 3 and 4 cause zoonotic infections in developed countries. Turkey is considered as an endemic country with a total seroprevalence rate of 6.3% for normal population, showing significant variation (0-73%) according to the regions and study groups. The aims of this study were to investigate the HEV seropositivity in cases admitted to Hacettepe University Medical Faculty Hospital (HUMFH), to evaluate the results according to the demographic features of patients, and to determine the current HEV seroprevalence in our region, contributing seroepidemiological data in Turkey. A total of 1043 serum samples (514 female, 529 male; age range: 1-90 years, mean age: 38.03) obtained from 327 blood donors (32 female, 295 male; age range: 19-59 years, mean age: 31.1) who were admitted to HUMFH Blood Center, and 716 sera (482 female, 234 male; age range: 1-90 years, mean age: 41.7) that were sent to HUMFH Central Laboratory from various outpatient/inpatient clinics, between November 2012 to November 2013, were included in the study. The presence of HEV-IgG antibodies in serum samples was detected by a commercial ELISA method (Euroimmun, Germany), and the presence of HEV-IgM antibodies was also investigated in the sera with IgG-positive results. The overall HEV-IgG seropositivity rate was determined as 4.4% (46/1043), and the seropositivity rates for blood donors and in/outpatients were as 0.92% (3/327) and 6.0% (43/716), respectively. HEV-IgM antibody was not detected in any of the cases. The HEV-IgG seropositivity was 3.2% among male, and 5.6% among female, yielding no statistically significant difference between the gender (p= 0.056). HEV-IgG antibodies were detected in none (0/118) of the pediatric age group (0-18 years), while the seropositivity rates were 1.9% (14/731) and 16.5% (32/194) in 19-55 and ≥ 56 years-old groups, respectively. The difference between the age groups was statistically significant (p< 0.001), indicating the age-related pattern of HEV exposure. In conclusion, the total HEV seroprevalence rate found as 4.4% in our study, is comparable to the average results reported from Turkey. Our data is also in agreement with the result of a previous report (3.8%) that performed from Ankara province in 2002 with similar study groups, emphasizing that there was no significant changes for HEV exposure have occured over more than the last decade in Ankara, Cental Anatolia, Turkey.

Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin

Infection with hepatitis E virus genotype 3 may result in chronic hepatitis in immunocompromised patients. Reduction of immunosuppression or treatment with ribavirin or pegylated interferon-α can result in viral clearance. However, safer and more effective treatment options are needed. Here, we show that sofosbuvir inhibits the replication of hepatitis E virus genotype 3 both in subgenomic replicon systems as well as a full-length infectious clone. Moreover, the combination of sofosbuvir and ribavirin results in an additive antiviral effect. Sofosbuvir may be considered as an add-on therapy to ribavirin for the treatment of chronic hepatitis E in immunocompromised patients.

LP54 : Sofosbuvir inhibits hepatitis E virus replication in vitro and results in an additive effect when combined with ribavirin

Infection with hepatitis E virus genotype 3 may result in chronic hepatitis in immunocompromised patients. Reduction of immunosuppression or treatment with ribavirin or pegylated interferon-a can result in viral clearance. However, safer and more effective treatment options are needed. Here, we show that sofosbuvir inhibits the replication of hepatitis E virus genotype 3 both in subgenomic replicon systems as well as a full-length infectious clone. Moreover, the combination of sofosbuvir and ribavirin results in an additive antiviral effect. Sofosbuvir may be considered as an add-on therapy to ribavirin for the treatment of chronic hepatitis E in immunocompromised patients.

Genome Sequence of a Hepatitis E Virus of Genotype 3e from a Chronically Infected Kidney Transplant Recipient

Hepatitis E virus (HEV) is an emerging cause of acute and chronic hepatitis in immunocompromised patients in Europe. We report the genome sequence of a genotype 3e HEV from a chronically infected kidney transplant recipient in southeastern France, the second HEV genome sequence from a transplant recipient and the first of subtype 3e.

Occult hepatitis B virus infection.

Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host's strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI.