Chronic Hepatitis E Virus Infection Research Articles

Mini Review] Global Burden and Evolving Understanding of Hepatitis E Virus

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide, recognized as a significant global public health concern. Recent advancements in understanding the natural history of HEV infection have shed light on its epidemiology and clinical implications. The primary mode of HEV transmission is fecal-oral, occurring through contaminated water or food. Parenteral transmission, particularly through blood transfusions, was initially overlooked but has been increasingly recognized in both developing and industrialized countries. Acute HEV infection typically manifests as self-limiting jaundice, particularly in immunocompetent individuals. However, recent data suggest that acute infection can progress to a chronic form in various immunosuppressive conditions, including solid organ transplantation, hematological malignancies, and human immunodeficiency virus (HIV) infection. Chronic HEV can lead to cirrhosis, which may progress rapidly in some cases. Extrahepatic manifestations, particularly neurological complications, have also been reported. HEV remains underdiagnosed globally due to a lack of awareness among healthcare providers in many regions. Advances in serological and molecular assays have facilitated reliable diagnosis, both in immunocompetent and immunocompromised patients. Ribavirin monotherapy has proven effective in treating chronic HEV infection in immunosuppressed individuals and is currently widely recommended. However, its efficacy in acute HEV remains inconclusive. In 2011, an effective and well-tolerated HEV vaccine was developed and approved in China. This vaccine holds promise for high-risk populations, particularly individuals with cirrhosis and travelers to endemic regions.

Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients

ObjectivesIn high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to...

Hepatitis E virus infects human testicular tissue and Sertoli cells

Globally, hepatitis E virus (HEV) infections are prevalent. The finding of high viral loads and persistent viral shedding in ejaculate suggests that HEV replicates within the human male genital tract, but its target organ is unknown and appropriate models are lacking. We aimed to determine the HEV tropism in human testis and its potential influence on male reproductive health. We conducted ex vivo culture of human testis explants and in vitro culture of primary human Sertoli cells. Clinically derived HEV genotype 1 (HEV1) and HEV3 virions, as well as rat derived HEV-C1, were used for inoculation. Transcriptomic analysis was performed on testis tissues collected from tacrolimus-treated rabbits with chronic HEV3 infection. Our findings reveal that HEV3, but not HEV1 or HEV-C1, can replicate in human testis explants and primary human Sertoli cells. Tacrolimus treatment significantly enhanced the replication efficiency of HEV3 in testis explants and enabled successful HEV1 infection in Sertoli cells. HEV3 infection disrupted the secretion of several soluble factors and altered the cytokine microenvironment within primary human Sertoli cells. Finally, intratesticular transcriptomic analysis of immunocompromised rabbits with chronic HEV infection indicated a downregulation of genes associated with spermatogenesis. HEV can infect the human testicular tissues and Sertoli cells, with increased replication efficiency when exposed to tacrolimus treatment. These findings shed light on how HEV may persist in ejaculate of patients with chronic hepatitis E and provide valuable ex vivo tool for studying countermeasures.

Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review.

Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus that belongs to Hepeviridae family. HEV is the most common cause of acute viral hepatitis worldwide. According to the World Health Organization (WHO), there are estimated 20 million HEV infections worldwide every year, leading to estimated 3.3 million symptomatic cases of HEV infection. The WHO estimates that HEV infection caused approximately 44,000 deaths in 2015, which represents 3.3% of mortality rates due to viral hepatitis. In low-income (LI) countries and lower-middle-income (LMI) countries, HEV is a waterborne infection induced by HEV genotype (gt) 1 and HEV gt 2 that cause large outbreaks and affect young individuals with a high mortality rate in pregnant women from South Asian countries and patients with liver diseases. HEV gt 3, HEV gt 4, and HEV gt 7 are responsible for sporadic infections with zoonotic transmission mainly through the consumption of raw or undercooked meat from different animals. Acute HEV infection is relatively asymptomatic or mild clinical form, in rare cases the disease can be moderate/severe clinical forms and result in fulminant hepatitis or acute liver failure (ALF). Furthermore, HEV infection is associated with extrahepatic manifestations, including renal and neurological clinical signs and symptoms. Pregnant women, infants, older people, immunocompromised individuals, patients with comorbidities, and workers who come into close contact with HEV-infected animals are recognized as major risk groups for severe clinical form of HEV infection and fatal outcome. Chronic HEV infection can occur in immunocompromised individuals with the possibility of progression to cirrhosis.

MTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels)

BackgroundChronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. Patients and methodsCHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. ResultsThree hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. ConclusionsDespite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

Hepatitis E virus (HEV) infection can cause severe complications and high mortality, particularly in pregnant women, organ transplant recipients, individuals with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating chronic HEV infections. Herein, we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds. Upon screening, we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities. Vidofludimus calcium is the next-generation dihydroorotate dehydrogenase (DHODH) inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 infection. Pyrazofurin selectively targets uridine monophosphate synthetase (UMPS). Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV strains. Encouragingly, both drugs exhibited a sizeable therapeutic window against HEV. For instance, the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in patients. Mechanistically, their anti-HEV mode of action depends on the blockage of pyrimidine synthesis. Notably, two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants (Y1320H, G1634R). Their combination with IFN-α resulted in synergistic antiviral activity. In conclusion, we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV infections. Based on their antiviral potency, and also the favorable safety profile identified in clinical studies, our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

Prevalence and the impact of hepatitis E infection in pediatric liver transplanted recipients with hepatitis in Thailand.

The hepatitis E virus (HEV) infection typically causes acute and self-limiting hepatitis. However, chronic infection can occur in immunocompromised hosts. This study determined the prevalence and impact of HEV infection in liver transplanted (LT) children who had transaminitis. The demographic data, anti-HEV IgM/IgG, serum/stool HEV RNA, and management for LT children with acute or persistent transaminitis from 2003 to 2020 were retrospectively reviewed. HEV serology was tested by ELISA, and HEV RNA was detected by semi-nested PCR. Seventy-two children with LT with persistent transaminitis with a median age of 4.41 (1.32, 9.14) years (55.6% female) and one with acute hepatitis were investigated for HEV infection. Anti-HEV IgM, anti-HEV IgG, serum, or stool HEV RNA was investigated in 95.8% (N = 69), 93.1% (N = 67), 43.1% (N = 31), and 37.5% (N = 27) of patients, respectively. The prevalence of HEV infection was 37.5% (N = 27). There was no significant difference in characteristics between the HEV-infected and HEV-non-infected patients. Moreover, 22.2% (N = 16) and 15.3% (N = 11) of patients had past HEV infection and HEV-related acute or chronic infection, respectively. Most of the patients had primary treatment as the presumed graft rejection without improvement. In two patients, detectable HEV RNA in serum turned undetectable in approximately 2 weeks and 2 months, and liver enzyme levels normalized after reducing immunosuppressive therapy. The prevalence of HEV infection among pediatric LT recipients with hepatitis was high. Chronic HEV infection was evidenced in two patients. Investigations of HEV infection in pediatric LT recipients with persistent transaminitis should guide proper management.

Impact of Hepatitis E Virus Screening in the UK Deceased Organ Donor Population.

Universal Hepatitis E Virus (HEV) screening of deceased organ donors was implemented by the UK national organ procurement organisation in October 2017. Donor testing for HEV infection is done post-transplant; detection of HEV ribonucleic acid (RNA) in donor plasma is therefore not a contra-indication for organ donation, with the result being used to inform recipient management. Immediate post-transplant detection of donor HEV viraemia triggers notification to transplant centres. Follow up of liver and kidney recipients has shown that transmission through solid organs is very efficient, particularly through liver grafts, as expected; no other organ types were transplanted in this cohort. Although donors with higher plasma viral load (VL > 103IU/mL) were invariably associated with recipient infection, transmission was also documented at lower VL levels. Knowledge of donor HEV status has led to identification of transmission of infection via solid organ grafts followed by close patient monitoring and informed clinical management decisions. The purpose of this strategy is to allow early detection of infection and recurrence and treatment to circumvent the risk of accelerated liver damage from chronic HEV infection due to undiagnosed, inadvertent donor-derived transmission of infection.

Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Variable Outcomes of Hepatitis E Infections in Patients with Hemato-Oncologic Diseases

Introduction: The hepatitis E virus (HEV) represents an important cause of viral hepatitis and could cause chronic infections in immunocompromised patients. However, data about immunocompromised patients other than solid organ transplant recipients are limited. Methods: We identified patients from a laboratory database and retrospectively compiled and analyzed clinical as well as laboratory data in detail. Results: Overall, 22 severely immunosuppressed patients, excluding solid organ transplant recipients, were identified. Four patients did not experience viral clearance (one without and three despite ribavirin therapy). Three patients acquired the infection after allogeneic hematopoietic stem cell transplantation (alloHSCT) and recovered spontaneously, whereas another patient, infected prior to alloHSCT, developed a chronic infection. Four patients failed to clear HEV, resulting in fatal liver failure in 2 patients. The CD4+ cell counts increased in all but 1 patient attaining a sustained virological response (SVR), as compared to patients with clinical failure. Severe immunoglobulin deficiency did not appear to obviate the control of HEV. Six of ten (60%) patients with and nine of 12 (75%) patients without ribavirin therapy achieved an SVR. Conclusions: Upfront ribavirin therapy does not appear mandatory in patients without CD4+ lymphopenia, but a prolonged HEV replication carries the risk of liver failure. Our data suggest that chronic HEV infections could cause T-cell exhaustion, which might be overruled with ribavirin therapy.

Hepatitis E virus: has anything changed?

Infection with hepatitis E virus (HEV) is a global health concern, yet a clinically underdiagnosed cause of acute and chronic hepatitis. The WHO estimates that 20 million people are infected with HEV annually, yet the epidemiology, diagnosis and prevention remain elusive in many clinical settings. Orthohepevirus A (HEV-A) genotypes 1 and 2 cause acute, self-limited hepatitis through faecal-oral transmission. In 2022, the first-ever vaccine campaign was implemented as a response to an HEV outbreak in an endemic region. HEV-A genotypes 3 and 4 are zoonotic infections that primarily cause chronic HEV infection in immunosuppressed populations. Pregnant women and immunocompromised persons are at high risk for severe illness in some settings. Another recent advance in our knowledge of HEV is the zoonotic transmission of Orthohepevirus C (HEV-C) to humans, presumably from contact with rodents and/or their excrement. Previously, HEV infection in humans was presumed to be limited to HEV-A only. Clinical recognition and accurate diagnosis are essential to the management of HEV infection and understanding the global burden of the disease. Epidemiology affects clinical presentations. Targeted response strategies in HEV outbreaks are needed for the prevention of disease, and vaccine campaigns may prove to be an effective part of these strategies.

Seroprevalence of hepatitis E virus after pediatric liver transplantation.

Southeast Asia is the endemic area of hepatitis E virus (HEV) infection. We aimed to determine the seroprevalence of the virus, its association, and the prevalence of chronic infection after pediatric liver transplantation (LT). A cross-sectional study was performed in Bangkok, Thailand. Patients aged <18 years who had LT for >2 years underwent serologic and real-time polymerase chain reaction (rt-PCR) tests. Acute HEV infection was defined by the presence of positive anti-HEV immunoglobulin (Ig)M and HEV viremia from the rt-PCR. If the viremia persisted for >6 months, chronic HEV infection was diagnosed. A total of 101 patients had a median age of 8.4 years [interqartile range (IQR): 5.8-11.7]. The seroprevalence of anti-HEV IgG and IgM was 15% and 4%, respectively. Positive IgM and/or IgG were associated with a history of elevated transaminases with an unknown cause after LT (p = 0.04 and p = 0.01, respectively). The presence of HEV IgM was associated with a history of elevated transaminases with an unknown cause within 6 months (p = 0.01). The two patients (2%) diagnosed with chronic HEV infection did not fully respond to the reduction of immunosuppression but responded well to ribavirin treatment. Seroprevalence of HEV among pediatric LT recipients was not rare in Southeast Asia. Since HEV seropositivity was associated with elevated transaminases of an unknown cause, investigation for the virus should be offered in LT children with hepatitis after excluding other etiologies. Pediatric LT recipients with chronic HEV infection may receive a benefit from a specific antiviral treatment.

MTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels)

BackgroundChronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. Patients and methodsCHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. ResultsThree hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. ConclusionsDespite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Integrative Multiomics and Regulatory Network Analyses Uncovers the Role of OAS3, TRAFD1, miR-222-3p, and miR-125b-5p in Hepatitis E Virus Infection.

The hepatitis E virus (HEV) is a long-ignored virus that has spread globally with time. It ranked 6th among the top risk-ranking viruses with high zoonotic spillover potential; thus, considering its viral threats is a pressing priority. The molecular pathophysiology of HEV infection or the underlying cause is limited. Therefore, we incorporated an unbiased, systematic methodology to get insights into the biological heterogeneity associated with the HEV. Our study fetched 93 and 2016 differentially expressed genes (DEGs) from chronic HEV (CHEV) infection in kidney-transplant patients, followed by hub module selection from a weighted gene co-expression network (WGCN). Most of the hub genes identified in this study were associated with interferon (IFN) signaling pathways. Amongst the genes induced by IFNs, the 2'-5'-oligoadenylate synthase 3 (OAS3) protein was upregulated. Protein-protein interaction (PPI) modular, functional enrichment, and feed-forward loop (FFL) analyses led to the identification of two key miRNAs, i.e., miR-222-3p and miR-125b-5p, which showed a strong association with the OAS3 gene and TRAF-type zinc finger domain containing 1 (TRAFD1) transcription factor (TF) based on essential centrality measures. Further experimental studies are required to substantiate the significance of these FFL-associated genes and miRNAs with their respective functions in CHEV. To our knowledge, it is the first time that miR-222-3p has been described as a reference miRNA for use in CHEV sample analyses. In conclusion, our study has enlightened a few budding targets of HEV, which might help us understand the cellular and molecular pathways dysregulated in HEV through various factors. Thus, providing a novel insight into its pathophysiology and progression dynamics.

Ritonavir Blocks Hepatitis E Virus Internalization and Clears Hepatitis E Virus In Vitro with Ribavirin.

Hepatitis E virus (HEV) is increasingly recognized as the leading cause of acute hepatitis. Although HEV infections are mostly self-limiting, a chronic course can develop especially in those with immunocompromised state. Ribavirin is currently used to treat such patients. According to various reports on chronic HEV infections, a sustained virological response (SVR) was achieved in approximately 80% of patients receiving ribavirin monotherapy. To increase the SVR rate, drug combination might be a viable strategy, which we attempted in the current study. Ritonavir was identified in our previous drug screening while searching for candidate novel anti-HEV drugs. It demonstrated potent inhibition of HEV growth in cultured cells. In the present study, ritonavir blocked HEV internalization as shown through time-of-addition and immunofluorescence assays. Its combination with ribavirin significantly increased the efficiency of inhibiting HEV growth compared to that shown by ribavirin monotherapy, even in PLC/PRF/5 cells with robust HEV production, and resulted in viral clearance. Similar efficiency was seen for HEV genotypes 3 and 4, the main causes of chronic infection. The present findings provide insight concerning the advantage of combination therapy using drugs blocking different steps in the HEV life cycle (internalization and RNA replication) as a potential novel treatment strategy for chronic hepatitis E.

Chronic hepatitis E: Advancing research and patient care.

The hepatitis E virus (HEV) was initially thought to exclusively cause acute hepatitis. However, the first diagnosis of chronic hepatitis E in transplant recipients in 2008 profoundly changed our understanding of this pathogen. We have now begun to understand that specific HEV genotypes can cause chronic infection in certain immunocompromised populations. Over the past decade, dedicated clinical and experimental research has substantiated knowledge on the epidemiology, transmission routes, pathophysiological mechanisms, diagnosis, clinical features and treatment of chronic HEV infection. Nevertheless, many gaps and major challenges remain, particularly regarding the translation of knowledge into disease prevention and improvement of clinical outcomes. This article aims to highlight the latest developments in the understanding and management of chronic hepatitis E. More importantly, we attempt to identify major knowledge gaps and discuss strategies for further advancing both research and patient care.

Hepatitis E Virus Infection in Cancer Patients

Hepatitis E virus (HEV) infection in immunocompetent patients can lead to chronic hepatitis and liver failure. However, the burden of HEV infection in cancer patients is largely unknown. We studied the characteristics of HEV infection in patients at a tertiary care cancer center in the United States. This retrospective study included adult cancer patients with HEV infection diagnosed between September 2011 to September 2021. A total of 405 patients were tested for HEV, and 63 (16%) had detectable HEV IgG. Thirty-three patients (52%) were male, 43 were born in America (68%), 46 (73%) were screened for HEV because of pre-existing liver conditions, and 22 (35%) had hematological malignancies. Only 2 patients had detectable HEV RNA. The first patient had myelodysplastic syndrome and underwent allogeneic stem cell transplantation (HSCT). He developed elevated liver enzymes with HEV RNA 14,000 IU/mL (4.2 log IU/mL) 13 months after HSCT. After reducing immunosuppression, his HEV viremia resolved. The second patient had diffuse large B-cell lymphoma and underwent anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. She had elevated liver enzymes with HEV RNA 4,560,000 IU/mL (6.7 log IU/mL) 12 months after CAR T-cell therapy. She developed chronic HEV infection, and ribavirin treatment failed. Now she is being considered for salvage treatment with peginterferon alfa-2a and ribavirin. This study is the first report of chronic HEV infection in patients who received CAR T-cell therapy. HEV infection in cancer patients appears to be at least as common as in the general population. Cancer patients with hematologic malignancies may be at risk for HEV viremia and chronic infection refractory to antiviral treatment.

Characterization of Chronic Hepatitis E Virus Infection in Immunocompetent Rabbits.

Chronic hepatitis E virus (HEV) infection is frequently reported in immunocompromised patients, but has also been increasingly reported in non-immunocompromised individuals. We characterized the course of chronic HEV infection in immunocompetent rabbits. In two independent experiments, 40 specific-pathogen-free rabbits were infected with a rabbit HEV genotype 3 strain in serial diluted titers (108 to 104 copies/mL). Serum and fecal samples were collected weekly and were tested for HEV RNA, antigen, anti-HEV and liver enzymes. Rabbits that spontaneously cleared the infection before 10 weeks post-inoculation (wpi) were kept to the end of the study as recovery control. Liver tissues were collected from HEV-infected rabbits at 5, 10 and 26 wpi for histopathological analysis. Nineteen rabbits (47.5%) developed chronic HEV infection with persistent viraemia and fecal HEV shedding for >6 months. Seroconversion to anti-HEV was observed in 84.2% (16/19) of the chronically infected rabbits. Serum levels of aminotransferase were persistently elevated in most of the rabbits. Characterizations of chronic HEV infection in immunocompetent settings could be recapitulated in rabbits, which can serve as a valuable tool for future studies on pathogenesis.

Epidemiology and treatment of hepatitis E in the liver transplantation setting: A literature review.

Hepatitis E virus (HEV) is a common cause of acute hepatitis in developing countries, but it can also take a chronic course especially in immunocompromised patients. Its epidemiology after liver transplantation (LT) is hard to assess and treatment options are still explored. Between 2009 and 2020, literature reporting HEV prevalence and treatment in LT recipients was searched and a synthesis was attempted. Sixteen studies reported HEV prevalence in consecutive LT patients: HEV RNA positivity ranged between 0%-1.4% and 0%-7.7% for Western and Eastern cohorts, respectively. In studies published between 2009-2014 and 2015-2020, HEV RNA positivity ranged between 0.35%-1.3% (all European) and 0%-7.7% (European: 0%-1.4%), respectively. Five studies evaluated HEV prevalence in LT recipients with abnormal liver enzymes: HEV RNA positivity was 2.9% in studies published between 2009 and 2014 and from 3.5% to 20% in studies published between 2015 and 2020. Twenty-seven studies reported HEV treatment in LT recipients: sustained virologic response was achieved in 15% by immunosuppression reduction alone and in 83% of cases by ribavirin regiments. Chronic HEV infection is affecting LT recipients, mostly those with abnormal liver enzymes and in Eastern countries. HEV diagnoses should be based on PCR techniques. Successful treatment can be achieved with ribavirin in most cases.

Nosocomial transmission of hepatitis E virus and development of chronic infection: The wider impact of COVID-19.

BackgroundTransmission of hepatitis E virus (HEV) within the healthcare setting is extremely rare. Additionally, the development of chronic HEV infection in association with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection and/or its immunomodulatory therapy has not been reported previously.AimsTo describe the investigation and management of a nosocomial HEV transmission incident during the coronavirus disease 2019 (COVID-19) pandemic.MethodsEpidemiological and molecular investigation of two individuals hospitalised with COVID-19 who were both diagnosed with HEV infection.ResultsFindings from our investigation were consistent with transmission of HEV from one patient with a community-acquired HEV infection to another individual (identical HEV sequences were identified in the two patients), most likely due to a breach in infection control practices whilst both patients shared a bed space on the intensive care unit (ICU). Chronic HEV infection requiring treatment with ribavirin developed in one patient with prolonged lymphopaenia attributable to COVID-19 and/or the immunomodulators received for its treatment. Further investigation did not identify transmission of HEV to any other patients or to healthcare workers.ConclusionsThe extraordinary demands that the COVID-19 pandemic has placed on all aspects of healthcare, particularly within ICU settings, has greatly challenged the ability to consistently maintain optimal infection prevention and control practices. Under the significant pressures of the COVID-19 pandemic a highly unusual nosocomial HEV transmission incident occurred complicated further by progression to a chronic HEV infection in one patient.