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Mishra S, Taneja S. Algorithmic Approach to Deranged Liver Functions After Transplantation. J Clin Exp Hepatol 2024; 14:101317. [PMID: 38264576 PMCID: PMC10801315 DOI: 10.1016/j.jceh.2023.101317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 12/06/2023] [Indexed: 01/25/2024] Open
Abstract
Liver transplant (LT) recipients require close follow-up with regular monitoring of the liver function tests (LFTs). Evaluation of deranged LFT should be individualized depending upon the time since LT, peri-operative events, clinical course, and any complications. These derangements can range from mild and asymptomatic to severe and symptomatic elevations requiring expedited personalized assessment and management. Pattern of LFT derangement (hepatocellular, cholestatic, or mixed), donor-recipient risk factors, timing after LT (post-operative, 1-12 months, and >12 months since LT) along with clinical context and symptomatology are important considerations before proceeding with the initial evaluation. Compliance to immunosuppression and drug interactions should be ascertained along with local epidemiology of infections. Essential initial evaluation must include an ultrasound abdomen with Doppler to rule out any structural causes such as biliary or vascular complications apart from focussed laboratory evaluation. Early allograft dysfunction, ischemia reperfusion injury, small-for-size syndrome, biliary leaks, hepatic artery, and portal vein thrombosis are usual culprits in the early post-operative period whereas viral hepatitis (acute or reactivation), opportunistic infections, and recurrence of the primary disease are more frequent in the later period. Graft rejection, biliary strictures, sepsis, and drug induced liver injury remain possible etiologies at all times points after LT. Initial evaluation algorithm must be customized based on history, clinical examination, risk factors, and pattern and severity of deranged LFT. Allograft rejection is a diagnosis of exclusion and requires liver biopsy to confirm and assess severity. Empirical treatment of rejection sans liver biopsy is discouraged.
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Affiliation(s)
- Saurabh Mishra
- Department of Gastroenterology and Hepatology, Paras Health, Sector 22, Panchkula, Haryana 134109, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India
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2
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Shinde AS, Kapoor D. Infections After Liver Transplant -Timeline, Management and Prevention. J Clin Exp Hepatol 2024; 14:101316. [PMID: 38264574 PMCID: PMC10801311 DOI: 10.1016/j.jceh.2023.101316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 12/06/2023] [Indexed: 01/25/2024] Open
Abstract
Liver transplantation (LT) is the standard treatment for end- stage liver disease. Patient and graft survival have improved significantly in the last three decades owing to improvement in surgical technique, better perioperative management and better immunosuppressive regimens. However, LT recipients are at increased risk of infections, particularly in the first year after transplantation. The risk of infection is directly proportional to immunosuppressive regimen and graft function. In this review, we will briefly discuss the timeline of infections after liver transplant, preventive strategies and management of infectious complications.
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Affiliation(s)
- Ajay S. Shinde
- Consultant Gastroenterologist and Hepatologist, Yashoda Hospitals, Secunderabad, Telangana, India
| | - Dharmesh Kapoor
- Consultant Hepatologist, Yashoda Hospitals, Secunderabad, Telangana, India
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3
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Bansal SB, Ramasubramanian V, Prasad N, Saraf N, Soman R, Makharia G, Varughese S, Sahay M, Deswal V, Jeloka T, Gang S, Sharma A, Rupali P, Shah DS, Jha V, Kotton CN. South Asian Transplant Infectious Disease Guidelines for Solid Organ Transplant Candidates, Recipients, and Donors. Transplantation 2023; 107:1910-1934. [PMID: 36749281 DOI: 10.1097/tp.0000000000004521] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
These guidelines discuss the epidemiology, screening, diagnosis, posttransplant prophylaxis, monitoring, and management of endemic infections in solid organ transplant (SOT) candidates, recipients, and donors in South Asia. The guidelines also provide recommendations for SOT recipients traveling to this region. These guidelines are based on literature review and expert opinion by transplant physicians, surgeons, and infectious diseases specialists, mostly from South Asian countries (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) as well as transplant experts from other countries. These guidelines cover relevant endemic bacterial infections (tuberculosis, leptospirosis, melioidosis, typhoid, scrub typhus), viral infections (hepatitis A, B, C, D, and E; rabies; and the arboviruses including dengue, chikungunya, Zika, Japanese encephalitis), endemic fungal infections (mucormycosis, histoplasmosis, talaromycosis, sporotrichosis), and endemic parasitic infections (malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, strongyloidiasis, and filariasis) as well as travelers' diarrhea and vaccination for SOT candidates and recipients including travelers visiting this region. These guidelines are intended to be an overview of each topic; more detailed reviews are being published as a special supplement in the Indian Journal of Transplantation .
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Affiliation(s)
- Shyam Bihari Bansal
- Department of Nephrology and Kidney Transplantation, Medanta Institute of Kidney and Urology Medanta-Medicity, Gurgaon, India
| | | | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta, Medicity, Gurgaon, India
| | - Rajeev Soman
- Department of Infectious Diseases, Jupiter Hospital, Pune, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Santosh Varughese
- Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Manisha Sahay
- Department of Nephrology, Osmania Medical College, and Hospital, Hyderabad, India
| | - Vikas Deswal
- Department of Infectious Diseases, Medanta, Medicity, Gurgaon, India
| | - Tarun Jeloka
- Department of Infectious Diseases, Jupiter Hospital, Pune, India
| | - Sishir Gang
- Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujrat, India
| | - Ashish Sharma
- Department of Renal Transplant Surgery, PGIMER, Chandigarh, India
| | - Priscilla Rupali
- Department of Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India
| | - Dibya Singh Shah
- Department of Nephrology and Transplant Medicine, Institute of Medicine, Tribhuvan University of Teaching hospital, Kathmandu, Nepal
| | | | - Camille Nelson Kotton
- Transplant and Immunocompromised Host Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Zahmanova G, Takova K, Tonova V, Koynarski T, Lukov LL, Minkov I, Pishmisheva M, Kotsev S, Tsachev I, Baymakova M, Andonov AP. The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development. Viruses 2023; 15:1558. [PMID: 37515244 PMCID: PMC10383931 DOI: 10.3390/v15071558] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.
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Affiliation(s)
- Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Valeria Tonova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Tsvetoslav Koynarski
- Department of Animal Genetics, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Laura L Lukov
- Faculty of Sciences, Brigham Young University-Hawaii, Laie, HI 96762, USA
| | - Ivan Minkov
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Maria Pishmisheva
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Stanislav Kotsev
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, 1606 Sofia, Bulgaria
| | - Anton P Andonov
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
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5
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Songtanin B, Molehin AJ, Brittan K, Manatsathit W, Nugent K. Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations. Viruses 2023; 15:1389. [PMID: 37376687 DOI: 10.3390/v15061389] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
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.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Adebayo J Molehin
- Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Kevin Brittan
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Wuttiporn Manatsathit
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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Markakis GE, Papatheodoridis GV, Cholongitas E. Epidemiology and treatment of hepatitis E in the liver transplantation setting: A literature review. J Viral Hepat 2022; 29:698-718. [PMID: 35644040 DOI: 10.1111/jvh.13709] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 02/01/2022] [Accepted: 05/10/2022] [Indexed: 12/09/2022]
Abstract
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.
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Affiliation(s)
- George E Markakis
- Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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7
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Trongtorsak A, Chaisidhivej N, Yadav K, Kim J, Thongprayoon C, Cheungpasitporn W, Hansrivijit P. Hepatitis E virus infection in hematopoietic stem cell transplant recipients: a systematic review and meta-analysis. J Investig Med 2021; 70:853-858. [PMID: 34930797 DOI: 10.1136/jim-2021-002102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/05/2021] [Indexed: 01/30/2023]
Abstract
Although most patients with hepatitis E virus (HEV) infection are asymptomatic or have mild symptoms, its infection is generally underdiagnosed and overlooked. In immunocompromised patients, HEV infection can lead to acute liver failure and death. However, the clinical evidence of HEV infection in hematopoietic stem cell transplant (HSCT) recipients is scarce; thus, we conducted this systematic review and meta-analysis to assess the prevalence of HEV infection in this population. We searched MEDLINE, EMBASE, and the Cochrane Library databases from inception through October 2020 to identify studies that reported the prevalence of HEV infection among HSCT recipients. HEV infections were confirmed by HEV-IgG/IgM or HEV-RNA assay. A total of 1977 patients from nine studies with a follow-up time up to 40 months were included in the final analysis. The pooled prevalence of positive HEV-RNA was 3.0% (95% CI 2.3% to 4.0%). The pooled prevalence of positive HEV-IgG was 10.3% (95% CI 4.5% to 21.8%). The pooled prevalence of de novo HEV infection was 2.9% (95% CI 1.8% to 4.5%). Age and male gender were not associated with HEV-RNA or HEV-IgG positivity in the meta-regression analysis. In conclusion, the prevalence of HEV-IgG in HSCT recipients was about 10%, while the prevalence of HEV-RNA was only 3%. However, further studies that focus on the clinical outcomes in this population are warranted.
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Affiliation(s)
- Angkawipa Trongtorsak
- Department of Internal Medicine, Amita Health Saint Francis Hospital, Evanston, Illinois, USA
| | - Natapat Chaisidhivej
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA
| | - Kritika Yadav
- Department of Internal Medicine, Amita Health Saint Francis Hospital, Evanston, Illinois, USA
| | - Jinah Kim
- Department of Internal Medicine, UPMC Pinnacle Harrisburg, Harrisburg, Pennsylvania, USA
| | | | | | - Panupong Hansrivijit
- Department of Internal Medicine, UPMC Pinnacle Harrisburg, Harrisburg, Pennsylvania, USA
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Ribeiro da Cunha M, Marques T. A Case of Hepatitis E Persistence in a Patient With Myelofibrosis Under Ruxolitinib. ACG Case Rep J 2021; 8:e00674. [PMID: 34820465 PMCID: PMC8608255 DOI: 10.14309/crj.0000000000000674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 05/07/2021] [Indexed: 11/17/2022] Open
Abstract
Hepatitis E virus (HEV) is a mostly enterically transmitted agent of viral, usually acute hepatitis. In recent years, however, it has been proven to establish chronicity in immunosuppressed patients. We report the first case of HEV infection in a patient with myelofibrosis under ruxolitinib, a tyrosine kinase inhibitor. Although this patient was able to mount a humoral response with specific immunoglobulin G, viral replication could not be controlled until ruxolitinib suspension. After normalization of liver enzymes and clearance of HEV, ruxolitinib was reintroduced with no disease relapse, suggesting spontaneous eradication of the virus.
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Affiliation(s)
- Maria Ribeiro da Cunha
- Department of Infectious Diseases, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Tiago Marques
- Department of Infectious Diseases, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
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Hansrivijit P, Trongtorsak A, Puthenpura MM, Boonpheng B, Thongprayoon C, Wijarnpreecha K, Choudhury A, Kaewput W, Mao SA, Mao MA, Jadlowiec CC, Cheungpasitporn W. Hepatitis E in solid organ transplant recipients: A systematic review and meta-analysis. World J Gastroenterol 2021; 27:1240-1254. [PMID: 33828397 PMCID: PMC8006097 DOI: 10.3748/wjg.v27.i12.1240] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/17/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death. AIM To demonstrate the prevalence of HEV infection in solid organ transplant (SOT) recipients. METHODS We searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through October 2020. The inclusion criteria consisted of adult patients with history of SOT. HEV infection is confirmed by either HEV-immunoglobulin G, HEV-immunoglobulin M, or HEV RNA assay. RESULTS Of 563 citations, a total of 22 studies (n = 4557) were included in this meta-analysis. The pooled estimated prevalence of HEV infection in SOT patients was 20.2% [95% confidence interval (CI): 14.9-26.8]. The pooled estimated prevalence of HEV infection for each organ transplant was as follows: liver (27.2%; 95%CI: 20.0-35.8), kidney (12.8%; 95%CI: 9.3-17.3), heart (12.8%; 95%CI: 9.3-17.3), and lung (5.6%; 95%CI: 1.6-17.9). Comparison across organ transplants demonstrated statistical significance (Q = 16.721, P = 0.002). The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries. The pooled estimated prevalence of de novo HEV infection was 5.1% (95%CI: 2.6-9.6) and the pooled estimated prevalence of acute HEV infection was 4.3% (95%CI: 1.9-9.4). CONCLUSION HEV infection is common in SOT recipients, particularly in middle-income countries. The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants. More studies examining the clinical impacts of HEV infection in SOT recipients, such as graft failure, rejection, and mortality are warranted.
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Affiliation(s)
- Panupong Hansrivijit
- Department of Internal Medicine, UPMC Pinnacle, Harrisburg, PA 17104, United States
| | - Angkawipa Trongtorsak
- Department of Internal Medicine, Amita Health Saint Francis Hospital, Evanston, IL 60202, United States
| | - Max M Puthenpura
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA 19129, United States
| | - Boonphiphop Boonpheng
- David Geffen School of Medicine, University of California, Los Angeles, Division of Nephrology, Los Angeles, CA 90095, United States
| | - Charat Thongprayoon
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Karn Wijarnpreecha
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Jacksonville, FL 32224, United States
| | - Avishek Choudhury
- School of Systems and Enterprises, Stevens Institute of Technology, Hoboken, NJ 07030, United States
| | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
| | - Shennen A Mao
- Department of Transplant Surgery, Mayo Clinic, Jacksonville, FL 32224, United States
| | - Michael A Mao
- Department of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL 32224, United States
| | - Caroline C Jadlowiec
- Department of Transplant Center, Mayo Clinic, Scottsdale, AZ 85259, United States
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Chanmanee T, Ajawatanawong P, Louisirirotchanakul S, Chotiyaputta W, Chainuvati S, Wongprompitak P. Phylogenetic analysis of two new complete genomes of the hepatitis E virus (HEV) genotype 3 from Thailand. Mol Biol Rep 2020; 47:8657-8668. [PMID: 33058031 PMCID: PMC7674359 DOI: 10.1007/s11033-020-05908-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 10/08/2020] [Indexed: 02/06/2023]
Abstract
Hepatitis E virus (HEV) is a causative agent of acute viral hepatitis globally. Evolutionary phylogeny classifies the HEV into eight genotypes that correlate with the viral transmission. Only four genotypes have been proven to be responsible for transmission in humans. However, there has been no report on the genomics and genotyping of HEV in Thailand during the past ten years. Here, we identified the genotype distributions of the Thai isolates of HEV and we sequenced two HEV genomes. We screened for 18 Thai isolates of HEV from Siriraj Hospital in Bangkok, from 2014–2016. The HEV genomes were sequenced from the serum and feces of a patient. The results showed that all Thai isolates of HEV were identified as genotype 3 (HEV-3). The ORF2 and genome phylogenies suggested two subgenotypes, called 3.1 and 3.2. The Thai isolates of HEV were frequently found in the subgenotype 3.1. The genome sequences of the two Thai isolates of HEV from the serum and fecal samples of the same patient showed 91% nucleotide similarity with the HEV genotype 3. Comparisons between the HEV genome and the ORF2 phylogenies illustrated that the ORF2 tree can be used to identify HEV genotypes, but it has less phylogenetic power for the HEV evolution. The two new genome sequences of HEV-3 from Thailand could contribute valuable information to the HEV genome study. (226 words)
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Affiliation(s)
- Tipsuda Chanmanee
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pravech Ajawatanawong
- Division of Bioinformatics and Data Management for Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Suda Louisirirotchanakul
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Watcharasak Chotiyaputta
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Siwaporn Chainuvati
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Patimaporn Wongprompitak
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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11
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Whitsett M, Feldman DM, Jacobson I. Hepatitis E Virus Infection in the United States: Current Understanding of the Prevalence and Significance in the Liver Transplant Patient Population and Proposed Diagnostic and Treatment Strategies. Liver Transpl 2020; 26:709-717. [PMID: 32061053 DOI: 10.1002/lt.25732] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 01/28/2020] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV), of the family Herpesviridae, is a virus that infects nearly 20 million people per year throughout the world. HEV is most commonly transmitted via the fecal-oral route and has long been described as a virus that afflicts only those in resource-poor countries. However, HEV has been detected in numerous animal carriers, various food sources, and even in human blood products in resource-rich regions of the world. HEV is of importance in the transplant patient population because of its ability to cause chronic viral infection in these patients can lead to graft loss and cirrhosis. In this review, we discuss the current knowledge of HEV as it pertains to the liver transplant patient population and discuss diagnosis and treatment of this infection.
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Affiliation(s)
- Maureen Whitsett
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
| | - David M Feldman
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
| | - Ira Jacobson
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
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12
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Darstein F, Häuser F, Mittler J, Zimmermann A, Lautem A, Hoppe-Lotichius M, Otto G, Lang H, Galle PR, Zimmermann T. Hepatitis E Is a Rare Finding in Liver Transplant Patients With Chronic Elevated Liver Enzymes and Biopsy-Proven Acute Rejection. Transplant Proc 2020; 52:926-931. [PMID: 32139278 DOI: 10.1016/j.transproceed.2020.01.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 11/17/2019] [Accepted: 01/22/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND In past decades, liver transplant (LT) patients were not routinely screened for hepatitis E virus (HEV) infection, and thus it might have been misdiagnosed as an acute rejection episode. Our aim was to analyze a real-world cohort of LT patients who presented with at least 1 episode of biopsy-proven acute rejection (BPAR) and suffered from persistent elevated transaminases, to evaluate the frequency of HEV infection misdiagnosed as a rejection episode. METHODS Data from 306 patients transplanted between 1997 and 2017, including 565 liver biopsies, were analyzed. Biopsies from patients suffering from hepatitis C (n = 79; 25.8%) and from patients who presented with a Rejection Activity Index <5 (n = 134; 43.8%) were excluded. A subgroup of 74 patients (with 134 BPAR) with persistently elevated liver enzymes was chosen for further HEV testing. RESULTS Positive HEV IgG was detectable in 18 of 73 patients (24.7%). Positive HEV RNA was diagnosed in 3 of 73 patients with BPAR (4.1%). Patients with HEV infection showed no difference in etiology of the liver disease, type of immunosuppression, or median Rejection Activity Index. CONCLUSION Few HEV infections were misdiagnosed as acute rejection episodes in this real-world cohort. Thus, HEV infection is an infrequent diagnosis in cases with persistent elevated liver enzymes and BPAR after LT.
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Affiliation(s)
- F Darstein
- First Department of Internal Medicine, Gastroenterology and Hepatology, Universitätsmedizin Mainz, Mainz, Germany.
| | - F Häuser
- Institute for Clinical Chemistry and Laboratory Medicine, Universitätsmedizin Mainz, Mainz, Germany
| | - J Mittler
- Department of Hepatobiliary and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - A Zimmermann
- First Department of Internal Medicine, Gastroenterology and Hepatology, Universitätsmedizin Mainz, Mainz, Germany
| | - A Lautem
- Department of Hepatobiliary and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - M Hoppe-Lotichius
- Department of Hepatobiliary and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - G Otto
- Department of Hepatobiliary and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - H Lang
- Department of Hepatobiliary and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - P R Galle
- First Department of Internal Medicine, Gastroenterology and Hepatology, Universitätsmedizin Mainz, Mainz, Germany
| | - T Zimmermann
- First Department of Internal Medicine, Gastroenterology and Hepatology, Universitätsmedizin Mainz, Mainz, Germany
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Millson C, Considine A, Cramp ME, Holt A, Hubscher S, Hutchinson J, Jones K, Leithead J, Masson S, Menon K, Mirza D, Neuberger J, Prasad R, Pratt A, Prentice W, Shepherd L, Simpson K, Thorburn D, Westbrook R, Tripathi D. Adult liver transplantation: UK clinical guideline - part 2: surgery and post-operation. Frontline Gastroenterol 2020; 11:385-396. [PMID: 32879722 PMCID: PMC7447281 DOI: 10.1136/flgastro-2019-101216] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 09/01/2019] [Accepted: 09/30/2019] [Indexed: 02/06/2023] Open
Abstract
Survival rates for patients following liver transplantation exceed 90% at 12 months and approach 70% at 10 years. Part 1 of this guideline has dealt with all aspects of liver transplantation up to the point of placement on the waiting list. Part 2 explains the organ allocation process, organ donation and organ type and how this influences the choice of recipient. After organ allocation, the transplant surgery and the critical early post-operative period are, of necessity, confined to the liver transplant unit. However, patients will eventually return to their referring secondary care centre with a requirement for ongoing supervision. Part 2 of this guideline concerns three key areas of post liver transplantation care for the non-transplant specialist: (1) overseeing immunosuppression, including interactions and adherence; (2) the transplanted organ and how to initiate investigation of organ dysfunction; and (3) careful oversight of other organ systems, including optimising renal function, cardiovascular health and the psychosocial impact. The crucial significance of this holistic approach becomes more obvious as time passes from the transplant, when patients should expect the responsibility for managing the increasing number of non-liver consequences to lie with primary and secondary care.
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Affiliation(s)
- Charles Millson
- Department of Hepatology, York Teaching Hospitals NHS Foundation Trust, York, UK
| | - Aisling Considine
- Pharmacy department, King's College Hospital NHS Foundation Trust, London, UK
| | - Matthew E Cramp
- South West Liver Unit, Plymouth Hospitals NHS Trust, Plymouth, UK
| | - Andrew Holt
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Stefan Hubscher
- Department of Cellular Pathology, University of Birmingham, Birmingham, UK
| | - John Hutchinson
- Department of Hepatology, York Teaching Hospitals NHS Foundation Trust, York, UK
| | - Kate Jones
- Liver Transplantation Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Joanna Leithead
- Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Steven Masson
- Liver Unit, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Krish Menon
- Liver Transplantation & HPB Surgery, King’s College Hospital NHS Foundation Trust, London, UK
| | - Darius Mirza
- Liver Transplantation & HPB surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - James Neuberger
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Raj Prasad
- Liver Transplantation & HPB Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Anthony Pratt
- Pharmacy Department, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Wendy Prentice
- Palliative Care Medicine, King’s College Hospital NHS Foundation Trust, London, UK
| | - Liz Shepherd
- Liver Transplantation Service, Royal Free London NHS Foundation Trust, London, UK
| | - Ken Simpson
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Doug Thorburn
- Department of Hepatology, Royal Free London NHS Foundation Trust, London, UK
| | - Rachel Westbrook
- Department of Hepatology, Royal Free London NHS Foundation Trust, London, UK
| | - Dhiraj Tripathi
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birminghams, UK
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14
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Hoad VC, Gibbs T, Ravikumara M, Nash M, Levy A, Tracy SL, Mews C, Perkowska-Guse Z, Faddy HM, Bowden S. First confirmed case of transfusion-transmitted hepatitis E in Australia. Med J Aust 2018; 206:289-290. [PMID: 28403756 DOI: 10.5694/mja16.01090] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 01/03/2017] [Indexed: 01/02/2023]
Affiliation(s)
| | | | | | - Monica Nash
- Australian Red Cross Blood Service, Sydney, NSW
| | - Avram Levy
- PathWest Laboratory Medicine WA, Perth, WA
| | - Samantha L Tracy
- Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC
| | | | | | | | - Scott Bowden
- Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC
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15
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Serological and virological survey of hepatitis E virus (HEV) in animal reservoirs from Uruguay reveals elevated prevalences and a very close phylogenetic relationship between swine and human strains. Vet Microbiol 2018; 213:21-27. [DOI: 10.1016/j.vetmic.2017.11.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 11/12/2017] [Accepted: 11/13/2017] [Indexed: 02/07/2023]
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16
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García-Hernández ME, Cruz-Rivera M, Sánchez-Betancourt JI, Rico-Chávez O, Vergara-Castañeda A, Trujillo ME, Sarmiento-Silva RE. Seroprevalence of anti-hepatitis E virus antibodies in domestic pigs in Mexico. BMC Vet Res 2017; 13:289. [PMID: 28934965 PMCID: PMC5609016 DOI: 10.1186/s12917-017-1208-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 09/14/2017] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) infection is one of the most common causes of acute liver diseases in humans worldwide. In developing countries, HEV is commonly associated with waterborne outbreaks. Conversely, in industrialized countries, HEV infection is often associated with travel to endemic regions or ingestion of contaminated animal products. Limited information on both, human and animal HEV infection in Mexico is available. As a consequence, the distribution of the virus in the country is largely unknown. Here, we assessed the seroprevalence of HEV among swine in different geographical regions in Mexico. METHODS Seroprevalence of anti-HEV antibodies in swine herds in Mexico was evaluated in a representative sample including 945 pig serum specimens from different regions of the country using a commercial enzyme-linked immunosorbent assay (ELISA). RESULTS The overall prevalence of anti-HEV antibodies in swine was 59.4%. The northern region of Mexico exhibited the highest seroprevalence in the country (86.6%), while the central and southern regions in Mexico showed lower seroprevalence, 42.7% and 51.5%, respectively. CONCLUSIONS In Mexico, HEV seroprevalence in swine is high. Importantly, northern Mexico showed the highest seroprevalence in the country. Thus, further studies are required to identify the risk factors contributing to HEV transmission among pigs in the country. Assessment of HEV human infection in the context of viral transmission in swine is required to better understand the epidemiology of hepatitis E in Mexico.
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Affiliation(s)
| | - Mayra Cruz-Rivera
- Facultad de Medicina, Universidad Nacional Autónoma de México, 04510, Ciudad de México, México
| | - José Iván Sánchez-Betancourt
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, 04510, México
| | - Oscar Rico-Chávez
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, 04510, México
| | - Arely Vergara-Castañeda
- Facultad de Ciencias Químicas, Universidad La Salle, Benjamín Franklin 47, 06140, Ciudad de México, México
| | - María E Trujillo
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, 04510, México
| | - Rosa Elena Sarmiento-Silva
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, 04510, México.
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17
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Yin X, Li X, Feng Z. Role of Envelopment in the HEV Life Cycle. Viruses 2016; 8:v8080229. [PMID: 27548201 PMCID: PMC4997591 DOI: 10.3390/v8080229] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/02/2016] [Accepted: 08/11/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatitis E virus (HEV), an enterically transmitted hepatotropic virus, was thought to be non-enveloped for decades. However, recent studies have revealed that the virus circulating in the patient’s blood is completely cloaked in host membranes and resistant to neutralizing antibodies. The discovery of this novel enveloped form of HEV has raised a series of questions about the fundamental biology of HEV and the way this virus, which has been understudied in the past, interacts with its host. Here, we review recent advances towards understanding this phenomenon and discuss its potential impact on various aspects of the HEV life cycle and immunity.
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Affiliation(s)
- Xin Yin
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
| | - Xinlei Li
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
| | - Zongdi Feng
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43205, USA.
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