Hepatitis E virus–associated cryoglobulinemia in solid‐organ–transplant recipients

Marion, Olivier; Abravanel, Florence; Bello, Arnaud Del; Esposito, Laure; Lhomme, Sébastien; Puissant‐Lubrano, Bénédicte; Alric, Laurent; Faguer, Stanislas; Izopet, Jacques; Kamar, Nassim

doi:10.1111/liv.13894

Cited by 35 publications

(35 citation statements)

References 39 publications

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“…Similar mechanisms have previously been shown to be operative in cryoglobulinemia 39 and other extrahepatic complications related to HEV. 40 Unfortunately, in our study, cryoglobulins were not tested, so this hypothesis remains speculative.…”

Section: Discussionmentioning

confidence: 86%

Neurologic complications of acute hepatitis E virus infection

Ripellino

Pasi

Melli

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo assess the prevalence and clinical features of neurologic involvement in patients with acute hepatitis E virus (HEV) infection in Southern Switzerland.MethodsAmong 1,940 consecutive patients investigated for acute hepatitis E, we identified 141 cases of acute of HEV infection (anti-HEV immunoglobulin M and immunoglobulin G both reactive and/or HEV RNA positive) between June 2014 and September 2017. Neurologic cases were followed up for 6 months. We compared patients with and without neurologic symptoms.ResultsNeurologic symptoms occurred in 43 acute HEV cases (30.4%) and consisted of neuralgic amyotrophy (NA, n = 15, 10.6%) and myalgia (n = 28, 19.8%). All NA cases were immunocompetent. Men had higher odds (OR = 5.2, CI 1.12–24.0, p = 0.03) of developing NA after infection with HEV, and in 3 couples simultaneously infected with HEV, only men developed NA. Bilateral involvement of NA was predominant (2:1) and occurred only in men. Seven NA cases were viremic (all genotype 3), but HEV was undetectable in their CSF. In the acute phase of NA, 9 patients were treated with intravenous immunoglobulin and 4 with prednisone, reporting no side effects and improvement in pain and strength. Myalgia occurred both without (n = 16) or with (n = 12) concomitant elevated serum creatinine kinase. Seven cases with myalgia in the shoulder girdle did not have muscle weakness (“forme fruste” of NA).ConclusionsNeurologic symptoms occurred in one-third of acute HEV infections and consisted of NA and myalgia. NA seems to occur more frequently in men infected by HEV and has a predominant (but not exclusive) bilateral involvement.

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Section: Discussionmentioning

confidence: 86%

Neurologic complications of acute hepatitis E virus infection

Ripellino

Pasi

Melli

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“…Among the cardiovascular and hematological manifestations, the commonly reported ones include cryoglobulinemia (n = 51/113; 45.13%) [55] and monoclonal gammopathy (n = 17/113; 15.04%). [24] The cardiovascular manifestations include myocarditis [56,57], cardiac arrhythmias [24], long QT syndrome [58], and Torsade's de pointes [58].…”

Section: Cardiovascular and Hematological Manifestationsmentioning

confidence: 99%

A Systematic Review of the Extra-Hepatic Manifestations of Hepatitis E Virus Infection

et al. 2020

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Hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded RNA icosahedral virus belongs to the genus Orthohepevirus within the Hepeviridae family. HEV infection can be asymptomatic, or it can cause icteric or fulminant hepatitis. Off late, there have been a number of publications reporting the extra-hepatic manifestations of HEV infection, and this systematic review is aimed at summarizing the available evidence in this regard. Two independent investigators searched PubMed, PubMed Central and Embase databases using the search string “(((hepatitis E) AND (Extrahepatic OR Extra-Hepatic))) OR ((Hepatitis E) AND (Neurology OR Cardiology OR Respiratory OR Lung OR Gastrointestinal OR musculoskeletal OR immunology OR pulmonary)) Filters: Abstract availability, English language, and Human studies”. The extra-hepatic manifestations reported in each of the selected articles were classified and reported as neurological, cardiovascular, and hematological and miscellaneous manifestations. The total number of various manifestations reported in our study were n = 324. These include neurological manifestations (n = 178/324 (54.94%)), cardiovascular and hematological manifestations (n = 113/324 (34.88%)), gastro-intestinal/pancreaticobiliary manifestations (n = 24/324 (7.41%)) and other rarer manifestations involving systems such as renal (n = 4/324; 1.24%), endocrine (n = 1/324; 0.31%), dermatology (n = 1/324; 0.31%), respiratory (n = 1/324; 0.31%), muscular (n = 1/324; 0.31%) and immune system (n = 1/324; 0.31%). Thus, HEV can have extra-hepatic manifestations affecting any system of the human body. Further research is needed to elucidate the underlying pathophysiological manifestations of these extra-hepatic manifestations and to prove causal association with HEV.

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“…HEV may also trigger a flare-up of a pre-existing IgA nephropathy [67,70]. HEV RNA has been detected in the cryoprecipitate from the serum of an immunocompetent patient with an acute HEV infection who presented with cryoglobulinemic MPGN [69], and HEV infection was found to be an independent predictive factor for cryoglobulinemia in SOT recipients [71]. Renal function improves after HEV clearance, and proteinuria is reduced in most patients [67,69,70].…”

Section: Renal Manifestationsmentioning

confidence: 99%

Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections

Lhomme

Marion

Abravanel

et al. 2020

JCM

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Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.

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Hepatitis E virus–associated cryoglobulinemia in solid‐organ–transplant recipients

Abstract: In conclusion, a relationship between HEV and cryoglobulin formation seems to exist. However, the clinical impact of cryoglobulinemia in SOT patients infected with HEV has to be confirmed.

Cited by 35 publications

References 39 publications

Neurologic complications of acute hepatitis E virus infection

Neurologic complications of acute hepatitis E virus infection

A Systematic Review of the Extra-Hepatic Manifestations of Hepatitis E Virus Infection

Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections

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