Hepatitis E virus-induced severe myositis
Authors: Arnaud Del Bello, Marie Christine Arné-Bes, Laurence Lavayssière, Nassim Kamar
Journal: Journal of Hepatology (2012)

Genotype 3 hepatitis E virus (HEV3) infection is responsible for self-limiting acute hepatitis, chronic HEV3 infection leading to cirrhosis in immunosuppressed patients, and several extra-hepatic manifestations, i.e., neurological symptoms, kidney injury, and severe thrombocytopenia [1Kamar N. Bendall R. Legrand-Abravanel F. Xia N.S. Ijaz S. Izopet J. et al.Hepatitis E.Lancet. 2012; 379 (Erratum. Lancet 2012;380:730): 2477-2488Abstract Full Text Full Text PDF PubMed Scopus (748) Google Scholar, 2Fourquet E. Mansuy J.M. Bureau C. Recher C. Vinel J.P. Izopet J. et al.Severe thrombocytopenia associated with acute autochthonous hepatitis E.J Clin Virol. 2010; 48: 73-74Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 3Kamar N. Bendall R.P. Peron J.M. Cintas P. Prudhomme L. Mansuy J.M. et al.Hepatitis E virus and neurologic disorders.Emerg Infect Dis. 2011; 17: 173-179Crossref PubMed Scopus (251) Google Scholar, 4Kamar N. Selves J. Mansuy J.M. Ouezzani L. Peron J.M. Guitard J. et al.Hepatitis E virus and chronic hepatitis in organ-transplant recipients.N Engl J Med. 2008; 358: 811-817Crossref PubMed Scopus (1063) Google Scholar, 5Kamar N. Weclawiack H. Guilbeaud-Frugier C. Legrand-Abravanel F. Cointault O. Ribes D. et al.Hepatitis E virus and the kidney in solid-organ-transplant patients.Transplantation. 2012; 93: 617-623PubMed Google Scholar]. Ribavirin therapy has been shown to be an efficient therapy for chronic HEV infection [6Mallet V. Nicand E. Sultanik P. Chakvetadze C. Tesse S. Thervet E. et al.Brief communication: case reports of ribavirin treatment for chronic hepatitis E.Ann Intern Med. 2010; 153: 85-89Crossref PubMed Scopus (155) Google Scholar, 7Kamar N. Rostaing L. Abravanel F. Garrouste C. Lhomme S. Esposito L. et al.Ribavirin therapy inhibits viral replication in patients with chronic hepatitis E virus infection.Gastroenterology. 2010; 139: 1612-1618Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar]. Herein, we report on a first case of Guillain–Barré syndrome associated with severe necrotizing myositis that occurred in a liver-transplant patient in acute HEV-infection phase, who then recovered after ribavirin therapy. A 65-year-old liver-transplant male presented, 7 years after transplantation for alcoholic liver disease, with an autochthonous acute HEV infection (Fig. 1): jaundice, increased liver-enzyme levels, positive serum HEV RNA (126,000 copies/ml, genotype 3f), and positive anti-HEV IgG and IgM (Wantai Biologic Pharmacy Enterprise, Beijing, People’s Republic of China). All other causes of hepatitis were ruled out. The source of HEV infection has not been clearly identified. However, the patient had eaten undercooked pork meat. He was receiving cyclosporine A (C2 level at 600 ng/ml), mycophenolatemofetil, and steroids. Cyclosporine A doses were dramatically decreased (C2 level at 300 ng/ml). Ten days later, he was unable to stand upright. Neurological examination showed severe quadriparesis, with proximal muscle weakness and abolition of biceps, patellar, and Achilles’ tendon reflexes, as well as a right lower facial palsy. Creatine kinase (CK) level was increased to 191,603 IU/L (normal <170 IU/L). Electrophysiological studies showed signs of peripheral demyelinating polyradiculopathy with abolition or prolongation of F-wave responses and sensory conduction was altered more in upper limbs. At rest, needle electromyography showed diffuse abnormal spontaneous activity in all four limbs. Cerebrospinal-fluid (CSF) analysis showed elevated protein level (0.64 g/L), no leukocytes, and no HEV RNA, whereas serum HEV RNA was still positive (49,600 copies/ml). The CSF to serum-albumin ratio was 12.81. The CSF (IgG:albumin) to serum (IgG:albumin) ratio was 0.47. Cryoglobulinemia, serum anti-ganglioside (GM1, GM-2, GM-3, GM4, GD1A, GD1B, GD2, GD3, GT1A, GD1B, GQ1B) antibodies, anti-myelin-associated glycoprotein antibodies, as well as serum and CSF onconeuronal antibodies, were negative. A biopsy specimen of the left bicep brachial muscle showed myopathic changes, with a significant percentage of necrotic muscle fibers (≈10%) and some inflammatory elements. There was no capillary thickening. The day after admission, he developed acute respiratory failure that required mechanical ventilation. Because of suspected HEV-induced Guillain–Barré syndrome associated with severe myositis, mycophenolatemofetil was withdrawn and the patient was given intravenous immunoglobulins (1 g/kg/d for 2 days) and ribavirin therapy [400 mg/d adapted to his glomerular filtration rate (40 ml/min)]. Rapidly after the initiation of both therapies, CK and ALT levels decreased and returned to within the normal range, respectively, 3 and 30 days later. Serum HEV RNA became undetectable by day 15, but ribavirin therapy was continued for 3 months as initially scheduled. Two months after ribavirin was stopped, serum HEV RNA was still negative. Fifteen days after HEV clearance, progressive recovery of mobility was noted. An electromyograph, performed at 2 months after initiation of ribavirin treatment, i.e., 1.5 months after HEV clearance, showed myopathic changes to weak muscles. Studies on nerve conduction showed stable demyelination and severe sensitivo-motor axonal injury. Unfortunately, due to mechanical ventilation, he developed a pulmonary infection that evolved to septic shock, which was complicated by ischemic necrosis of the cecum. Currently, he continues rehabilitation and is being weaned off mechanical ventilation. HEV-induced Guillain–Barré has been previously reported [[3]Kamar N. Bendall R.P. Peron J.M. Cintas P. Prudhomme L. Mansuy J.M. et al.Hepatitis E virus and neurologic disorders.Emerg Infect Dis. 2011; 17: 173-179Crossref PubMed Scopus (251) Google Scholar]. However, this is the first case of HEV-induced severe myositis. Similar to HCV-induced myositis [[8]Di Muzio A. Bonetti B. Capasso M. Panzeri L. Pizzigallo E. Rizzuto N. et al.Hepatitis C virus infection and myositis: a virus localization study.Neuromuscul Disord. 2003; 13: 68-71Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar], in the present case, Guillain–Barré syndrome and severe myositis seem to be related to an auto-immune response. Interestingly, the use of ribavirin allowed rapid clearance of HEV infection, which may have accelerated the neurological and muscle recovery. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.