A 65-year-old male patient with a history of cardiovascular risk factors, revascularized ischemic heart disease, and stage 2 sarcoidosis presented with fever, lower back pain, and decreased urine output for three days. He visited the emergency department, where he was initially diagnosed with a urinary tract infection and discharged with oral antibiotic therapy. Due to persistent fever and lack of improvement, he returned to the emergency room three days later. On readmission, laboratory tests revealed hepatitis with elevated transaminases (AST/ALT 183/127U/L), cholestasis (total bilirubin 1.58mg/dL, GGT 285U/L), and a normal prothrombin time. The patient was admitted for further evaluation.
Within the first 48h of hospitalization, he developed intense right shoulder pain accompanied by weakness in the ipsilateral upper limb, which he attributed to prolonged immobility on an emergency department stretcher.
His liver profile worsened, reaching AST/ALT 3074/2735U/L, GGT/ALP 256/127U/L, total bilirubin 7.5mg/dL, and prothrombin time 40%. Consequently, he was transferred to our center for further evaluation and management. On physical examination, the patient was jaundiced but showed no signs of hepatic encephalopathy. Abdominal ultrasound revealed a normal liver structure without focal lesions, no bile duct abnormalities, mild splenomegaly, and no evidence of ascites. Serological tests for hepatitis A (anti-HAV IgM), hepatitis B surface antigen (HBsAg), and hepatitis C virus (anti-HCV) were negative, as were autoantibodies.
A liver biopsy revealed a necroinflammatory pattern without granulomas or infiltrative features. Definitive diagnosis was established by positive anti-hepatitis E virus (HEV) IgM antibodies and detectable HEV RNA. The patient showed progressive clinical and biochemical improvement and was discharged after 17 days of hospitalization with a final diagnosis of severe acute hepatitis E.
At a follow-up visit two weeks later, the patient was asymptomatic with full biochemical resolution of hepatitis. However, he reported residual weakness in his right upper limb and an inability to perform a pincer grip with his hand. At that point, a diagnosis of Parsonage-Turner syndrome (also known as amyotrophic neuralgia or brachial neuritis) was made. After three months, he experienced complete functional recovery.
DiscussionHepatitis E virus (HEV) is an increasingly common cause of acute hepatitis in our region.1 This infection may present with extrahepatic manifestations, including neurological involvement, even in the absence of liver dysfunction.2 A frequently described neurological complication is amyotrophic neuralgia or Parsonage-Turner syndrome.3 This condition is characterized by severe neuropathic pain in the shoulders and arms at onset, followed by weakness, irregular paresis, atrophy, and sensory disturbances. Recovery is slow and, in some cases, incomplete. More than 85% of cases involve bilateral limb involvement.4 In our patient, symptoms were limited to the right upper limb, which could make clinical diagnosis more challenging.
The pathogenesis remains unclear.2 In vitro studies have demonstrated HEV replication in neuronal cells, suggesting possible direct damage. However, indirect or immune-mediated mechanisms, such as cross-reactivity, seem to play a key role, as the condition is more commonly observed in immunocompetent than immunocompromised patients.4
Amyotrophic neuralgia has also been reported following infections with other viruses, including SARS-CoV-2, as well as after vaccinations, trauma, and surgeries. Diagnosis is primarily clinical, but it can be supported by evidence of acute denervation of the brachial plexus on electromyography or magnetic resonance imaging.5
Extrahepatic manifestations, particularly neurological complications such as amyotrophic neuralgia, Guillain-Barré syndrome, and meningoencephalitis, appear to be causally linked to HEV, and with a non-negligible prevalence. While these complications can occur in patients with HEV infection even in the absence of liver involvement, they may also develop in cases of severe hepatitis, as seen in our case. This condition, particularly when unilateral, may go unnoticed unless a thorough clinical history and targeted physical examination are conducted. The abrupt onset, temporal association with acute hepatitis, and detection of HEV infection should shift our diagnostic consideration away from a postural cause. During the acute phase, imaging and electrophysiological studies are often nonspecific, making clinical suspicion essential.5 Our case reinforces the importance of actively assessing for extrahepatic manifestations of HEV, which can sometimes present a diagnostic challenge.
Given that these manifestations may be debilitating and could benefit from specialized management, recognizing them early is essential to prevent diagnostic delays, avoid unnecessary testing, and improve clinical outcomes.
Ethical considerationsAll ethical aspects of the case were managed in accordance with institutional and international guidelines. Patient information was handled with strict confidentiality, anonymized, and included in this publication with appropriate informed consent.
FundingAP has received support from the Rio Hortega program (fellowship CM21/00081) of the Instituto de Salud Carlos III. XF has received support from ISC iiiPI22/00013 and from Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (grant 2021_SGR_01322) and CERCA Programme/Generalitat de Catalunya.
Conflict of interestXF has acted as advisor for Gilead.
