Guillain–Barré syndrome triggered by acute hepatitis E virus infection: The first reported case from Egypt

Abstract

A man in his early 50 s presented with a 7-day history of progressive, symmetrical weakness that began in the lower limbs and ascended to involve the upper limbs. His symptoms were accompanied by distal paresthesia and complete areflexia. Three weeks prior to presentation, he experienced a self-limiting febrile illness associated with dark urine and elevated transaminase levels, which resolved spontaneously. On admission, laboratory investigations demonstrated elevated liver enzyme levels and positive anti–hepatitis E virus Immunoglobulin M antibodies, confirming acute hepatitis E virus infection. Nerve conduction studies were consistent with the acute inflammatory demyelinating polyneuropathy variant of Guillain–Barré syndrome. The patient was treated with intravenous immunoglobulin (0.4 g/kg/day for 5 days) and was closely monitored for respiratory and autonomic complications. Gradual neurological improvement was observed, along with normalization of liver function tests. To the best our knowledge, this case represents the first documented occurrence of hepatitis E virus-associated Guillain–Barré syndrome in Egypt after a careful review of the literature. It underscores the importance of considering hepatitis E virus infection in the differential diagnosis of Guillain–Barré syndrome, particularly in patients presenting with elevated liver enzymes or a recent history of hepatitis in hepatitis E virus-endemic regions. Early recognition and prompt initiation of immunotherapy may improve neurological recovery and clinical outcomes in this rare but clinically significant association.

Introduction

Guillain–Barré syndrome (GBS) is a rare disorder of the peripheral nervous system characterized by progressive weakness and sensory disturbances, typically occurring after an infection or immunization. ¹ Globally, GBS affects up to 2.7/100,000 person-years across all age groups. ²

Hepatitis E virus (HEV) is one of the most common causes of acute viral hepatitis worldwide. Most HEV infections are asymptomatic. ³ In addition to hepatic manifestations, HEV may present with neurological complications, including GBS, which has been increasingly reported. ⁴

The pathogenesis of HEV-associated GBS remains incompletely understood; however, immune-mediated mechanisms and molecular mimicry have been proposed. ⁵

Diagnosing GBS in the context of HEV infection is challenging because of nonspecific clinical features and the need for serological and molecular confirmation. Furthermore, the high proportion of asymptomatic HEV infections further complicates the diagnosis. Given the growing recognition of this association, HEV infection should be considered in the differential diagnosis and diagnostic evaluation of GBS to ensure timely and appropriate management. Here, we report a rare case of a man in his early 50 s with an unexpected diagnosis of GBS secondary to hepatitis E. This case highlights the importance of considering HEV as a potential cause of neurological manifestations, particularly in patients with GBS.

Case presentation

A man in his early 50s with no significant past medical history presented to the emergency department with a 7-day history of progressive, symmetric weakness in both lower limbs. The weakness began distally and ascended to involve the upper limbs over 48 h. He reported difficulty walking, climbing stairs, and, more recently, handling objects. He also described mild tingling sensations (paresthesia) in his hands and feet but denied bladder or bowel incontinence.

Further history revealed a prodromal illness approximately 3 weeks earlier, characterized by fever, malaise, nausea, and dark-colored urine, which resolved spontaneously after 1 week. He had no recent travel, no history of vaccination within the preceding 6 weeks, and no consumption of raw or undercooked meat.

On physical examination, the patient was afebrile and hemodynamically stable, with intact cranial nerves and normal mental status. Neurological assessment demonstrated symmetrical flaccid paralysis with reduced muscle strength in both the upper and lower limbs (Table 1). Sensory examination revealed diminished light touch and pinprick sensation in a glove-and-stocking distribution. Deep tendon reflexes were absent in all four limbs, and plantar responses were flexor. Abdominal examination revealed mild right upper quadrant tenderness without hepatosplenomegaly. No skin rash or lymphadenopathy was observed.

Table 1.

Neurological examination findings (Medical Research Council scale).

Muscle group	Right side	Left side
Upper limbs
Shoulder abduction	3/5	3/5
Elbow flexion	3/5	3/5
Elbow extension	3/5	3/5
Wrist extension	2/5	2/5
Grip strength	2/5	2/5
Lower limbs
Hip flexion	2/5	2/5
Knee extension	2/5	2/5
Knee flexion	2/5	2/5
Ankle dorsiflexion	0/5	0/5
Ankle plantarflexion	1/5	1/5
Reflexes
Biceps	Absent	Absent
Triceps	Absent	Absent
Brachioradialis	Absent	Absent
Patellar	Absent	Absent
Achilles	Absent	Absent

Initial laboratory investigations (Table 2) were notable for elevated liver transaminases, consistent with recent hepatitis. Serological testing was positive for anti-HEV immunoglobulin M (IgM) and negative for hepatitis A, B, and C, supporting a diagnosis of acute HEV infection. However, HEV RNA PCR testing and HEV genotyping were not available, representing an important diagnostic limitation. Autoimmune hepatitis was considered in the differential diagnosis but was effectively excluded based on the clinical course and available laboratory findings. Other common triggers of GBS, including Campylobacter jejuni, Mycoplasma pneumoniae, and cytomegalovirus, were negative. Antiganglioside antibody testing (anti-GM1 and anti-GD1a) was not performed because it is not routinely available at our center and is not mandatory for the diagnosis of GBS. Lumbar puncture demonstrated classic albuminocytological dissociation, characterized by elevated cerebrospinal fluid (CSF) protein with a normal white blood cell count.

Table 2.

Comprehensive laboratory profile on admission.

Test	Patient value	Reference range
Complete blood count
Hemoglobin (g/dL)	14.2	13.5–17.5
White cell count (×10⁹/L)	9.8	4.0–11.0
Neutrophils (%)	72	40–75
Lymphocytes (%)	22	20–45
Platelets (×10⁹/L)	255	150–400
Liver function tests
Total bilirubin (mg/dL)	2.1	0.2–1.2
Direct bilirubin (mg/dL)	1.5	0.0–0.3
ALT (U/L)	1450	10–40
AST (U/L)	1210	10–40
Alkaline phosphatase (U/L)	185	40–130
Albumin (g/dL)	3.9	3.5–5.0
Renal function and electrolytes
Creatinine (mg/dL)	0.9	0.7–1.3
Sodium (mmol/L)	139	135–145
Potassium (mmol/L)	4.1	3.5–5.0
Inflammatory markers
C-reactive protein (mg/L)	12	<5
CSF analysis
Appearance	Clear and Colorless	Clear and Colorless
Opening pressure (cmH2O)	16	10–20
White cell count (cells/µL)	2	<5
Protein (mg/dL)	95	15–45
Glucose (mg/dL)	70	40–70
Serology and microbiology
Anti-HEV IgM	Positive	Negative
Anti-HEV IgG	Negative	Negative
HBsAg	Negative	Negative
Anti-HAV IgM	Negative	Negative
Anti-HCV	Negative	Negative
Campylobacter jejuni Ab	Negative	Negative
Mycoplasma pneumoniae Ab	Negative	Negative
HIV Ag/Ab combo	Negative	Negative

HEV: hepatitis E virus; HIV: human immunodeficiency virus; ALT: alanine aminotransferase; AST: aspartate aminotransferase; IgM: immunoglobulin M; CSF: cerebrospinal fluid; HAV: hepatitis A virus; HCV: hepatitis C virus; HBsAg: hepatitis B surface antigen.

Nerve conduction studies and electromyography (Table 3) revealed findings consistent with an acute, predominantly demyelinating sensorimotor polyradiculoneuropathy (acute inflammatory demyelinating polyneuropathy variant of GBS) according to the Hadden criteria. The studies showed prolonged distal motor latencies, reduced motor and sensory nerve conduction velocities, partial motor conduction block in the median and peroneal nerves, and absent or delayed F-waves. Electromyography demonstrated reduced recruitment in distal muscles without evidence of active denervation, such as fibrillation potentials or positive sharp waves, supporting the acute phase of the disease.

Table 3.

Nerve conduction study results.

Nerve	Stimulation site	Recording site	DL (m/s)	Amplitude (mV)	CV (m/s)	F-wave latency (m/s)	Comment
Motor NCS
Median R	Wrist	APB	5.8	3.2	38	38	Prolonged DL, slow CV
Median R	Elbow	APB	–	2.9	37	–	Conduction block
Ulnar R	Wrist	ADM	4.2	4.1	42	36	Mildly prolonged DL
Ulnar R	Below elbow	ADM	–	3.8	41	–	Normal
Peroneal R	Ankle	EDB	8.5	0.5	32	Absent	Markedly abnormal
Peroneal R	Fibular head	EDB	–	0.4	31	–	Conduction block
Tibial R	Ankle	AH	7.2	1.2	35	58	Prolonged DL, slow CV
Sensory NCS
Median R	Wrist	Index finger	3.8	15	42	–	Reduced CV
Sural R	Calf	Lateral malleolus	4.5	6	38	–	Reduced amplitude

DL: distal latency; NCS: nerve conduction study; CV: conduction velocity; APB: abductor pollicis brevis; ADM: abductor digiti minimi; EDB: extensor digitorum brevis; AH: abductor hallucis.

MRI of the brain and the entire spinal cord with contrast was unremarkable, excluding other causes of acute myelopathy or radiculopathy, such as transverse myelitis or cord compression. However, lumbar spine MRI showed mild enhancement of the cauda equina nerve roots, a supportive but nonspecific finding in GBS (not shown).

The patient was admitted to the neurology ward for close monitoring of respiratory function, including forced vital capacity (FVC), and for signs of autonomic instability. GBS was diagnosed according to the Brighton criteria and was considered likely secondary to acute HEV infection. He was treated with intravenous immunoglobulin (IVIG) at a dose of 0.4 g/kg/day for 5 days. Supportive management included prophylactic subcutaneous enoxaparin for deep vein thrombosis prevention as well as physiotherapy and occupational therapy.

Liver function was monitored and showed steady improvement (Figure 1), consistent with the self-limiting course of acute HEV infection.

Figure 1.

Trend of liver enzymes and clinical muscle power during hospitalization. Graphical representation showing the rapid normalization of liver transaminases (ALT and AST) contrasted with the slower recovery of muscle strength (MRC sum score) following IVIG administration. This highlights the dissociation between the resolution of the hepatic insult and the neurological immune-mediated process. • Y1-axis: ALT/AST (U/L)—values starting high (e.g. 1450/1210) and trending down steeply. • Y2-axis: MRC sum score (composite score of muscle power, e.g. from 20/60 to 40/60)—values starting low and trending up slowly. • X-axis: hospital day (days 1–14). • Lines: o Line 1 (ALT): steep downward slope. o Line 2 (AST): steep downward slope. o Line 3 (MRC sum score): gradual upward slope, lagging behind the liver recovery. IVIG: intravenous immunoglobulin; MRC: Medical Research Council; ALT: alanine aminotransferase; AST: aspartate aminotransferase.

The patient’s condition stabilized after completion of IVIG (Table 4). He did not require ventilatory support. By day 10, he demonstrated early signs of neurological recovery, with improved strength in the proximal muscle groups (hip flexion improved to 4/5). He was transferred to an inpatient rehabilitation facility on day 14. At 3-month follow-up, he had achieved substantial recovery, was able to ambulate with a cane, and had a Medical Research Council (MRC) sum score of 54/60. Liver function tests had completely normalized.

Table 4.

Clinical course and treatment timeline.

Hospital day	Clinical events	Interventions	Key parameters
Day 1	Admission with ascending paralysis	Neurology consult, baseline labs	MRC: 20/60, FVC: 65%
Day 1–5	IVIG treatment period	IVIG 0.4 g/kg/day	Monitoring for fluid overload
Day 3	NCS/EMG performed	Diagnostic confirmation	AIDP pattern confirmed
Day 5	Completion of IVIG	Supportive care continued	MRC: 24/60, FVC: 72%
Day 7	Initial neurological improvement	Intensive physiotherapy started	MRC: 28/60, FVC: 85%
Day 10	Significant proximal improvement	Ongoing rehabilitation	MRC: 35/60, FVC: 92%
Day 14	Transfer to rehab facility	Discharge from acute care	MRC: 48/60, FVC: 98%
3-month FU	Ambulatory with cane	Outpatient follow-up	MRC: 54/60, Normal FVC

AIDP: acute inflammatory demyelinating polyneuropathy; EMG: electromyography; FVC: forced vital capacity; IVIG: intravenous immunoglobulin; MRC: Medical Research Council sum score (out of 60); NCS: nerve conduction study.

This case was reported according to the clinical Case Report (CARE) guidelines, ⁶ with all patient details deidentified to ensure confidentiality, and the patient provided signed informed consent for publication.

Discussion

GBS is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive, symmetrical limb weakness, areflexia, and variable sensory symptoms. It typically follows an infectious illness, most commonly of respiratory or gastrointestinal origin. Pathogens such as Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus, Epstein–Barr virus, and Zika virus have been implicated in its pathogenesis. ⁷

In recent years, accumulating evidence has supported a potential association between acute HEV infection and GBS, particularly in regions where HEV is endemic. ⁴ Although Egypt is recognized as an HEV-endemic country, neurological complications associated with HEV, such as GBS, have not been previously reported. To the best of our knowledge, this represents the first documented local case. Although GBS remains an uncommon manifestation, it has also been described following other forms of acute viral hepatitis, including hepatitis A, B, C, D, and E. The present case adds to the growing recognition of this rare but clinically significant association between acute HEV infection and GBS and underscores the importance of including HEV serological testing in patients presenting with GBS and concomitant hepatic dysfunction.^8,9

GBS may present with either demyelinating or axonal subtypes. HEV-associated cases have more frequently demonstrated a demyelinating pattern. In contrast, axonal variants of GBS are more commonly associated with pathogens such as Campylobacter jejuni, which induce antibodies against gangliosides concentrated on axonal membranes. ¹⁰

Our patient exhibited the classic features of the acute inflammatory demyelinating polyneuropathy variant of GBS, confirmed by electrophysiological studies demonstrating prolonged distal motor latencies, slowed conduction velocities, and conduction block. CSF analysis revealed albuminocytologic dissociation, further supporting the diagnosis. The temporal relationship between a self-limited hepatitis-like illness and the onset of neurological symptoms within 2–3 weeks, together with positive anti-HEV IgM serology and exclusion of other infectious precipitants, strongly supports HEV infection as the likely immunological trigger.

The pathophysiological mechanism linking HEV and GBS remains incompletely understood; however, two mechanisms have been proposed: direct viral injury due to HEV replication within the nervous system and an indirect immune-mediated process driven by molecular mimicry. ⁴ Molecular mimicry between HEV antigens and peripheral nerve gangliosides may induce an autoimmune response leading to demyelination or axonal injury.^11,12 Several pathogens known to precipitate GBS share similar immunopathogenic mechanisms, suggesting a comparable triggering pathway. ⁵ Campylobacter jejuni represents the classic example: its lipooligosaccharide (LOS) structures mimic neural gangliosides (e.g. GM1 and GD1a), resulting in the production of cross-reactive antiganglioside antibodies that damage peripheral nerves. Specific LOS biosynthesis genes (cst-II, cgtA, and cgtB) are critical for generating these ganglioside-like epitopes. ⁴ Similarly, HEV is thought to induce autoimmunity through molecular mimicry, producing cross-reactive immune responses analogous to those observed in other postinfectious GBS cases. The typical latency of 1–3 weeks between HEV infection and the onset of neurological symptoms parallels that seen with other infectious triggers.^11,12 Collectively, these features—molecular mimicry, cross-reactive immunity, and comparable latency—support a shared mechanism by which HEV may initiate peripheral nerve autoimmunity leading to GBS.

Both HEV genotypes 1 and 3 have been associated with neurological complications, including GBS, neuralgic amyotrophy, and meningoencephalitis. ⁵ Epidemiological studies estimate that neurological manifestations occur in approximately 5–10% of acute HEV infections, with GBS representing the most common peripheral nervous system involvement. ¹³ However, because HEV testing is not routinely performed in patients evaluated for GBS, the true incidence is likely underestimated.

Our patient responded favorably to intravenous immunoglobulin (IVIG), consistent with outcomes reported in previous studies.^4,14 Although hepatic enzyme levels normalized rapidly with resolution of the viral infection, neurological recovery was slower, reflecting the immune-mediated rather than directly neurotoxic nature of GBS. Early initiation of IVIG or plasma exchange remains the mainstay of treatment, and supportive measures—including physiotherapy and respiratory monitoring—are essential for optimal recovery.

The differential diagnosis of acute flaccid paralysis includes transverse myelitis, myasthenia gravis, and polymyositis, among other conditions. In this case, the absence of spinal cord lesions on MRI, normal creatine kinase levels, and neurogenic findings on electromyography helped exclude these alternatives. Importantly, even mild elevations in hepatic enzymes should prompt clinicians to evaluate for viral hepatitis, including HEV, particularly in endemic regions or in the setting of sporadic cases. ⁵

Recognition of HEV as a potential trigger for GBS has important diagnostic and public health implications. HEV infection is frequently underdiagnosed because of its self-limited course and the limited availability of serologic testing. Incorporating HEV screening into the diagnostic evaluation of GBS—especially in patients with elevated liver enzymes—may facilitate earlier identification, guide management, and improve understanding of this association at the population level.^13,14

Conclusion

To the best of our knowledge, this case represents the first documented occurrence of HEV-associated GBS in Egypt based on a careful review of the literature. It reinforces the importance of considering HEV in the differential diagnosis of GBS, particularly in patients presenting with concurrent hepatic abnormalities. Prompt diagnosis and early initiation of IVIG therapy can result in favorable recovery outcomes. Further research and regional surveillance are needed to clarify the prevalence, pathogenesis, and genotype associations of HEV-induced GBS in endemic settings.

Data availability statement

All relevant data supporting the findings of this case report are included within the manuscript. Additional deidentified data are available from the corresponding author on reasonable request.