BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare but serious condition that is refractory to antiepileptic drugs, and current treatment plans are vague. Diagnosis may be difficult without a clear history of cirrhosis. Liver transplantation (LT) is effective to alleviate symptoms, however, there are few reports about LT in the treatment of status epilepticus with HE. To our knowledge, this is the first report of status epilepticus present as initial manifestation of HE. CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalized for generalized tonic-clonic seizures. She reported no history of episodes of HE, stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding. Neurological examination revealed a comatose patient, without papilledema. Laboratory examination suggested liver cirrhosis. Plasma ammonia levels upon admission were five times normal. Brain computed tomography (CT) was normal, while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis and splenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm, consistent with HE, and sharp waves during ictal EEG corresponding to clinical semiology of focal tonic seizures. The symptoms were reversed by continuous antiepileptic treatment and lactulose. She was given oral levetiracetam, and focal aware seizures occasionally affected her 10 mo after LT. CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE, and LT is effective to prevent the relapse.