Severe Acute Hepatitis in a COVID‐19 patient: A Case Report

Abstract Liver enzymes abnormalities are one of the reported presentations of coronavirus infection mostly in hospitalized patients. It is important that physicians take all the possible causes of acute hepatitis in consideration when dealing with abnormal liver enzymes in a patient with COVID‐19 infection to reduce the risk of overlooking the underlying disease. Hereby, we reported case of a 39‐year‐Old man who presented with severe acute hepatitis and was infected with COVID‐19, hepatitis A and herpes simplex virus simultaneously.


| CASE PRESENTATION
A 39-year-old man presented with severe myalgia, refusal to eat, headache, fever, fatigue, and weakness over a twoday period. He stated that he had no respiratory symptoms such as chest pain, coughing, sore throat and was not nauseated, vomiting, experiencing diarrhea, or abdominal pain. He also stated that he had no prior underlying conditions. His vital signs were stable during the physical examination, and his oxygen saturation was 96% on room air. A nasopharyngeal swab was performed promptly, and an RT-PCR confirmed COVID-19 infection. A lung CT scan was then performed, which revealed no abnormalities. (Figure 1) He was then treated in an outpatient setting for symptomatic management and supportive care.
He was referred to our hospital a few days later with jaundice, recent darkening of urine, and lightening of stool. His vital signs were stable at the time. His body temperature was 37℃, and his oxygen saturation was 95% on room air. His sclera and skin were unambiguously icteric. No cutaneous manifestations were observed, and cardiac and pulmonary examinations were normal. The abdominal examination revealed hepatomegaly with a liver span of approximately 16 centimeters but no tenderness in the right upper quadrant. Physical examination revealed no additional positive findings.
Additional history taking was conducted regarding jaundice. The patient made no complaints of itchiness, abdominal pain, recent changes in mental status, or insomnia. He disclosed that he had recently camped and drank water from natural springs. He also stated that he was not taking any medication, including herbal compounds, drinking alcohol or injecting drugs, engaging in unprotected sexual activity, or recently being exposed to a jaundiced person. He was not related to anyone with a history of liver disease. Then, preliminary blood tests were performed to determine the presence of jaundice. The following were the findings: serum alanine aminotransferase (ALT) 2228 IU/L, serum aspartate aminotransferase (AST) 1241 IU/L, alkaline phosphatase (ALP) 410, INR 1.4, Albumin 3.4 g/dL, serum total bilirubin 11.2 mg/dL, and serum direct bilirubin 7.2 mg/dL.
He was initially diagnosed with severe acute hepatitis and admitted. Due to the progressive pattern of abnormal liver function and the risk of developing acute liver failure, a liver transplant center was consulted, but he was deemed unsuitable for transplantation due to his infection with COVID-19.
Although elevated liver enzymes are a common manifestation of COVID-19 infection, we performed a thorough work-up to rule out other possible causes of abnormal liver enzymes. Meanwhile, AST and ALT levels rapidly decreased to 186 and 564 IU/L, respectively, but ALP, total and direct bilirubin, and INR levels increased to 663 IU/L, 13.2 mg/dL, 8.4 mg/dL, and 1.64, respectively, on day three of admission. No new symptoms, such as abdominal pain or tenderness, had developed in the patient. An abdominal ultrasound was performed to rule out the presence of cholestasis. Due to the normal ultrasound and the continuing rise in ALP, INR, and bilirubin levels, an MRCP was performed to rule out cholestatic causes. Hepatitis A virus (HAV) antibody IgM and Herpes simplex virus (HSV) were positive in establishing the hepatocellular cause of elevated liver aminotransferase.
Because liver enzymes decreased rapidly while receiving only supportive care, only symptomatic and supportive care was continued, and no other treatment was initiated. ALP, bilirubin, and INR levels all decreased during follow-up, in addition to ALT and AST levels. All liver chemistry studies improved and returned to normal within two months of presentation.

| DISCUSSION
COVID-19 infection manifests itself in various ways, including respiratory symptoms (the most prevalent), cardiac involvement, neurological symptoms, kidney injury, and gastrointestinal symptoms. 3 Another frequently reported symptom of COVID-19 infection is abnormal liver enzyme levels. This symptom has been observed in up to 76% of COVID-19 patients. 5 The majority of reported cases had only a mild elevation of liver enzymes (<2 times ULN), and only 6% of reported cases had severe liver enzyme changes (>5 times ULN). 6 This symptom is most frequently observed in hospitalized patients infected with COVID-19, but liver enzyme abnormalities have been reported in the absence of respiratory symptoms in subjects infected with COVID-19 on rare occasions. 7 F I G U R E 1 Two axial cuts of lung HRCT of the patient on day first of admission Although several pathways have been proposed to be associated with changes in liver enzymes, the exact cause is unknown. The mechanisms postulated include cholangiocyte damage caused by the virus directly binding to angiotensin-converting enzyme 2, hepatic congestion, ischemic hepatitis, cell-mediated apoptosis, venous and arterial thromboses, drugs, and extrahepatic causes of transaminase release such as myositis. 8,9 Hepatitis A virus (HAV) is an RNA virus transmitted via fecal-oral routes and causes fatigue, weakness, malaise, fever, and jaundice. Although ALT and AST levels can exceed 1000 U/dL in hepatitis A, total bilirubin levels rarely exceed 10 mg/dL. Acute hepatitis A infection is diagnosed by the presence of anti-HAV IgM in the serum. There are no specific treatments for Hepatitis A infection, and symptomatic patients should receive supportive care. 10 Herpes simplex virus (HSV) is a DNA virus that causes acute viral hepatitis in a rare number of cases. Clinically, it is indistinguishable from other causes of acute viral hepatitis, and it is frequently associated with a poor prognosis due to delayed diagnosis and treatment. 11 Although there have been reports of COVID-19 coinfection with HSV, no cases of COVID-19 infection with hepatitis A or HSV have been reported to our knowledge.
In this paper, a case was presented of a patient who was simultaneously infected with three viruses.
COVID-19 infection, on the one hand, and concurrent HAV and HSV infections, on the other hand, aggravated liver function in this patient, resulting in severe acute hepatitis. Only two months after the onset of symptoms, all liver chemistries, and coagulation studies returned to normal ranges with supportive treatment.
In conclusion, physicians should consider all possible causes of acute hepatitis when a patient with COVID-19 infection has abnormal liver enzymes, and not all changes should be attributed to COVID-19 infection. Making the correct diagnosis at the appropriate time can significantly affect how patients and the underlying disease are managed.