Acute Hepatitis as a Rare Presentation of COVID-19

By Abat Khan¹, Ihtisham Qayum², Abdul Wali Khan³, Muhammad Hanif¹, Awais Naeem²

Affiliations

1. Department of Cardiology, Khyber Teaching Hospital, Peshawar, Pakistan
2. Department of Internal Medicine, Khyber Teaching Hospital, Peshawar, Pakistan
3. Department of Internal Medicine, Hayatabad Medical Complex, Peshawar, Pakistan

doi: 10.29271/jcpsp.2021.07.125

ABSTRACT
Coronavirus disease 2019 (COVID-19) initially emerged in Wuhan, China, in December 2019, and now it has been declared a pandemic by the World Health Organization. COVID-19 commonly presents with respiratory manifestations like fever, cough, body aches, and shortness of breath. Neurological, myocardial, renal and gastrointestinal complications secondary to SARS-CoV-2 infection have been reported in the literature. Gastrointestinal symptoms reported with COVID-19 are mostly nausea, vomiting, and diarrhea. COVID-19 can rarely present with acute hepatitis. Here, we report a case of a 45-year male who presented with signs and symptoms of acute hepatitis secondary to SARS-CoV-2 infection.

Key Words: SARS-CoV-2, COVID-19, Acute hepatitis.

INTRODUCTION

Coronavirus disease 2019 (COVID-19) initially began as clusters of atypical pneumonia in Wuhan, China, in December 2019, and now it has caused approximately one million deaths around the globe. SARS-CoV-2 infection is mostly asymptomatic and commonly presents with respiratory symptoms like fever, shortness of breath, and cough.¹ In the literature, COVID-19 has been reported with various renal, myocardial, neurological, and gastrointestinal complications.^2,3  Similarly, hepatobiliary complications, i.e. abnormal liver function tests and rarely acute hepatitis, have been reported with SARS-CoV-2 infection.⁴ Wander et al. reported the first case of acute non-icteric hepatitis caused by SARS-CoV-2, who presented to the emergency department with dark urine and was later diagnosed as a case of acute hepatitis secondary to SARS-CoV-2.⁵ Here, we report a case of a 45-year male patient who initially presented with signs and symptoms of acute hepatitis and was later on diagnosed with acute hepatitis secondary to SARS-CoV-2 infection.

CASE REPORT

A 45-year male with an insignificant past medical history presented to the Emergency Department with five days’ history of nausea, vomiting, and fever.

On examination, his blood pressure was 115/75 mmHg, pulse 110/min, oxygen saturation 96%, and temperature was 101˚F. Abdominal examination was unremarkable except for tender right hypochondrium.  Baseline investigations showed a high level of alanine aminotransaminase (ALT) 1750 U/L, aspartate aminotransaminase (AST) 1801 U/L, total bilirubin of 2 mg/dl, and an alkaline phosphatase of 204 U/L. He was admitted as a case of acute hepatitis in the isolation unit and started on intravenous dextrose saline 1000 ml twice a day, injectable dimenhydrinate as needed, and omeprazole 40 mg once a day. As per the hospital's protocol, inflammatory markers and a nasopharyngeal swab test for COVID-19 on quantitative reverse-transcriptase-polymerase-chain reaction (qRT-PCR) assay were sent. The inflammatory markers were raised (Table I), and he developed a dry cough on the second day of admission.

Chest X-ray showed mild bilateral infiltrates. He was started on injectable azithromycin 10 mg/kg/day, ceftriaxone 50 mg/kg/day, and enoxaparin 40 mg subcutaneous once a day. Serological tests for hepatitis A, B, C, and E viruses, Epstein-Barr virus, cytomegalovirus virus, blood cultures, and autoimmune markers were negative (Table II).

The qRT-PCR result was positive for SARS-CoV-2 infection. The patient had no history of alcohol intake and hepatotoxic drug use. He was diagnosed with acute hepatitis secondary to SARS-CoV-2, because no other causative factor was found despite thorough work-up. On fifth day of admission, his condition improved, and he was discharged and was advised to follow-up as an outpatient.

DISCUSSION

SARS-CoV-2 causing COVID-19 mostly presents as fever, cough, shortness of breath, fatigue, and headache. Acute hepatitis associated with SARS-CoV-2 has been rarely reported. For instance, the first biopsy-proven acute hepatitis secondary to SARS-CoV-2 in a female infant who was a liver allograft recipient and whose donor subsequently tested positive for COVID-19 was reported by Lagana et al.⁶

Table I: Laboratory findings.

Test	Result
Hemoglobin	11.4 g/dl
Total lymphocyte count	13.8×109/l
Red blood cells	4.3 ×1012/l
Platelets	390×109/l
Prothrombin time	13  seconds (12 seconds control)
Activated partial thromboplastin time	33 seconds (28 seconds control)
D-dimers	874 ng/FEUml (reference value: upto 500 ng/FEUml)
C-Reactive protein	17.2 mg/dl
Lactate dehydrogenase (LDH)	725 U/l
Serum Ferritin	1178.6 µg/l
Alanine aminotransaminase (ALT)	1750 U/l
Aspartate aminotransaminase (AST)	1801 U/l
Alkaline phosphatase	204 U/l
Total bilirubin	2 mg/dl
Blood urea	51 mg/dL
Creatinine	0.6 mg/dl
Sodium	137.2 mEq/l
Potassium	3.92 mEq/l

Table II: Additional laboratory findings.

Investigations	Results
Anti-hepatitis A antibody (IgM/IgG)	Negative/Negative
HBs antigen	Negative
Anti-HBs antibody	Negative
Anti-HBc antibody	Negative
Anti-HCV antibody	Negative
Anti-Hepatitis E antibody (IgM/IgG)	Negative/Negative
Anti-CMV antibody ( IgM/IgG)	Negative/ Negative
Anti-EBV antibody (IgM/IgG)	Negative/ Negative
Blood Culture	Negative for any pathogens
ANA Screening	Negative

Chen et al. conducted a study to evaluate clinical manifestations in 99 COVID-19 patients and found that 35 % of patients had a mild elevation of AST (mean 34 U/L) and 28% a mild elevation of ALT (mean 39 U/L), but only one (0.9%) out of 99 patients had a high level of ALT and AST (ALT, 7590 U/L, AST, 1445 U/L).⁷ Several mechanisms have been proposed to explain how SARS-CoV-2 causes liver injury. The possible mechanisms include: Immune-mediated injuries: Inflammatory biomarkers could be the cause of liver injuries in COVID-19 patients as they are significantly elevated in COVID-19 patients.⁸ Hypoxic and Anoxic injuries: Respiratory failure is the hallmark of COVID-19, and hypoxia and anoxia could be the possible cause of hepatic injuries.⁸ Direct cytotoxicity: Angiotensin-converting enzyme 2 (ACE2) receptors the potential targets of SARS-CoV-2 viral entry. ACE2 receptors are abundant in the liver and could be the cause of liver injuries.⁹Mild hepatic damage is common in SARS-CoV-2 due to the above possible mechanisms, but severe acute hepatitis is a rare occurrence. In our case, the patient presented with signs and symptoms of acute hepatitis and was later diagnosed as COVID-19.

Acute hepatitis is an atypical and rare presentation of COVID-19, which occurred before developing typical respiratory symptoms of cough, shortness of breath in this case. During this pandemic, physicians should keep in mind such rare manifestations and presentations of SARS-CoV-2 infections to decrease the spread and mortality of COVID-19.

PATIENT'S CONSENT:
Written informed consent was taken from the patient.

CONFLICT OF INTEREST:
The authors declared no conflict of interest.

AUTHORS' CONTRIBUTION:
AK: Collected the data.
AK, IQ, AWK, MH and AN: Wrote the initial manuscript.
MH and AWK: Critically revised the manuscript.
All authors have read the final manuscript.

REFERENCES

1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalised patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323(11):1061-9. doi:10.1001/jama.2020.1585.
2. Ahmed MU, Hanif M, Ali MJ, Haider MA, Kherani D, Memon GM, et al. Neurological manifestations of COVID-19 (SARS-CoV-2): A review. Front Neurol 2020; 11:518. doi:10.3389/ fneur.2020.00518.
3. Tian Y, Rong L, Nian W, He Y. Review article: Gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther 2020; 51(9):843-51. doi:10.1111/apt.15731.
4. Patel KP, Patel PA, Vunnam RR, Hewlett AT, Jain R,  Jing R, et al. Gastrointestinal, hepatobiliary, and pancreatic manifestations of COVID-19. J Clin Virol 2020; 128:104386. doi:10.1016/j.jcv.2020.104386.
5. Wander P, Epstein M, Bernstein D. COVID-19 Presenting as Acute Hepatitis. Am J Gastroenterol 2020; 115(6):941-2. doi:10.14309/ajg.0000000000000660.
6. Lagana SM, De Michele S, Lee MJ, Emond JC, Griesemer AD, Tulin-Silver SA, et al. COVID-19-associated hepatitis complicating recent living donor liver transplantation. Arch Pathol Lab Med 2020; 10.5858/arpa.2020-0186-SA. doi:10.5858/arpa.2020-0186-SA.
7. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020; 395(10223):507-13. doi:10.1016/S0140-6736(20)30211-7.
8. Sun J, Aghemo A, Forner A, Valenti L. COVID-19 and liver disease. Liver Int 2020; 40(6):1278-81. doi:10.1111/ liv.14470.
9. Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv 2020. doi.org/10.1101/ 2020.02.03.93176.