Introduction
In December 2019, a novel coronavirus was considered the cause of a group of pneumonia cases in Wuhan, a city in Hubei Province, China. It spread rapidly and resulted in an epidemic across China, followed by a worldwide pandemic with almost 2 million confirmed cases (1). In February 2020, the World Health Organization officially named the disease as “Coronavirus disease-2019 (COVID-19)”, which stands for coronavirus disease 2019. The virus that caused COVID-19 was named as Severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2). Although severe COVID-19 disease can occur in healthy individuals of all ages, it has been observed to affect predominantly adults with advanced age or underlying diseases (2). By reporting this case, we emphasized that COVID-19 should also be included in the differential diagnosis of patients presenting with acute hepatitis during the pandemic.
Case Report
A 55-year-old male patient presented to our outpatient clinic with complaints of dark urine and fatigue for two days. He did not exhibit dry cough, dyspnea, elevated fever, sore throat, runny nose, headache, myalgia, disrupted sense of smell and taste, and diarrhea, which are the symptoms of COVID-19. Moreover, COVID-19 was not considered in the foreground as the patient did not report a history of traveling out of the city in the last 14 days and contact with anyone diagnosed with COVID-19. The patient’s history revealed primary hypertension, diabetes mellitus type-2 and osteoporosis, and the medications used for these conditions as follows: nifedipine, calcium citrate, vitamin D, and metformin. Part of this, it was learned that he did not use any medicine or herbal product within the last week. His physical examination revealed no pathological findings, and his vital signs were as follows: pulse 70 bus, blood pressure 110/75 mmHg and body temperature 36.7 °C. Laboratory results were as follows: hemoglobin 13.5 g/dL (13.5-17.5 g/dL), white blood cell 8100 cells/mcL (3.500-10.500 cells/mcL), platelet count 172,000 mcL (150.000-450.000/mcL), serum creatinine 1.1 mg/dL (0.6-1.2 mg/dL), blood urea nitrogen 19 mg/dL (6-20 m/dL), sodium 135 mmol/L (136-146 mmol/L), potassium 4.3 mmol/L (3.5-5.1 mmol/L), calcium 8.9 mg/dL (8.8-10.6 mg/dL), phosphorus 2.8 mg/dL (2.5-4.5 mg/dL), alanine aminotransferase (ALT) 821 IU/L (0-50 IU/L), aspartate aminotransferase (AST) 1042 IU/L (0-50 IU/L), alkaline phosphatase (ALP) 412 IU/L (40-150 IU/L), gamma-glutamyl transferase (GGT) 268 IU/L (9-64 IU/L), lactate dehydrogenase 231 IU/L (0-248 IU/L), uric acid 6.0 mg/dL (3.5-7.2 mg/dL), total bilirubin 0.52 mg/dL (0.3-1.2 mg/dL), unconjugated bilirubin 0.49 mg/dL (0.0-0.8 mg/dL), conjugated bilirubin 0.03 mg/dL (0.0-0.2 mg/dL), international normalized ratio (INR) 1.02 (0.8-1.2), albumin 3.0 g/dL (3.5-5.2 g/dL), C-reactive protein (CRP) 7 mg/dL (5-10 mg/dL), glucose 88 mg/dL and hematuria was detected in the complete urinalysis. Hepatitis A, B, C, E, human immunodeficiency virus, Cytomegalovirus, Epstein-Barr virus, Brucella melitensis, and Toxoplasma gondii serology and blood culture were negative. Autoimmune markers studied to rule out autoimmune diseases of the liver were negative. Abdominal ultrasonography (USG) and Doppler USG showed no pathological findings other than grade-1 hepatosteatosis in the liver. On the third day of hospitalization, the patient developed dyspnea and low saturation (SaO2 93%) with 38.7 °C fever. The posteroanterior chest X-ray revealed bilateral opacities in the middle zones, whereas the subsequent lung computed tomography revealed a segmental consolidation scattered across the subpleural areas in the middle zones, which was evaluated to be consistent with COVID-19. The nasopharyngeal swab sample tested positive for SARS-CoV-2 because of reverse transcriptase-polymerase chain reaction assay. The patient was administered 200-mg hydroxychloroquine for 5 days in accordance with the treatment protocol applied in Turkey. The post-treatment laboratory results of the patient with good general condition and stable vital signs were as follows: ALT: 117 IU/L, AST: 221 IU/L, ALP: 171 IU/L, GGT: 97 IU/L, total bilirubin: 0.41 mg/dL, INR: 0.9, albumin: 3.7 g/dL, CRP: 3 mg/dL. The patient was discharged upon improved laboratory values and no pathological findings on vital signs and physical examination.
Discussion
The person-to-person transmission was confirmed with the rapid increase in the number of cases following the first reports of COVID-19 along with the emergence of the disease among healthcare workers (3). Although believed to be transmitted by droplets, recent cases have revealed evidence of transmission without any contact with infected individuals. It is considered that asymptomatic individuals may carry the virus in the airways and cause transmission, but transmission mainly occurs via contact with infected individuals. The clinical outcomes of COVID-19 can be mild and severe, with varying degrees or even clinical outcomes lead to death (4). To date, it remains unclear why some patients have developed severe symptoms. Recently, an article reported that COVID-19 affected liver metabolism, but acute hepatitis occurs rarely after COVID-19. Various degrees of liver damage have been observed in COVID-19 patients (5). Recent studies have shown that COVID-19 patients exhibit elevated AST or ALT in case of severe liver damage, whereas the elevation of bilirubin is mild (6). Although the elevation of liver enzymes is mild to moderate in most cases, a case presenting with acute hepatitis before the development of respiratory symptoms was recently published (7). Furthermore, Weber et al. (8) recently presented a case of severe hepatic impairment in a COVID-19 patient with a high model for end-stage liver disease score who had no previous liver disease. However, there is currently insufficient data on cirrhosis and other complications in patients with COVID-19; therefore, there is a need for more research. Although the mechanism of liver damage associated with SARS-CoV-2 remains unclear, the cause of elevated liver enzymes may be the direct effect of the virus on the liver with the angiotensin-converting enzyme 2 (ACE2) receptors (9). Previous studies have shown that ACE2 receptors are expressed in both bile duct and liver cells, but the concentration of ACE2 receptors in hepatocytes is much lower, indicating that liver damage is due to the damage to cholangiocytes (10). However, histopathological liver findings of COVID-19 patients did not exhibit any significant hepatocyte and cholangiocyte damage as cholestatic liver enzymes do not usually increase in COVID-19 patients with liver damage (11). Liver damage in COVID-19 patients may be caused by a hyperactive immune response and cytokine storm or systemic inflammation due to drug hepatotoxicity. Therefore, close patient follow-up and monitoring of liver function are required (12).
Conclusion
In conclusion, our patient’s fever and dyspnea improved within a few days without any specific treatment, and the liver function parameters were found to decreased significantly on the fifth day following the diagnosis of COVID-19. Acute hepatitis appears quite rarely, considering that a new symptom and clinical condition are associated with COVID-19 every day. Elevated liver function parameters in individuals without significant COVID-19 symptoms should be regarded as an indicator of COVID-19.
Ethics
Informed Consent: Consent form was filled out by all participants.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: M.N.K., Concept: M.N.K., Design: S.F.S., Data Collection or Processing: M.N.K., Analysis or Interpretation: M.N.K., Literature Search: S.F.S., Writing: M.N.K.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.