Epidemiological and Clinical Characteristics of 70 Cases of Coronavirus Disease and Concomitant Hepatitis B Virus Infection

A Multicentre Descriptive Study

Jian Wu; Jiong Yu; Xiaowei Shi; Wei Li; Shu Song; Liangping Zhao; Xinguo Zhao; Jun Liu; Dawei Wang; Chengyuan Liu; Biao Huang; Yiling Meng; Bin Jiang; Yijun Deng; Hongcui Cao; Lanjuan Li

Disclosures

J Viral Hepat. 2020;28(1):80-88. 

In This Article

Discussion

In this study, we retrospectively investigated the epidemiologic and clinical characteristics as well as treatment, and prognosis of 70 cases of COVID-19 and concomitant HBV infection from seven hospitals in Jiangsu, Hubai, Anhui, and Zhejiang Provinces, and analysed the risk factors for delayed recovery from COVID-19. This may be the first report on the interaction between preexisting chronic liver disease and COVID-19.

COVID-19 is primarily transmitted by respiratory droplets and contact transmission.[23] Compared to the WHI group, a higher proportion of patients in the CHI group belonged to Generation IV and a lower proportion belonged to Generation I, which may indicate that patients with COVID-19 and concomitant HBV infection are more susceptible to COVID-19 than the general population is. Our study also showed a higher proportion of severe/critically ill patients in the CHI group than in the WHI group. Several studies have shown that underlying diseases are risk factors for COVID-19 progression.[24,25] HBV can cause hepatic inflammatory damage leading to compensatory proliferation of hepatocytes derived from bile duct epithelial cells, eventually resulting in new hepatocytes carrying ACE2 expressed in the sinusoidal endothelial cells.[26] SARS-CoV-2 mediates infection[27] mainly by entering the cells through human ACE2.

In laboratory examination findings, the frequency of abnormal levels of WBC, lymphocyte count and CRP was consistent with previous studies.[10,28] The proportions of patients in the CHI group showing abnormal ALT and/or AST levels were significantly higher than that in the WHI group. Meanwhile, APTT levels in the CHI group was significantly higher than in the WHI group. Severe cases of COVID-19 with liver dysfunction were accompanied with a higher degree of activation of the coagulation and haemolytic fibre pathway. Additionally, in posthepatic cirrhosis and chronic severe hepatitis, APTT is significantly prolonged.[29] In this study, majority of patients in the CHI group received effective anti-HBV treatment prior to SARS-CoV-2 infection, so some parameters of liver disease such as albumin and platelets, in these patients were not significantly abnormal compared with the WHI group.

Currently, there are no specific therapeutic drugs for COVID-19.[30] According to guidelines from the WHO[21] and the National Health Commission of the People's Republic of China, patients with moderate disease should receive timely treatment with antiviral therapy, such as coriolus, Arbidol, chloroquine phosphate, and reconstituted human interferon alfa-2b injection. For severe/critically ill patients, respiratory support, appropriate dose of hormone therapy, and/or Traditional Chinese Medicine can be scheduled as an auxiliary therapeutic modality. In our study, we compared the utilization rates of antiviral drugs between the two groups. Since chloroquine phosphate can cause significant liver damage, the utilization rate of chloroquine in the CHI group was significantly lower. Simultaneously, we found that the utilization rate of immunoglobulin in the CHI group was higher, as immunoglobulin therapy has antiviral effects, improves the phagocytic activity of immune cells, and can kill and dissolve pathogenic microorganisms under the synergistic action of the complement system, which is an important defence mechanism in the body's immunity to infections.[31,32]

In this study, we also analysed the outcomes of patients with COVID-19 and concomitant HBV infection. The mortality rate was 2.26%, which was lower than the average rate in China. The reason was that the mortality rates in the provinces of Anhui, Jiangsu, and Zhejiang were significantly lower than in other regions due to timely treatment and effective interventions. In our study, the results showed that the time of average hospital stay and nucleic acid test yielding negative results in patients in the CHI group were both consistent with those in the WHI group, indicating no differences in outcomes between the two groups. This result could account from the following reasons: first, most patients in the CHI group in the study had their liver disease under control by anti-HBV therapy before admission, and after admission, they were also provided targeted available treatment, such as drugs for liver protection and hepatic enzyme reduction; second, the number of patients (n = 70) in this study was relatively low.

Finally, we analysed the risk factors affecting the recovery of patients with COVID-19 and concomitant HBV infection, and the results showed that age and CRP level were independent risk factors affecting recovery from COVID-19. Due to the degradation of physiological function and immune response in the elderly, drug toxicity tolerance of the liver is reduced.[33] Simultaneously, the risk of drug-induced liver damage is significantly increased due to several reasons, such as the multiple comorbidities and the variety and quantity of drugs taken, etc[34] A high level of CRP promotes the release of pro-inflammatory factors such as procalcitonin (PCT) and interleukin-6, forming a cascade reaction, and the expressions of various inflammatory mediators interact with and promote each other, therefore aggravating the inflammatory response in patients.[35] The level of CRP is related to the degree of inflammation and infection. Therefore, considering the patient's age and monitoring the CRP level is helpful for physicians to judge their prognosis. It should be noted that the three important parameters of liver function, ALT, ALB, and HBsAg were not independent risk factors affecting recovery, suggesting that patients with COVID-19 and concomitant HBV infection are not at an increased risk of delayed recovery.

This study had several limitations. First, all the enrolled cases were from seven hospitals in four provinces, making the study subject to selection bias with considerable heterogeneity between units. Second, the number of cases of COVID-19 and concomitant HBV infection was relatively small. Larger samples are needed to confirm the results of this study. Third, several important indicators of liver disease, such as ultrasound, liver fibrosis, etc, were not clinically evaluated, thus impacting the in-depth evaluation of this study.

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