key: cord-0866944-kg1rl6rb
authors: Butt, Adeel A.; Yan, Peng
title: Rates and Characteristics of SARS‐CoV‐2 Infection in Persons with Hepatitis C Virus Infection
date: 2020-10-02
journal: Liver Int
DOI: 10.1111/liv.14681
sha: 2d842f8c6834f9bb87fc7b12406ab9b708ac555a
doc_id: 866944
cord_uid: kg1rl6rb

BACKGROUND: Rate of SARS‐CoV‐2 infection and impact of liver fibrosis stage upon infection rates in persons with hepatitis C virus (HCV) infection are unknown. METHODS: We retrospectively analyzed the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well‐established database of HCV infected Veterans in care. We excluded those with missing FIB‐4 score and those with HIV or hepatitis B virus coinfection. We determined the number of persons tested, proportion who tested positive for SARS‐CoV‐2, and the infection rate by age and liver fibrosis stage. RESULTS: Among 172,235 persons with HCV, 14,305 (8.3%) were tested for SARS‐CoV‐2 infection and 892 (6.2%) tested positive. Those with SARS‐CoV‐2 infection were older, more likely to be Black (55.2% vs. 37.8%), obese (body mass index >30kg/m(2) 36.2% vs. 29.7%) and have diabetes or stroke (p<0.0001 for all comparisons). Mean FIB‐4 scores and proportion of persons with cirrhosis (based on a FIB‐4 > 3.25) were similar in both groups. Incidence rate/1,000 tested persons was much higher among Blacks (88.4; 95% CI 81.1,96.2) vs. Whites (37.5; 95% CI 33.1,42.4) but similar among those with cirrhosis (FIB‐4>3.25). The rates were also similar among those who were untreated for HCV vs. those treated with or without attaining a sustained virologic response. CONCLUSIONS: Testing rates among persons with HCV are very low. Persons with infection are more likely to be Black, have a higher body mass index and diabetes or stroke. The degree of liver fibrosis does not appear to have an impact on infection rate.

Rate of SARS-CoV-2 infection and impact of liver fibrosis stage upon infection rates in persons with hepatitis C virus (HCV) infection are unknown.

We retrospectively analyzed the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established database of HCV infected Veterans in care. We excluded those with missing FIB-4 score and those with HIV or hepatitis B virus coinfection. We determined the number of persons tested, proportion who tested positive for SARS-CoV-2, and the infection rate by age and liver fibrosis stage.

Among 172,235 persons with HCV, 14,305 (8.3%) were tested for SARS-CoV-2 infection and 892 (6.2%) tested positive. Those with SARS-CoV-2 infection were older, more likely to be Black (55.2% vs. 37.8%), obese (body mass index >30kg/m 2 36.2% vs. 29.7%) and have diabetes or stroke (p<0.0001 for all comparisons). Mean FIB-4 scores and proportion of persons with cirrhosis (based on a FIB-4 > 3.25) were similar in both groups. Incidence rate/1,000 tested persons was much higher among Blacks (88.4; 95% CI 81.1,96.2) vs. Whites (37.5; 95% CI 33.1,42.4) but similar among those with cirrhosis (FIB-4>3.25). The rates were also similar among those who were untreated for HCV vs.

those treated with or without attaining a sustained virologic response.

Testing rates among persons with HCV are very low. Persons with infection are more likely to be Black, have a higher body mass index and diabetes or stroke. The degree of liver fibrosis does not appear to have an impact on infection rate.

This article is protected by copyright. All rights reserved As of August 9, 2020, >20 million persons have been infected and over 730,000 have died of SARS-CoV-2 infection worldwide. While infection rates appear to have diminished significantly in some countries, the pandemic rages on in others, particularly in the Americas. While primarily a respiratory illness, SARS-CoV-2 may affect multiple organ systems. Effects on cardiovascular, 1 renal, 2 gastrointestinal, 3 hepatic, 3,4 endocrine 5 and neurologic systems have been reported. Gastrointestinal symptoms may be present in up to 15% of patients and abnormal liver enzymes in up to 36% of the hospitalized patients. 6, 7 The incidence of SARS-CoV-2 infection among persons with hepatitis C virus (HCV) infection, and its association with degree of liver fibrosis is unknown. Whether persons with HCV experience more severe disease or higher mortality is also unknown. We undertook this study to determine infection rate and clinical characteristics of SARS-CoV-2 infection among persons with HCV infection.

We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) for the current study. Creation of ERCHIVES has been described in numerous previous publications. [8] [9] [10] [11] [12] [13] Briefly, all For the current study, we identified all Veterans in the ERCHIVES database with a positive HCV antibody as well as a positive HCV RNA. We excluded those with missing lab values to calculate the FIB-4 score as the marker for liver fibrosis stage. We also excluded those with HIV or hepatitis B virus coinfection. Comorbidities were defined using established and published definitions. [8] [9] [10] [11] [12] [13] The diagnosis of SARS-CoV-2 infection was confirmed from the VA CDW, where a standard nasopharyngeal swab is tested using RT-PCR to confirm the diagnosis. Liver fibrosis stage was calculated using the FIB-4 score using an average of two values closest to but before baseline.

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We compared the baseline characteristics of all Veterans with HCV in the ERCHIVES cohort who were diagnosed with SARS-CoV-2 with those who tested negative for SARS-CoV-2. We calculated incidence rates per 1,000 persons with 95% confidence intervals by age group, sex, race, liver fibrosis stage and HCV treatment status.

We used SAS® (version 9.4, SAS Institute Inc., Cary, NC, USA) for analyses.

The study was approved by the Institutional Review Board at VA Pittsburgh Healthcare System, Pittsburgh, PA. were similar among those who were untreated for HCV compared with those treated and attained sustained virologic response and those treated and did not attain a sustained virologic response.

We compared the incidence rate of SARS-CoV-2 infection in our HCV positive group with persons without HCV infection. The latter group consisted of all persons in ERCHIVES with a negative HCV antibody test and a negative HCV RNA (if done). Similar to the group with HCV, we excluded those with HIV and HBV coinfection and retained those with lab data to calculated FIB-4 score at baseline.

Among 347,117 persons without HCV infection, the overall SARS-CoV-2 incidence rate per 1,000 persons was 3.7 (95% CI 3.5,3.9; p-value = 0.8 compared with HCV+ group). All-cause mortality rate during the follow-up period was 0.3/1,000 persons for both groups (p-value=0.6).

To our knowledge, this is the first study describing the testing rate and the incidence of SARS-CoV-2 infection in a large national population of persons with HCV infection. We also describe factors associated with infection.

We found that the persons with SARS-CoV-2 infection were more likely to be Black, have a higher body mass index and have diabetes or stroke. Higher rates of infection and poorer clinical outcomes have been described in racial/ethnic minorities and those with comorbidities. More recently, obesity has emerged as an independent risk factor for more severe disease. These associations have not been previously reported in persons with HCV infection. While our current study did not determine the impact of these factors upon mortality or severity of illness, the higher rate of infection coupled with existing literature of their impact upon outcomes should prompt an aggressive testing and monitoring strategy in these persons.

Several small studies (50-363 patients) have assessed the impact of liver disease and/or cirrhosis upon severity of SARS-CoV-2 infection and overall mortality. [14] [15] [16] [17] [18] Presence of advanced fibrosis as

This article is protected by copyright. All rights reserved measured by the FIB-4 score, clinical liver disease or cirrhosis are all associated with a higher risk of more severe disease or higher mortality. The cause of liver disease, and more specifically presence of HCV infection were not uniformly reported. Furthermore, there are no estimates of testing for SARS-CoV-2 and infection rates among persons with HCV and the impact of liver fibrosis or cirrhosis upon the testing or infection rates. We found that the degree of liver fibrosis as measured by the noninvasive FIB-4 score was similar and a similar proportion had advanced fibrosis or cirrhosis.

Incidence rate was also similar regardless of the liver fibrosis stage at baseline. Additionally, treatment of HCV and attainment of sustained virologic response did not seem to affect the rate of infection.

Strengths of our study include a large national sample with relatively easy and free access to testing.

However, lack of widespread testing limits the generalizability of our findings. Some Veterans may have been tested outside the VA healthcare system which may have skewed the results. Effect of various factors upon severity of disease and mortality require further study.

This study provides compelling data regarding SARS-CoV-2 infection in persons with HCV infection with several notable points for clinicians and policy makers. The overall testing rate in persons with HCV is extremely low. When tested, infection appears to disproportionately affect minorities, obese persons and those with certain comorbidities. However, degree of liver fibrosis does not appear to increase the risk of infection. Similarly, infection rates are comparable among those who never received HCV treatment and those who received treated with or without attainment of viral eradication.

This article is protected by copyright. All rights reserved 

This article is protected by copyright. All rights reserved 

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