Poor Response to Inactivated SARS-CoV-2 Vaccine in Patients With Chronic Liver Disease.

Dear Editor:

We read with great interest the article by Jingwen Ai et al recently published in Clinical Gastroenterology and Hepatology, showing that patients with chronic liver diseases (CLD) had lower immunologic response to SARS-CoV-2 vaccines than healthy populations. This multicenter study is the first to evaluate the safety and immunogenicity of SARS-CoV-2 vaccine in the real-world population with CLD, and its results were important and timely for guiding clinical practice during the current COVID-19 pandemic. More importantly, this study supported that patients with CLD, especially cirrhosis, are those we should pay much more attention to following vaccination. However, some aspects need further discussion.

First, the range of the time interval from the second dose to serum collection was not reported. A recent study proved that the SARS-CoV-2 IgG seropositivity declined over time since vaccination for Sinovac's inactivated CoronaVac vaccine recipients. The IgG positivity reached a peak of 77.4% during Week 3 and decreased to 47.3% during Week 16 after the second dose. Therefore, we suggested that the authors should analyze the correlation between blood collection time points with antibody titer. The results will be very important to understand the decline pattern of antibody titers after SARS-CoV-2 vaccine, and valuable for determining the time of the third vaccination dose for patients with CLD.

Second, patients with cirrhosis are considered immunocompromised and usually have poor response to vaccination, which has been demonstrated in several studies regarding vaccines of influenza, hepatitis A, and hepatitis B.3, 4, 5 The underlying mechanism is that cirrhosis impairs the T-cell activation and synthesis of innate immunity proteins and pattern recognition receptor. , However, the current study showed that the neutralizing antibody concentration was 20.5 (10.4–36.4) AU/mL in the decompensated cirrhotic group, which was higher than those in the healthy control subject group 18.8 (13.4–27.7) AU/mL. It will be interesting and informative to know the reasons for these unexpected differences.

Third, the authors also included participants with autoimmune diseases, such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, in the study. The immune response after vaccination among patients with CLD with autoimmune diseases may be different from those without autoimmune diseases. Previous study had demonstrated that the level of neutralizing antibodies in patients with systemic autoimmune rheumatic disorders was lower than that in the healthy control subjects and not related to ongoing treatments. Therefore, we suggested that the patients with autoimmune disease should be analyzed separately.

Finally, a total of 3 participants reported grade 3 alanine aminotransferase elevation and 1 of them was hospitalized. We noticed that these 3 patients had elevated alanine aminotransferase level before vaccination. So, whether patients with abnormal alanine aminotransferase should postpone the COVID-19 vaccination needs further investigation.