Histological features of liver biopsy in patients with COVID-19: a single institution experience with long term follow-up outcome

COVID-19 is caused by SARS-CoV2, which primarily produces respiratory disease. Although liver enzyme abnormalities are common in patients with COVID-19, little is known about histological changes in the liver. Most of the available information is based on autopsy studies, with limited liver biopsy studies in living patients. Liver biopsies performed between March 2021 and September 2021 in patients with a history of COVID-19 were retrieved, and 17 biopsies were reviewed. Additionally, immunohistochemical staining for the SARS-CoV2 nucleocapsid protein was performed in all cases. The clinical follow-up period was 36 months. After reviewing the clinical data, the biopsies were grouped into three cohorts: (1) those with no underlying liver disease, (2) those with preexisting liver disease, and (3) those with liver post-transplant allografts. In patients without underlying liver disease, there were small clusters of debris-laden macrophages in the portal areas and lobules, as highlighted by periodic acid-Schiff and diastase staining. Increased mitosis and binucleated hepatocytes were common, and rare micro-abscesses were also observed. These findings indicated mild non-specific hepatitis, and no severe inflammatory infiltrates were observed in portal areas or lobules. These features are highly suggestive of hepatitis resolution. Patients with previous liver disease showed microscopic features compatible with underlying liver disease, without any additional features that could be attributed to COVID-19. Posttransplant allograft biopsies showed no special features that could be described as occurring solely due to COVID-19. All patients tested negative on SARS-CoV2 nucleoprotein immunostains. Liver biopsies performed after COVID-19 demonstrated a mildly resolved hepatitis-like pattern. 36 months after biopsy, all patients in Group 1 and all surviving patients in Group 2 and 3 presented normal liver enzyme levels. It is therefore, from this small case series, that the liver may not be the target of significant inflammatory damage in COVID-19 and that liver injuries are resolved over time. • Liver biopsies of patients with no prior liver disease following COVID-19 infection showed mild non-specific hepatitis, indicating recent liver injury. • Liver biopsy with underlying liver disease presents a different type of challenge due to its overlapping histological features with COVID-related hepatitis, and no specific features could be described as occurring solely due to COVID-19. • All patients were negative for SARS-CoV2 nucleoprotein, which raises the question of whether liver damage was not the direct result of viral infection but a reactive response to cytokines produced during the infection.