Post-COVID-19 cholangiopathy: Systematic review

ARTICLE HIGHLIGHTS

Research background

The coronavirus disease 2019 (COVID-19) pandemic, declared by the World Health Organization in March 2020, has had devastating global impacts, resulting in millions of deaths and significant economic and humanitarian losses. Despite vaccination efforts, new variants of the virus continue to pose a threat, hindering control measures. While respiratory symptoms are common in COVID-19, extrapulmonary manifestations and derangement of liver enzymes have been observed. One emerging complication is post-COVID-19 cholangiopathy (PCC), characterized by bile duct inflammation and damage in recovered individuals. PCC presents with symptoms such as abdominal pain, fever, and jaundice, affecting both severe and milder cases. The prevalence and potential drug associations with PCC remain uncertain.

Research motivation

Understanding post-COVID-19 cholangiopathy is crucial due to its novelty and potential impact on recovered patients. Exploring the clinical presentation and management of PCC can provide valuable insights into its diagnosis and treatment. By addressing the knowledge gaps surrounding this condition, future research can develop effective strategies for patient care and improve outcomes in clinical practice. The significance of solving these problems lies in advancing our understanding of this novel disease and facilitating evidence-based approaches to manage post-COVID-19 cholangiopathy.

Research objectives

The primary objectives of this systematic review were to comprehensively analyze and synthesize existing evidence on post-COVID-19 cholangiopathy, focusing on the clinical presentation and management approaches documented in reported cases. By realizing these objectives, we provide a comprehensive overview of the current understanding of post-COVID-19 cholangiopathy, identify knowledge gaps, and contribute to the development of effective diagnostic and therapeutic strategies for this condition. The findings from this study can guide future research endeavors, leading to improved patient care and outcomes in the field of post-COVID-19 cholangiopathy.

Research methods

The research methods employed in this study adhered to the guidelines for preferred reporting items for systematic reviews and meta-analyses protocols. A comprehensive search was conducted in electronic databases (Scopus, Web of Science, and Medline/PubMed) using specified search terms. The search was limited to English, Spanish, and Portuguese language publications without any date restrictions. In addition to database searches, the reference lists of identified studies were manually searched. The inclusion criteria encompassed clinical case reports or case series focusing on post-COVID cholangiopathy, with detailed information on clinical presentation, diagnosis, management, and outcomes. Studies that lacked relevant clinical information or were unrelated to the topic were excluded. Two independent reviewers performed data extraction using a standardized form, and any discrepancies were resolved through discussion or consultation with a third reviewer. The extracted data included variables such as age, sex, clinical presentation, liver and renal function tests, imaging findings, histopathology, liver transplantation status, and outcomes. Data analysis involved descriptive techniques, including frequencies, means, and medians.

Research results

This systematic review identified a total of 540 patients with post-COVID-19 cholangiopathy, predominantly male (12.7%) and over 50-years-old (12.2%). Elevated liver enzymes were observed in nearly all patients during the acute phase (93.8), persisting in the chronic phase. Total bilirubin levels were elevated in 63.5% of cases, while alkaline phosphatase was 488 (90.3%) and gamma-glutamyl transferase levels consistently exceeded 1000 U/L. Imaging findings revealed biliary ductal dilatation with fibrosis on ultrasound in 41.6% of patients and bile duct thickening with contrast enhancement on MRI in 47.7% of patients. Respiratory failure type 2, associated with acute respiratory distress syndrome, was observed in 41.3% of patients, with 1 patient undergoing lung transplantation. Acute renal injury requiring dialysis or renal transplantation was present in 65.7% of cases. Liver biopsy showed sclerosing cholangitis in 74.4% of patients. Sixteen patients (2.96%) underwent orthotopic liver transplantation, with successful outcomes observed in 93.75% of these cases. These findings provide important insights into the clinical characteristics and complications of post-COVID-19 cholangiopathy, highlighting the need for further research to elucidate its pathogenesis and optimal management strategies.

Research conclusions

This study proposes several new theories and methods in the field PCC. First, the study suggests that PCC is a serious systemic illness that affects not only the lungs but also the liver. It provides evidence that PCC is characterized by elevated liver enzymes, biliary ductal dilatation, and histopathological findings of secondary sclerosing cholangitis. The study highlights the importance of considering the differential diagnosis, as other diseases may present with similar symptoms, such as ketamine-induced cholangiopathy and ischemic cholangitis. The study emphasizes the diagnostic procedures for PCC. It recommends the use of cholangiography, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography to visualize the biliary system and identify characteristic features of PCC, such as pruned tree appearance, beaded ducts, and band-like strictures.

Research perspectives

The future research in the field of PCC should focus on understanding its pathophysiology, including the mechanisms of bile duct paucity and unique microvascular features. Improving diagnostic procedures through novel imaging techniques and biomarkers is essential for early and accurate detection. Comparative studies with other cholangiopathies can enhance treatment approaches. Additionally, investigating the management and treatment of PCC, including the efficacy of liver transplantation, is crucial. Identifying predictive factors for transplantation and determining long-term prognosis are valuable areas of research. Overall, future studies should deepen our understanding, develop improved diagnostics, and explore effective treatments to enhance patient outcomes. Collaboration among researchers and international efforts will play a vital role in advancing knowledge and management of this disease.