COVID-19 Severity and Mortality Among Chronic Liver Disease Patients

A Systematic Review and Meta-Analysis

Ramya Nagarajan, MD; Yuvaraj Krishnamoorthy, MD; Sathish Rajaa, MD; Vishnu Shankar Hariharan, MD


Prev Chronic Dis. 2022;19(8):e53 

In This Article

Abstract and Introduction


Introduction: Pre-existing comorbid conditions in COVID-19 patients are risk factors for developing severe disease and death. We aimed to determine the association of chronic liver disease (CLD), a comorbid condition, with severity of disease and death among COVID-19 patients.

Methods: We searched for studies reporting COVID-19 outcomes among CLD and non-CLD patients in databases including Medline, EMBASE, ScienceDirect, Google Scholar, and Cochrane Library from inception of the pandemic until February 2022. Risk of bias assessment was conducted by using the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses. We conducted a meta-analysis with a random-effects model and reported pooled odds ratios (ORs) with 95% CIs.

Results: We included 40 studies with 908,032 participants. Most studies were conducted in China and the US. COVID-19 patients with CLD had significantly higher odds of having a severe form of COVID-19 (pooled OR = 2.44; 95% CI, 1.89–3.16) and death (pooled OR = 2.35; 95% CI, 1.85–3.00) when compared with COVID-19 patients without CLD.

Conclusion: The presence of CLD is significantly related to adverse clinical outcomes among COVID-19 patients in terms of severity and mortality. Clinicians should develop a comprehensive intervention plan to manage these high-risk patients and reduce COVID-19–related deaths.


A coronavirus is a group of viruses that causes mild to severe respiratory tract infections in humans and animals.[1] In recent times, we have witnessed outbreaks of severe acute respiratory syndrome (SARS) virus (2004), Middle East Respiratory Syndrome coronavirus (MERS-CoV) (2012), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (2019) that belong to this group of viruses.[2] The SARS-CoV-2 outbreak is the most recent and was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020.[3] As of May 16, 2021, 162 million cases and 3 million deaths were reported globally due to COVID-19.[4] The clinical features range from asymptomatic infection to severe pneumonia and death. However, patients who have comorbidities are more likely to have a severe form of the condition or to die.[5]

Chronic liver disease (CLD) is marked by the gradual destruction of liver parenchyma over time. Various factors cause it; the most common are alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), chronic viral hepatitis, and genetic and autoimmune causes.[6] Understanding the conditions that lead to severe disease and death among COVID-19–infected people is critical with the evolving pandemic.[7] COVID-19 infection highlights the pre-existing weaknesses of the individual organ systems,[8] making it logical to postulate that people with CLD may be susceptible to more severe respiratory infections or be at increased risk of death. In addition, it has been proposed that metabolic-associated fatty liver disease (MAFLD) or NAFLD is associated with significant or advanced fibrosis that might exacerbate the "cytokine storm" induced by the COVID-19 infection.[9] The mechanism behind this is probably through the release of various proinflammatory hepatokines, which might contribute mechanistically to developing a severe form of COVID-19 infection.[9] Several studies have found that hospitalized COVID-19 patients with CLD had an acute rise in liver enzymes, which results in a severe condition requiring mechanical ventilation and even leading to death.[10–12] Existing evidence on COVID-19 outcomes among CLD patients has reported mixed results, making it difficult to determine a prognosis for these patients.[10–13] Hence, we conducted a systematic review and meta-analysis to find the association between CLD and the severity of and mortality caused by COVID-19.