Patients hospitalized with COVID-19 who carry a pre-existing diagnosis of chronic liver disease face a substantially higher risk of dying in hospital than comparable patients whose livers are healthy, according to a retrospective cohort study conducted at Ayatollah Rouhani Hospital in Babol, a city in northern Iran. The research, published in the journal Gut Pathogens, followed 114 hospitalized patients with confirmed SARS-CoV-2 infection over a three-year window spanning March 2020 to March 2023, a period that covered multiple waves of the pandemic in the region. The findings add to a growing body of evidence that the liver, far from being a bystander in COVID-19, is deeply entangled in the systemic storm the virus can unleash.
The study team, led by Reza Zabihi of the Student Research Committee at Babol University of Medical Sciences together with colleagues from the university’s departments of internal medicine, social determinants of health, and infectious diseases research, designed the investigation as a matched-style comparison rather than a simple survey of liver patients. They enrolled 37 hospitalized COVID-19 patients with documented pre-existing chronic liver disease and selected 77 comparison patients who were hospitalized with confirmed COVID-19 but had neither chronic liver disease nor other documented chronic comorbidities. This deliberate selection of a relatively clean comparison group is analytically important: by stripping away diabetes, cardiovascular disease, and other common confounders, the researchers sought to isolate the contribution of liver pathology itself to COVID-19 outcomes, rather than the contribution of multimorbidity in general.
The demographic profiles of the two groups were closely aligned. The mean age in the chronic liver disease group was 57.03 years with a standard deviation of 13.85, while the comparison group averaged 55.05 years with a standard deviation of 14.42, a difference that did not reach statistical significance. This age matching matters because age is among the strongest predictors of severe COVID-19, and any meaningful gap in age distribution could have distorted the apparent effect of liver disease. Within the liver disease group, cirrhosis dominated the diagnostic landscape, accounting for 45.9 percent of cases, making advanced scarring of the liver the single most common underlying hepatic disorder among the affected patients.
The laboratory data revealed a striking biochemical signature distinguishing the liver disease cohort. Patients with chronic liver disease showed significantly higher serum levels of aspartate aminotransferase and alanine aminotransferase, the two canonical enzymes released when hepatocytes are injured, as well as elevated bilirubin, the pigment that accumulates when the liver’s processing capacity falters. Their prothrombin times were prolonged, indicating impaired synthesis of clotting factors by a struggling liver, and their blood urea nitrogen levels were elevated, a marker that can reflect dehydration, catabolic stress, or impaired renal perfusion, all common in decompensating cirrhotic patients. These differences were statistically significant at the conventional threshold of P less than 0.05, and together they paint a picture of patients whose hepatic reserve was already compromised before the viral infection added its own burden.
Clinical presentation also diverged between the groups in ways that carry practical implications for frontline physicians. Abdominal pain and confusion were reported more frequently among patients with chronic liver disease. Both symptoms are readily explicable by hepatic pathophysiology: abdominal pain can arise from portal hypertension, ascites stretching the peritoneum, or the capsular distension of an inflamed liver, while confusion in cirrhotic patients frequently signals hepatic encephalopathy, the neuropsychiatric syndrome caused when the failing liver fails to clear ammonia and other neurotoxic metabolites from the circulation. The overlap between encephalopathy and the confusion of severe COVID-19 hypoxia presents a genuine diagnostic challenge, and the study’s finding underscores that clinicians evaluating a confused COVID-19 patient with known liver disease must consider both mechanisms simultaneously.
The central result of the study concerns survival. After accounting for the comparison design, the researchers found that chronic liver disease was associated with higher odds of in-hospital mortality compared with the selected non-CLD comparison group. In other words, even against counterparts who were similar in age and free of other recorded chronic conditions, patients whose livers were chronically diseased died in the hospital at a meaningfully higher rate. This aligns with the mechanistic expectations that motivated the study in the first place. Patients with chronic liver disease are considered particularly vulnerable to COVID-19 because of immune dysregulation, chronic inflammation, and impaired metabolic function, a triad that leaves them less equipped to mount an effective antiviral response and more prone to the runaway inflammatory cascades that characterize severe disease.
The mechanistic plausibility of this vulnerability rests on well-characterized biology. The angiotensin-converting enzyme 2 receptor, which SARS-CoV-2 uses to enter cells, is expressed on cholangiocytes, the epithelial cells lining the bile ducts, providing a potential route for direct viral injury to the biliary tree and, indirectly, to hepatocytes. Beyond direct infection, the systemic inflammation of severe COVID-19, driven by elevated interleukin-6 and C-reactive protein, can precipitate decompensation in a cirrhotic liver that was already operating near its functional ceiling. The coagulopathy of COVID-19, marked by prolonged prothrombin times and elevated D-dimers in the sickest patients, compounds the baseline coagulation abnormalities of advanced liver disease, creating a convergent prothrombotic and prohemorrhagic hazard that neither condition alone would produce to the same degree.
Not every measured outcome differed between the groups, and the negative findings are themselves informative. The duration of hospitalization was statistically indistinguishable between patients with and without chronic liver disease, with a P value of 0.972, suggesting that among those who survived, the liver disease did not prolong the hospital stay in this cohort. The study also evaluated intensive care unit admission as an outcome, alongside demographic characteristics, clinical manifestations, laboratory parameters, and treatment outcomes, providing a broad clinical picture of how the two cohorts fared across the arc of their admissions. Analyses were performed using SPSS version 26, the standard statistical package for medical cohort studies of this scale.
The authors are careful to flag the boundaries of what their data can support. Because subgroup analyses according to cirrhosis status were not performed, no conclusions can be drawn from this cohort regarding the specific association between cirrhosis itself and clinical outcomes, even though cirrhosis was the most common underlying disorder among the liver disease patients. This is a meaningful limitation, since cirrhosis represents the extreme end of the chronic liver disease spectrum, and its specific contribution to COVID-19 mortality has been debated in the international literature. The single-center design at one hospital in Babol, and the modest sample size of 37 exposed patients, further counsel caution in generalizing the effect estimates to other populations and health care settings.
Nevertheless, the study’s practical message for clinicians is clear and actionable. A hospitalized COVID-19 patient with chronic liver disease should be recognized from the outset as belonging to a higher-risk category, warranting closer laboratory surveillance of transaminases, bilirubin, and coagulation parameters, a lower threshold for investigating altered mental status as possible encephalopathy, and heightened vigilance for the decompensation events, such as variceal bleeding, infection, and renal failure, that convert chronic hepatic disease into acute organ failure. The research was approved by the Ethics Committee of Babol University of Medical Sciences under code IR.MUBABOL.REC.1402.155, received no external funding, and was published open access on 6 October 2026, with the authors declaring no competing interests. As the pandemic’s legacy continues to be mapped across vulnerable populations, studies of this kind sharpen the clinical stratification tools that determine which patients need the most aggressive monitoring when SARS-CoV-2 arrives on the ward.
Subject of Research: The association between chronic liver disease and clinical outcomes, including in-hospital mortality, in patients hospitalized with COVID-19.
Article Title: Association of chronic liver disease with clinical outcomes and in-hospital mortality among hospitalized patients with COVID-19: a retrospective cohort study from Northern Iran
Article References: Zabihi, R., Abedi, S. H., Shirafkan, H., Dehpanah, A. A., Raei, A., Zebardast, A., & Yahyapour, Y. (2026). Association of chronic liver disease with clinical outcomes and in-hospital mortality among hospitalized patients with COVID-19: a retrospective cohort study from Northern Iran. Gut Pathogens. https://doi.org/10.1186/s13099-026-00888-4
Image Credits: AI Generated
DOI: 10.1186/s13099-026-00888-4
Keywords: COVID-19, chronic liver disease, cirrhosis, SARS-CoV-2, in-hospital mortality, clinical outcomes, retrospective cohort study, liver enzymes, hepatic encephalopathy, Iran, Gut Pathogens, coagulopathy
News Source: Drew Townsend. (October 6, 2026). Chronic Liver Disease Raises Death Risk in Hospitalized COVID-19 Patients, Iranian Cohort Finds. Scienmag.
