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Clinical Impact of COVID-19 on Liver Diseases

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (25 July 2023) | Viewed by 20653

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Dr. Maria Guarino

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Gastroenterology and Hepatology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy
Interests: liver transplantation; hepatocellular carcinoma; cirrhosis; hepatitis C; hepatitis B; portal hypertension; chronic liver disease

Special Issue Information

Dear Colleagues,

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, rapidly spread in the first months of 2020, becoming a public health matter of pandemic status presenting several unforeseen challenges to health care systems worldwide. By the end of 2020, different vaccines for COVID-19 had been approved. Common risk factors consistently associated with severe COVID-19 are now well established and include advancing age, male sex, and a burden of comorbidities, including obesity, diabetes and chronic liver diseases (CLD). Additionally, the negative effects COVID-19 often involved liver, not only in subjects with pre-existing CLD, but also in healthy subjects, due to the hepatotropism of SARS-CoV-2. Furthermore, it has been well demonstrated that the onset of various autoimmune diseases (including autoimmune liver diseases) could be associated to SARS-CoV-2, probably due to molecular mimicry and hyperstimulation of the immune system. While knowledge on COVID-19 evolution, clinical manifestations, and optimal management is progressively increasing, treatment guidelines are difficult to standardize when taking into account special populations like patients with CLD or liver transplant recipients. Understanding the natural history of COVID-19 in these patients as well as the immunogenicity and effectiveness of SARS-CoV-2 vaccination across different etiologies and across the full spectrum of liver disease severity is, therefore, paramount. The aim of this Special Issue is to provide an overview of recent advances in the field of COVID-19 and CLD. Therefore, researchers in the field of Hepatology are encouraged to submit an original article or review to this Special Issue (case reports and short reviews will not be considered).

Dr. Maria Guarino
Guest Editor

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Keywords

COVID-19
vaccination
liver transplantation
hepatocellular carcinoma
cirrhosis
hepatitis C
hepatitis B
portal hypertension
chronic liver disease

Published Papers (9 papers)

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Research

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10 pages, 1249 KiB

Open AccessArticle

The Liver Can Deliver: Utility of Hepatic Function Tests as Predictors of Outcome in COVID-19, Influenza and RSV Infections

by Einat Ritter, Eden Shusterman, Lior Prozan, Orli Kehat, Ahuva Weiss Meilik, Oren Shibolet and Jacob Nadav Ablin

J. Clin. Med. 2023, 12(9), 3335; https://doi.org/10.3390/jcm12093335 - 08 May 2023

Viewed by 1590

Abstract

Background: liver test abnormalities have been described in patients with Coronavirus-2019 (COVID-19), and hepatic involvement may correlate with disease severity. With the relaxing of COVID-19 restrictions, seasonal respiratory viruses now circulate alongside SARS-CoV-2. Aims: we aimed to compare patterns of abnormal liver function tests in patients suffering from COVID-19 infection and seasonal respiratory viruses: respiratory syncytial virus (RSV) and influenza (A and B). Methods: a retrospective cohort study was performed including 4140 patients admitted to a tertiary medical center between 2010–2020. Liver test abnormalities were classified as hepatocellular, cholestatic or mixed type. Clinical outcomes were defined as 30-day mortality and mechanical ventilation. Results: liver function abnormalities were mild to moderate in most patients, and mainly cholestatic. Hepatocellular injury was far less frequent but had a strong association with adverse clinical outcome in RSV, COVID-19 and influenza (odds ratio 5.29 (CI 1.2–22), 3.45 (CI 1.7–7), 3.1 (CI 1.7–6), respectively) COVID-19 and influenza patients whose liver functions did not improve or alternatively worsened after 48 h had a significantly higher risk of death or ventilation. Conclusion: liver function test abnormalities are frequent among patients with COVID-19 and seasonal respiratory viruses, and are associated with poor clinical outcome. The late liver tests’ peak had a twofold risk for adverse outcome. Though cholestatic injury was more common, hepatocellular injury had the greatest prognostic significance 48 h after admission. Our study may provide a viral specific auxiliary prognostic tool for clinicians facing patients with a respiratory virus. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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11 pages, 781 KiB

Open AccessArticle

Safety and Immunogenicity of Anti-SARS-CoV-2 Booster Dose in Patients with Chronic Liver Disease

by Valentina Cossiga, Mario Capasso, Maria Guarino, Ilaria Loperto, Stefano Brusa, Francesco Maria Cutolo, Maria Rosaria Attanasio, Raffaele Lieto, Giuseppe Portella and Filomena Morisco

J. Clin. Med. 2023, 12(6), 2281; https://doi.org/10.3390/jcm12062281 - 15 Mar 2023

Cited by 5 | Viewed by 1153

Abstract

The low response to vaccines is a well-known problem in cirrhosis. We evaluated the safety and immunogenicity of booster doses in patients with chronic liver disease (CLD), comparing the humoral response in cirrhotic vs. non-cirrhotic patients, and the impact of different factors on immune response. From September 2021 to April 2022, outpatients with CLD who completed the primary vaccination course and the booster dose against SARS-CoV-2 were enrolled. Blood samples were collected after second and third doses for detecting anti-spike protein IgG. We enrolled 340 patients; among them, 91 subjects were cirrhotic. After primary vaccination course, 60 (17.6%) patients did not develop a positive antibody titer, without significant differences between cirrhotic and non-cirrhotic patients (p = 0.076); most of them (88.3%) developed it after booster dose. At multivariable analysis, factors associated with higher humoral response after booster dose were only porto-sinusoidal vascular disorder (p = 0.007) as an etiology of CLD and the use of the mRNA-1273 vaccine (p = 0.001). In conclusion, in patients with CLD, a booster dose against SARS-CoV-2 induces an excellent immunogenicity and leads to an adequate antibody response. Cirrhosis is not associated with a worse humoral response, compared to patients with non-cirrhotic CLD. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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14 pages, 1229 KiB

Open AccessArticle

Evaluation of FIB-4, NFS, APRI and Liver Function Tests as Predictors for SARS-CoV-2 Infection in the Elderly Population: A Matched Case-Control Analysis

by Mirela Loredana Grigoras, Ioana Mihaela Citu, Cosmin Citu, Veronica Daniela Chiriac, Florin Gorun, Mihaela Codrina Levai, Diana Manolescu, Ovidiu Rosca, Felix Bratosin, Srivathsava Gurumurthy, Prima Hapsari Wulandari and Octavian Marius Cretu

J. Clin. Med. 2022, 11(17), 5149; https://doi.org/10.3390/jcm11175149 - 31 Aug 2022

Cited by 10 | Viewed by 1762

Abstract

Several investigations have revealed that COVID-19 causes a significant death rate due to acute respiratory distress syndrome, alterations in the quantity of ACE2 receptor expression, or the intensity of cytokine storm. Similarly, patients with hepatic impairment that are co-infected with SARS-CoV-2 are more likely to display upregulations of ACE2 receptors and cytokine storm overload, which exacerbates hepatic impairment, potentially increasing the death rate. Moreover, it is expected that the aging population develops a higher degree of hepatic fibrosis in association with other comorbid conditions that are likely to influence the course of COVID-19. Therefore, this research was developed to describe the differences in liver test parameters in elderly individuals with COVID-19 in relation to other inflammatory markers and outcomes. This current observational single-center research followed a case-control design of elderly patients hospitalized for SARS-CoV-2 infection. The research was conducted at a tertiary emergency hospital in western Romania during a two-year period. There were 632 patients included in the analysis that were split into two equal groups matched 1:1 based on gender and body mass index. Three hundred sixteen patients made the group of cases with COVID-19 patients older than 65 years, while the other half were the 316 patient controls with COVID-19 that were younger than 65 years old. Disease outcomes showed a higher prevalence of ICU admissions (22.8% vs. 12.7%, p-value < 0.001) and in-hospital mortality (17.1% vs. 8.9%, p-value = 0.002) in the group of cases. Specific and non-specific liver biomarkers were identified as risk factors for mortality in the elderly, such as ALP (OR = 1.26), LDH (OR = 1.68), AST (OR = 1.98), and ALT (OR = 2.34). Similarly, patients with APRI and NFS scores higher than 1.5 were, respectively, 2.69 times and, 3.05 times more likely to die from COVID-19, and patients with FIB-4 scores higher than 3.25 were 3.13 times more likely to die during hospitalization for SARS-CoV-2 infection. Our research indicates that abnormally increased liver biomarkers and high liver fibrosis scores are related to a worse prognosis in SARS-CoV-2 infected individuals. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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13 pages, 1020 KiB

Open AccessArticle

Centralization of Major Trauma Influences Liver Availability for Transplantation in Northern Italy: Lesson Learned from COVID-19 Pandemic

by Michele Altomare, Andrea Chierici, Francesco Virdis, Andrea Spota, Stefano Piero Bernardo Cioffi, Shir Sara Bekhor, Luca Del Prete, Elisa Reitano, Marco Sacchi, Federico Ambrogi, Osvaldo Chiara and Stefania Cimbanassi

J. Clin. Med. 2022, 11(13), 3658; https://doi.org/10.3390/jcm11133658 - 24 Jun 2022

Cited by 1 | Viewed by 1224

Abstract

Background: During the COVID-19 pandemic, the centralization of patients allowed trauma and transplants referral centers to continue their routine activity, ensuring the best access to health care. This study aims to analyze how the centralization of trauma is linked with liver allocation in Northern Italy. Methods: Cluster analysis was performed to generate patient phenotype according to trauma-related variables. Comparison between clusters was performed to evaluate differences in damage control strategy procedures (DCS) performed and the 30-day graft dysfunction. Results: During the pandemic period, the centralization of major trauma has deeply impaired the liver procurement and allocation between the transplant centers in the metropolitan area of Milan (Niguarda: 22 liver procurement; other transplant centers: 2 organ procurement). Two clusters were identified the in Niguarda’s series: cluster 1 is represented by 17 (27.4%) trauma donors, of which 13 (76.5%) were treated with DCS procedures, and 4 (23.5%) did not; cluster 2 is represented by 45 trauma donors (72.6%), of which 22 (48.8%) underwent DCS procedures. A significant difference was found in the number of DCS procedures performed between clusters (3.18 ± 2.255 vs. 1.11 ± 1.05, p = 0.0001). Comparative analysis did not significantly differ in the number of transplanted livers (cluster1/cluster2 94.1%/95.6% p = 0.84) and the 30-day graft dysfunction rate (cluster1/cluster2 0.0%/4.8% p = 0.34). Conclusions: The high level of care guaranteed by first-level trauma centers could reduce the loss of organs suitable for donation, maintaining the good outcomes of transplanted ones, even in case of multiple organ injuries. The pandemic period underlined that the centralization of major trauma impairs the liver allocation between transplant centers. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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10 pages, 1988 KiB

Open AccessArticle

Laboratory Profile of COVID-19 Patients with Hepatitis C-Related Liver Cirrhosis

by Bianca Cerbu, Mirela Loredana Grigoras, Felix Bratosin, Iulia Bogdan, Cosmin Citu, Adrian Vasile Bota, Madalina Timircan, Melania Lavinia Bratu, Mihaela Codrina Levai and Iosif Marincu

J. Clin. Med. 2022, 11(3), 652; https://doi.org/10.3390/jcm11030652 - 27 Jan 2022

Cited by 15 | Viewed by 2143

Abstract

Patients with cirrhosis are known to have multiple comorbidities and impaired organ system functioning due to alterations caused by chronic liver failure. In the past two years, since the COVID-19 pandemic started, several studies have described the affinity of SARS-CoV-2 with the liver and biliary cells. Considering hepatitis C as a significant independent factor for cirrhosis in Romania, this research was built on the premises that this certain group of patients is susceptible to alterations of their serum parameters that are yet to be described, which might be useful in the management of COVID-19 in these individuals. A retrospective cohort study was developed at a tertiary hospital for infectious disease in Romania, which included a total of 242 patients with hepatitis C cirrhosis across two years, out of which 46 patients were infected with SARS-CoV-2. Stratification by patient weight and COVID-19 status identified several important laboratory serum tests as predictors for acute-on-chronic liver failure and risk for intensive care unit admission. Thus, white blood cell count, lymphocyte count, ferritin, hypoglycemia, prothrombin time, and HCV viral load were independent risk factors for ACLF in patients with COVID-19. High PT, creatinine, BUN, and HCV viral load were the strongest predictors for ICU admission. Inflammatory markers and parameters of gas exchange were also observed as risk factors for ACLF and ICU admission, including procalcitonin, CRP, IL-6, and D-dimers. Our study questions and confirms the health impact of COVID-19 on patients with cirrhosis and whether their laboratory profile significantly changes due to SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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15 pages, 1179 KiB

Open AccessArticle

Liver Injury and Elevated FIB-4 Define a High-Risk Group in Patients with COVID-19

by Dana Crisan, Lucretia Avram, Cristiana Grapa, Alexandra Dragan, Dan Radulescu, Sorin Crisan, Alin Grosu, Valentin Militaru, Elena Buzdugan, Laurentiu Stoicescu, Liliana Radulescu, Felix Ciovicescu, Delia Bunea Jivanescu, Oana Mocan, Bogdan Micu, Valer Donca, Luminita Marinescu, Antonia Macarie, Marina Rosu, Andrada Nemes and Rares Craciun Show full author list Hide full author list

J. Clin. Med. 2022, 11(1), 153; https://doi.org/10.3390/jcm11010153 - 28 Dec 2021

Cited by 13 | Viewed by 1815

Abstract

Liver involvement in Coronavirus Disease 2019 (COVID-19) has been widely documented. However, data regarding liver-related prognosis are scarce and heterogeneous. The current study aims to evaluate the role of abnormal liver tests and incidental elevations of non-invasive fibrosis estimators on the prognosis of hospitalized COVID-19 patients. We conducted a retrospective cohort study to investigate the impact of elevated liver tests, non-invasive fibrosis estimators (the Fibrosis-4 (FIB-4), Forns, APRI scores, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio), and the presence of computed tomography (CT)-documented liver steatosis on mortality in patients with moderate and severe COVID-19, with no prior liver disease history. A total of 370 consecutive patients were included, of which 289 patients (72.9%) had abnormal liver biochemistry on admission. Non-survivors had significantly higher FIB-4, Forns, APRI scores, and a higher AST/ALT ratio. On multivariate analysis, severe FIB-4 (exceeding 3.25) and elevated AST were independently associated with mortality. Severe FIB-4 had an area under the receiver operating characteristic (AUROC) of 0.73 for predicting survival. The presence of steatosis was not associated with a worse outcome. Patients with abnormal liver biochemistry on arrival might be susceptible to a worse disease outcome. An FIB-4 score above the threshold of 3.25, suggestive of the presence of fibrosis, is associated with higher mortality in hospitalized COVID-19 patients. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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Review

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12 pages, 661 KiB

Open AccessReview

Liver Injury Associated with COVID-19 Infection: Pathogenesis, Histopathology, Prognosis, and Treatment

by Noha Mousaad Elemam, Iman M. Talaat, Azzam A. Maghazachi and Maha Saber-Ayad

J. Clin. Med. 2023, 12(5), 2067; https://doi.org/10.3390/jcm12052067 - 06 Mar 2023

Cited by 7 | Viewed by 4160

Abstract

Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world’s regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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16 pages, 1024 KiB

Open AccessReview

Impact of SARS-CoV-2 Pandemic on the Management of Patients with Hepatocellular Carcinoma

by Maria Guarino, Valentina Cossiga, Mario Capasso, Chiara Mazzarelli, Filippo Pelizzaro, Rodolfo Sacco, Francesco Paolo Russo, Alessandro Vitale, Franco Trevisani, Giuseppe Cabibbo and on behalf of the Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group

J. Clin. Med. 2022, 11(15), 4475; https://doi.org/10.3390/jcm11154475 - 31 Jul 2022

Cited by 7 | Viewed by 2105

Abstract

Worldwide, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) significantly increases mortality and morbidity. The Coronavirus Disease 2019 (COVID-19) outbreak has had a considerable impact on healthcare systems all around the world, having a significant effect on planned patient activity and established care pathways, in order to meet the difficult task of the global pandemic. Patients with hepatocellular carcinoma (HCC) are considered a particularly susceptible population and conceivably at increased risk for severe COVID-19 because of two combined risk factors: chronic advanced liver disease and HCC itself. In these challenging times, it is mandatory to reshape clinical practice in a prompt way to preserve the highest standards of patient care and safety. However, due to the stay-at-home measures instituted to stop the spread of COVID-19, HCC surveillance has incurred a dramatic drop, and care for HCC patients has been rearranged by refining the algorithm for HCC treatment to the COVID-19 pandemic, permitting these patients to be safely managed by identifying those most at risk of neoplastic disease progression. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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8 pages, 244 KiB

Open AccessReview

COVID-19 and Autoimmune Liver Diseases

by Annarosa Floreani and Sara De Martin

J. Clin. Med. 2022, 11(10), 2681; https://doi.org/10.3390/jcm11102681 - 10 May 2022

Cited by 13 | Viewed by 3458

Abstract

SARS-CoV-2 infection can trigger autoimmune responses, either by a systemic hyperstimulation of the immune system or molecular mimicry (or both). We here summarize the current knowledges about autoimmune liver diseases (AILDs) and COVID-19, focusing on (a) the risk of SARS-CoV-2 infection in patients affected by AILDs and/or under pharmacological treatment with immunosuppressants; (b) the capability of vaccination against SARS-CoV-2 to trigger autoimmune responses in the liver; and (c) the efficacy of vaccines against SARS-CoV-2 in patients with AILDs. Although unconclusive results have been obtained regarding the risk of being infected by SARS-CoV-2, generally indicating that all patients with chronic liver diseases have the same risk, irrespective of the etiology, the use of immunosuppressants in patients with AILDs seems to be correlated to COVID-19 severity. Few cases of autoimmune hepatitis (AIH) after SARS-CoV-2 vaccination have been reported, all characterized by a complete remission upon steroid treatment, but further evidence is needed to demonstrate the causality assessment. Humoral responses have been observed in patients with AILDs upon vaccination. In conclusion, the link between SARS-CoV-2 infection and AILDs is far to be completely elucidated. In these patients, the use of immunosuppressants has been correlated to an increase of disease severity and lower levels of antibodies upon vaccination. Full article

(This article belongs to the Special Issue Clinical Impact of COVID-19 on Liver Diseases)

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