The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time.

We utilized the N3C level 3 data set with uncensored dates to identify all patients with chronic liver disease (CLD) with and without cirrhosis who had SARS-CoV-2 infection as of November 2023. We described the observed 30-day case fatality rate (CFR) by month of infection. We used adjusted survival analyses to calculate relative hazard of death by month of infection compared with infection at the onset of the COVID-19 pandemic.

We identified 117,811 total patients with CLD infected with SARS-CoV-2 between March 2020 and November 2023: 27,428 (23%) with cirrhosis and 90,383 (77%) without cirrhosis. The observed 30-day CFRs during the entire study period were 1.1% (1016) for patients with CLD without cirrhosis and 6.3% (1732) with cirrhosis. Observed 30-day CFRs by month of infection varied throughout the pandemic and showed a sustained downward trend since 2022. Compared with infection in Quarter 2 of 2020 (at the beginning of the pandemic), the adjusted hazards of death at 30 days for infection in Quarter 3 of 2023 were 0.20 (95% confidence interval [CI], 0.08-0.50) for patients with CLD without cirrhosis and 0.35 (95% CI, 0.18-0.69) for patients with CLD with cirrhosis.

In this N3C study, we found that the observed 30-day CFR decreased progressively for patients with CLD both with and without cirrhosis, consistent with broader trends seen in the general population.

The factors affecting the antibody responses to the ZF2001 vaccine remain unknown. To address this, we conducted a cross-sectional serological study in the real world. Adults with no prior SARS-CoV-2 infection history and received three doses of ZF2001 vaccine were invited to our study in the early stages of the COVID-19 epidemic in Chongqing between 7 April 2021 and 17 November 2021. A questionnaire survey was conducted to obtain demographic characteristics, health information, and the frequency of lifestyles at the time of enrollment. A total of 266 eligible subjects aged 18 to 86 years, with a median age of 56.00 (IQR: 34-66) participated. 68.80% of them were female. Hypertension (13.16%) and diabetes (6.02%) were common comorbidities. Serum samples were collected at one month after the third dose of ZF2001 vaccination, and serological testing was conducted using the Pseudovirus-Based Neutralization Assay. The chi-square test was employed to compare seropositivity rates, and the Mann-Whitney U test or the Kruskal-Wallis test was used to analyze the neutralizing antibodies level in stratified groups. Subsequently, univariate and multivariate linear regression analyses were conducted to identify the influencing factors. We observed that seropositivity rates was 76.32%, with 95% confidence interval (95%CI) 70.85%-81.03%, and geometric mean titer (GMT) was 120.26, with 95%CI 100.38-144.08. Age, diabetes, and frequently of alcohol were negative associations with antibody response (β = -0.2021, 95% CI: -0.2507 to -0.1535, β = -0.2873, 95% CI: -0.5590 to -0.0155, β = -0.2082, 95% CI: -0.3419 to-0.0746, P < 0.0001, P = 0.0384, P = 0.0024). Conversely, the -interval between 1 and 2 dose and frequently of tea were positive associations with antibody response (β = 0.1369, 95% CI: 0.0463 to 0.2275, β = 0.0830, 95% CI: 0.0106 to 0.1554, P = 0.0032, P = 0.0247). Overall, the ZF2001 vaccine-induced antibody response was influenced by a multifactor that may provide a reference for the development of personalized antigen vaccines and vaccination strategies in the future.

This review aimed to assess the safety and efficacy of SARS-CoV-2 vaccines in patients with chronic liver disease (CLD).

Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science were searched from 2020 to 2024. Data was extracted following Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The random-effects model (when I2 ≥ 50%) or fixed effect model (I2 < 50%) was used.

29 studies were included in this review. Compared to healthy controls (HCs), patients with CLD had a higher incidence of mild adverse events (RR = 1.60, p < 0.001), while the incidence of severe adverse events was similar (RR = 1.08, p = 0.92). Seropositivity rates of three antibodies in patients were lower than in HCs [neutralizing antibody (RR = 0.86, p = 0.002), anti-spike antibody (RR = 0.97, p = 0.06) and anti-receptor binding domain antibody (RR = 0.95, p = 0.04)]. Compared to unvaccinated patients, vaccinated patients had lower rates of SARS-CoV-2 infection, hospitalization and death (p ≤ 0.05).

SARS-CoV-2 vaccines showed good safety and efficacy in CLD patients, but antibody response appeared to be decreased. Therefore, SARS-CoV-2 vaccines and booster doses should be given priority in this vulnerable population.

Clinical practice showed that many patients with SARS-CoV-2 infection presented with long COVID syndrome in digestive system. We sought to investigate the factor affecting the incidence of long COVID syndrome in digestive system.

Patients with SARS-CoV-2 infection diagnosed at two centers of Zhongshan Hospital and one center of Shanghai Pudong Hospital from March 01, 2022 to May 31, 2022 were enrolled, collected in the hospital database, and followed up until March 30, 2023. The primary outcome of the study was the occurrence of post-acute sequelae of COVID-19 in the digestive system (long COVID syndrome). Modified Poisson regression was used to calculate the relative risk (RR). This cohort study included 494 patients with SARS-CoV-2 infection, 144 (29.1 %) patients developed liver function abnormality on admission. During the follow-up period, the primary study outcome occurred in 30 (20.8 %) of the group presenting with liver function abnormality on admission and in 20 (5.7 %) of the group without liver function abnormality on admission (adjusted, RR = 3.550, 95%CI: 2.099-6.006, P ≤ 0.001).

Our study suggests that patients with COVID-19 who experience liver function abnormality on admission have an increased risk of developing long COVID syndrome in the digestive system.

Several studies have investigated the relationship between ursodeoxycholic acid (UDCA) and COVID-19 infection. However, complex and conflicting results have generated confusion in the application of these results.

We aimed to investigate whether the association between UDCA and COVID-19 infection can also be demonstrated through the analysis of a large-scale cohort.

This retrospective study used local and nationwide cohorts, namely, the Jeonbuk National University Hospital into the Observational Medical Outcomes Partnership common data model cohort (JBUH CDM) and the Korean National Health Insurance Service claim-based database (NHIS). We investigated UDCA intake and its relationship with COVID-19 susceptibility and severity using validated propensity score matching.

Regarding COVID-19 susceptibility, the adjusted hazard ratio (aHR) value of the UDCA intake was significantly lowered to 0.71 in the case of the JBUH CDM (95% CI 0.52-0.98) and was significantly lowered to 0.93 (95% CI 0.90-0.96) in the case of the NHIS. Regarding COVID-19 severity, the UDCA intake was found to be significantly lowered to 0.21 (95% CI 0.09-0.46) in the case of JBUH CDM. Furthermore, the aHR value was significantly lowered to 0.77 in the case of NHIS (95% CI 0.62-0.95).

Using a large-scale local and nationwide cohort, we confirmed that UDCA intake was significantly associated with reductions in COVID-19 susceptibility and severity. These trends remained consistent regardless of the UDCA dosage. This suggests the potential of UDCA as a preventive and therapeutic agent for COVID-19 infection.

Three years after the beginning of the SARS-CoV-2 pandemic, the safety and efficacy of COVID-19 vaccination in liver cirrhosis (LC) patients remain controversial. We aimed to study the safety, immunological, and clinical responses of LC patients to COVID-19 vaccination.

Prospective multicentric study in adults with LC eligible for COVID-19 vaccination, without prior known infection. Patients were followed up until the timing of a booster dose, SARS-CoV-2 infection, or death. Spike-protein immunoglobulin G antibody titers for SARS-CoV-2 at 2 weeks, 3 months, and 6 months postvaccination were assessed. Antibody titers <33.8 binding antibody units (BAU)/mL were considered seronegative and <200 BAU/mL suboptimal. Postvaccination infection and its severity were registered.

We included 124 LC patients, 81% males, mean aged 61 ± 10 years, with a mean follow-up of 221 ± 26 days. Alcohol was the most common (61%) cause of cirrhosis, and 7% were under immunosuppressants for autoimmune hepatitis; 69% had portal hypertension, 42% had a previous decompensation, and 21% had a Child-Pugh-Turcotte score of B/C. The type of vaccine administrated was BNT162b2 (n = 59, 48%), ChAdOx1nCoV-19 (n = 45, 36%), mRNA-1273 (n = 14, 11%), and Ad26.COV2.S (n = 6, 5%). Eighteen percent of the patients reported adverse events after vaccination, none serious. Median [Q1; Q3] antibody titers were 1,185 [280; 2,080] BAU/mL at 2 weeks, 301 [72; 1,175] BAU/mL at 3 months, and 192 [49; 656] BAU/mL at 6 months. There were seronegative and suboptimal antibody responses in 8% and 23% of the patients at 2 weeks, 16% and 38% at 3 months, and 22% and 48% at 6 months. Older age and adenovirus vector vaccines were the only factors associated with seronegative and suboptimal responses at 2 weeks and 3 months (p < 0.05) in a multivariable logistic regression analysis. Eleven patients (9%) were infected with SARS-CoV-2 during follow-up (3.8-6.6 months postvaccination), all with mild disease. There were no differences regarding the type of vaccine, and 73% had antibody titers >200 BAU/mL at 3 months.

COVID-19 vaccines in patients with LC were safe, without serious adverse events. The humoral and clinical responses were similar to the reported for the general population. Humoral response was adversely impacted by older age and adenovirus vector vaccines and unrelated to the liver disease severity.

Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure. Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients. Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1 month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent. Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA's effectiveness in COVID-19 prevention or treatment.

COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.

Severe outcomes of COVID-19 are associated with advancing age and comorbidities. The specific aim of our study was to determine the impact of COVID-19 on the clinical course and outcome of patients with cirrhosis.

We retrieved data from VA national repository and identified patients tested for SARS-CoV-2 RNA who had cirrhosis. Each virus positive patient was propensity-matched with virus negative subjects by demographics and comorbidities. Primary endpoint was death within 30 days of COVID-19 diagnosis and secondary endpoint was hospitalization within 14 days.

Among 1,115,037 individuals tested for SARS-CoV-2 RNA, 31,680 had cirrhosis. Of those patients, 4456 virus positive patients were propensity-matched with 8752 virus negative subjects. In this cohort of 13,208, median age was 67 years and 95% were male. Most had multiple comorbidities. Alcohol use, hepatitis C and MASH were the dominant etiologies of cirrhosis. At baseline, median MELD was 6% and 21% had hepatic decompensation. Advanced age was the most significant determinant of hospitalization and mortality. Comorbidities, alcohol use and MELD increased the likelihood of hospitalization whereas SARS-CoV-2 positivity had lower Day-14 hospitalization hazard. MELD was associated with higher mortality hazard whereas vaccination reduced the hazard of hospitalization and death. SARS-CoV-2 positivity increased the hazard of death at Day-30 by 72% and at Day-90 by 26%.

Although patients with cirrhosis who developed COVID-19 were less likely to be hospitalized, they were more likely to die within 30 days compared to their virus negative counterparts. Vaccination was effective in reducing both hospitalization and death.

As part of the COVID-19 control strategy, a growing number of vaccine portfolios evolved and got fast-tracked through regulatory agencies, with a limited examination of their efficacy and safety in vulnerable populations, such as patients with chronic conditions and immunocompromised states. Patients with chronic liver disease (CLD), and cohorts post liver transplant (LT) in particular, were underrepresented in the determinant trials of vaccine development, hence the paucity of data on their efficacy and safety in published literature. This systematic review aims to examine the available evidence and ascertain the effectiveness and safety of Covid-19 vaccination in patients with CLD and those with LT.

A systematic review of PubMed (Medline), Google Scholar, Cochrane Library, and ScienceDirect from inception until 1st March 2022 was conducted. We included observational studies and assessed vaccine efficacy regarding seroconversion or immunological rate, whereas serious or significant adverse effects have been considered safety outcomes when reported.

Studies comprised 45275 patients, performed in 11 different countries. Seroconversion or immunological rate after Covid-19 vaccination was mostly the primary endpoint, whereas other endpoints like covid-19 related adverse effects were also reported. Twenty-four of the final analyzed studies are prospective cohort studies, while four are retrospective cohort studies. Twenty-one studies included patients who underwent LT and received the Covid vaccine; nine included patients who had CLD due to various etiologies. The median age range of all included patients varied from 43-69 years. All patients with LT who received at least two doses of Covid vaccine had a seroconversion rate of around 60%. Patients with CLD had a seroconversion rate of about 92% post two doses of Covid vaccination. The average seroconversion rate in post-transplant recipients was around 45% after two doses of the significant Covid vaccines: Pfizer, AstraZeneca, Moderna, and Jansen. Only two studies have reported a higher seroconversion rate of 75% and 73% after the third dose of Covid vaccine. No significant adverse effects were reported in all studies; the most commonly reported negative effect was local injection site pain.

The present systematic review, comprising real-world observational data studies, concludes that Covid-19 vaccination was associated with 92% and 60% seroconversion rates in patients with CLD and LT, respectively. No significant side effects were reported in all studies. This finding helps to resolve the uncertainty associated with Covid-19 vaccination in this cohort of patients.

The COVID-19 outbreak has had severe consequences for global public health, medical communities, and the socioeconomic status of a considerable number of countries. The emergence of COVID-19 has also significantly impacted the world of liver transplantation (LT). Studies from transplantation centers around the world have shown that LTs during the COVID-19 pandemic have been restricted because of the high risk of serious COVID-19 infection in this population. According to the Centers for Disease Control and Prevention, patients with liver disease are considered at higher risk for severe COVID-19 infection. In March 2020, the American Association for the Study of Liver Diseases recommended that LT should be limited to emergency cases. The COVID-19 treatment guidelines published by the National Institutes of Health are being constantly updated according to new epidemiology trends and treatment regimens. Immunocompromised patients have a higher risk of developing severe disease or death from COVID-19 compared with the general population. In this review, we summarize the available evidence regarding treatment guidelines and considerations for the evaluation and management of LT candidates and recipients in the era of COVID-19. In addition, we present data regarding COVID-19 among LT patients in our local transplantation center.

The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes.

The coronavirus disease 2019 (COVID-19) pandemic has had enormous implications for the care of patients with chronic liver disease (CLD), cirrhosis, and liver transplant (LT). Clinical outcomes of COVID-19 vary in patients with CLD and cirrhosis compared to healthy controls, and in patients with LT compared to patients without LT. Several special considerations apply to the approach to vaccination and treatment in patients with CLD and LT. The practice of liver transplantation has also been heavily impacted by the pandemic, including persistent reductions in living donor LT and increases in LT for an indication of alcohol-related liver disease. Recent medical society guidelines strive to standardize severe acute respiratory syndrome coronavirus 2 testing in donors and recipients and the approach to transplantation after recovered from COVID-19 infection, but certain controversies remain.

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a useful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vaccine response has been observed in liver transplant recipients, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data comparing the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavirus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospective studies are required to investigate the duration of immunity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.

Coronavirus disease 2019 (COVID-19) typically presents with fever and respiratory symptoms in children. Most children develop an asymptomatic and mild illness, with a minority requiring specialist medical care. Gastrointestinal manifestations and liver injury can also occur in children following infection. The mechanisms of liver injury may include infection following direct viral hepatic tissue invasion, immune response, or medication effects. Affected children might develop mild liver dysfunction which has a benign course in most children with no pre-existing liver disease. However, the presence of non-alcoholic fatty liver disease or other pre-existing chronic liver disorders is associated with a higher risk of developing severe COVID-19 illness with poor outcomes. On the other hand, the presence of liver manifestations is associated with the severity of COVID-19 disease and is considered an independent prognostic factor. Respiratory, hemodynamic, and nutritional supportive therapies are the mainstay of management. Vaccination of children at increased risk of developing severe COVID-19 disease is indicated. This review describes the liver manifestations in children with COVID-19, detailing its epidemiology, basic mechanisms, clinical expression, management, and prognosis in those with and without pre-existing liver disease and also children who have had earlier liver transplantation.

Studies have demonstrated that reducing farnesoid X receptor activity with ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme in human lung, intestinal and cholangiocytes organoids in vitro, in human lungs and livers perfused ex situ, reducing internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. This offers a potential novel target against coronavirus disease 2019 (COVID-19). The objective of our study was to compare the association between UDCA exposure and SARS-CoV-2 infection, as well as varying severities of COVID-19, in a large national cohort of participants with cirrhosis.

In this retrospective cohort study among participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver cohort, we compared participants with exposure to UDCA, with a propensity score (PS) matched group of participants without UDCA exposure, matched for clinical characteristics, and vaccination status. The outcomes included SARS-CoV-2 infection, symptomatic, at least moderate, severe, or critical COVID-19, and COVID-19-related death.

We compared 1607 participants with cirrhosis who were on UDCA, with 1607 PS-matched controls. On multivariable logistic regression, UDCA exposure was associated with reduced odds of developing SARS-CoV-2 infection (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.41-0.71, p < 0.0001). Among patients who developed COVID-19, UDCA use was associated with reduced disease severity, including symptomatic COVID-19 (aOR 0.54, 95% CI 0.39-0.73, p < 0.0001), at least moderate COVID-19 (aOR 0.51, 95% CI 0.32-0.81, p = 0.005), and severe or critical COVID-19 (aOR 0.48, 95% CI 0.25-0.94, p = 0.03).

In participants with cirrhosis, UDCA exposure was associated with both a decrease in SARS-CoV-2 infection, and reduction in symptomatic, at least moderate, and severe/critical COVID-19.

Coronavirus-disease-2019 (COVID-19) mRNA vaccination effectively reduces mortality and morbidity in cirrhotic patients, but the immunogenicity and safety of vaccination have been partially characterized. The study aimed to evaluate humoral response, predictive factors, and safety of mRNA-COVID-19 vaccination in cirrhotic patients compared to healthy subjects. A prospective, single-center, observational study enrolled consecutive cirrhotic patients who underwent mRNA-COVID-19 vaccination from April to May 2021. Anti-spike-protein (anti-S) and nucleocapsid-protein (anti-N) antibodies were evaluated before the first (T0) and the second (T1) doses and 15 days after completing the vaccination. An age and sex-matched healthy reference group was included. The incidence of adverse events (AEs) was assessed. In total, 162 cirrhotic patients were enrolled, 13 were excluded due to previous SARS-CoV-2 infection; therefore, 149 patients and 149 Health Care Workers (HCWs) were included in the analysis. The seroconversion rate was similar in cirrhotic patients and HCWs at T1 (92.5% vs. 95.3%, p = 0.44) and T2 (100% in both groups). At T2, anti-S-titres were significantly higher in cirrhotic patients compared to HCWs (2776.6 vs. 1756 BAU/mL, p < 0.001]. Male sex (β = -0.32 [-0.64, -0.04], p = 0.027) and past-HCV-infection (β = -0.31 [-0.59, -0.04], p = 0.029) were independent predictors of lower anti-S-titres on multiple-gamma-regression-analysis. No severe AEs occurred. The COVID-19-mRNA vaccination induces a high immunization rate and anti-S-titres in cirrhotic patients. Male sex and past-HCV infection are associated with lower anti-S-titres. The COVID-19-mRNA vaccination is safe.

The interest in vaccination efficacy and toxicity has surged following the Covid-19 pandemic. Immune responses to several vaccines have been shown to be suboptimal in patients with chronic liver disease (CLD) or post-liver transplant (LT), as a consequence of cirrhosis-associated immune dysfunction (CAID) or post-LT immunosuppression respectively. Accordingly, vaccine-preventable infections may be more common or severe than in the general population. The Covid-19 pandemic has greatly accelerated research and development into vaccination technology and platforms, which will have spillover benefits for liver patients. The aims of this review are: (i) to discuss the impact of vaccine-preventable infections on CLD and post-LT patients, (ii) to appraise current evidence supporting vaccination strategies, and (iii) to provide some insight into recent developments relevant for liver patients.

The immunogenicity and safety of vaccines against coronavirus disease 2019 (COVID-19) remain unknown in patients with a history of pulmonary tuberculosis (OPTB). Therefore, the safety and effectiveness of inactivated vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in patients with a history of PTB. The study cohort included 106 healthy controls and 93 adult patients with OPTB who received a two-dose vaccination. The study period was 21 to 105 days. Concentrations of antibodies (Abs) against receptor-binding domain (RBD) IgG and SARS-CoV-2 neutralizing Abs (NAbs) were measured, in addition to the frequencies of SARS-CoV-2-specific B and a portion T cells. The incidence of adverse events was similar between the OPTB patients and healthy controls. No severe adverse events occurred. Concentrations of Abs against RBD-IgG and CoV-2 neutralizing Abs in addition to the frequencies of RBD-specific memory B cells proportions were lower in OPTB patients than the healthy controls (all, p < 0.05), while the frequencies of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4⁺) cells were higher (p = 0.023). There was no obvious correlation between age and blood concentrations of Abs against RBD-IgG and CoV-2 neutralizing Abs, while immune responses were similar in the fibrosis and calcification groups. The period of time following full-course vaccination and lymphocyte counts were associated to anti-RBD-IgG responses. Inactivated COVID-19 vaccinations were well tolerated in OPTB patients, although immunogenicity was limited in this population. This study has been registered at ClinicalTrials.gov (NCT05043246).

Outcomes of breakthrough SARS-CoV-2 infections have not been well characterized in non-veteran vaccinated patients with chronic liver diseases (CLD). We used the National COVID Cohort Collaborative (N3C) to describe these outcomes.

We identified all CLD patients with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of January 15, 2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients. We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of 43,079 vaccinated patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) with cirrhosis. Breakthrough infection incidences were 5.4 and 4.9 per 1000 person-months for fully vaccinated CLD patients without cirrhosis and with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The 30-day outcome of mechanical ventilation or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days.

In this N3C study, breakthrough infection rates were similar among CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality for breakthrough infection among CLD patients with cirrhosis. These results provide an additional impetus for increasing vaccination uptake in CLD populations.

Few reports, all retrospective, have evaluated vaccine coverage against COVID-19 infection in cirrhotic subjects. No data are available for European Countries. We aimed to explore this topic and potential independent predictors of lack of vaccination.

Between January 1st and June 30th 2022, 1512 cirrhotic subjects of any etiology were consecutively enrolled in an observational - prospective study in 8 referral centers in Italy. Adjusted Odds Ratios (O.R.) for the association with lack of vaccination and with occurrence of breakthrough infection were evaluated by multiple logistic regression analysis.

Overall vaccine coverage was 89.7% (80% among people born abroad). Among the 1358 vaccinated people, 178 (13.1%) had a breakthrough infection; of them 12 (6.7%) were hospitalized, but none died. Independent predictors associated with lack of vaccination were birth abroad, age <65 years and lower years of schooling. Child stage B/C was the only independent predictor of breakthrough infection. Occurrence of breakthrough infection was more likely reported in subjects who received 2 doses of vaccine than in those who received 3 doses (33.9% versus 9.0%; P<0.001).

High vaccine coverage against COVID-19 infection is observed among cirrhotic subjects in Italy. Vaccine is effective in preventing severe outcomes. Three doses are more effective than two, even in cirrhotic subjects.

This large cohort study evidenced high vaccine coverage against COVID-19 infection among cirrhotic subjects in a European country and the effectiveness of vaccine in preventing severe outcomes. Three doses of vaccine are more effective than two in preventing breakthrough infection and hospitalization. Informative campaigns targeting people younger than 65 years of age and those with lower years of schooling may increase these excellent results.

Coronavirus disease-2019 (COVID-19) had become a global pandemic since March 2020. Although, the most common presentation is of pulmonary involvement, hepatic abnormalities can be encountered in up to 50% of infected individuals, which may be associated with disease severity, and the mechanism of liver injury is thought to be multifactorial. Guidelines for management in patients with chronic liver disease during COVID-19 era are being regularly updated. Patients with chronic liver disease and cirrhosis, including liver transplant candidates and liver transplant recipients are strongly recommended to receive SARS-CoV-2 vaccination because it can reduce rate of COVID-19 infection, COVID-19-related hospitalization, and mortality.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), has led to a pandemic with more than 6.5 million deaths worldwide. Patients with liver cirrhosis (PWLC) are regarded as prone to severe COVID-19. Vaccination against SARS-CoV-2 has been proven to be the most effective measure against COVID-19 and a variety of different vaccines have been approved for use; namely mRNA and vector-based, inactivated, whole virion, and protein subunit vaccines. Unfortunately, only a small number of PWLC were included in phase I-III vaccine trials, raising concerns regarding their efficacy and safety in this population. The authors, in this review, present available data regarding safety and efficacy of anti-SARS-CoV-2 vaccination in PWLC and discuss post-vaccination antibody responses. Overall, all vaccines seem to be extremely safe, with only a few and insignificant adverse events, and efficient, leading to lower rates of hospitalization and COVID-19-related mortality. T- and B-cell responses, on the other hand, remain an enigma, especially in patients with decompensated disease, since these patients show lower titers of anti-SARS-CoV-2 antibodies in some studies, with a more rapid waning. However, this finding is not consistent, and its clinical impact is still undetermined.

Patients with cirrhosis have a higher risk of severe COVID-19 and mortality and are high-priority patients for vaccination. However, cirrhotics were excluded from the phase 2/3 vaccine trials. Hence, we aimed to assess the antibody response and safety of Covishield (ChAdOx1nCoV-19) among patients with cirrhosis.

Patients who attended the tele-hepatology services at our institute from March 2020 to June 2021 and diagnosed with cirrhosis as per their medical records were telephonically interviewed in July 2021 using a pre-specified questionnaire. Patients who had completed 2 doses of ChAdOx1-nCOV (with the 2^nd dose administered at least 2 weeks back) and without history of documented COVID-19 infection (pre- or post-vaccination) were tested for antibodies against the spike protein. Seropositive patients were divided into high, moderate, and low antibody responses based on the signal/cut-off.

We interviewed 784 patients with cirrhosis. At least 1 dose of ChAdOx1-nCOV was received by 231 patients among whom 134 (58%) had received 2 doses. Documented COVID-19 was reported in 3.9% patients who received at least 1 dose of ChAdOx1-nCOV including breakthrough infections in 3.7% patients vaccinated with 2 doses. Local and systemic adverse events were reported by 42% and 22.1% patients. None developed anaphylaxis, acute decompensation, acute-on-chronic liver failure, or other serious adverse events requiring hospitalization. Seroconversion was documented in 81 (92%) out of 88 patients. No difference was observed in level of antibody response between patients with compensated and decompensated cirrhosis (p = 0.12).

Our preliminary data suggest that ChAdOx1-nCOV is safe with high seroconversion rates in patients with cirrhosis.

The coronavirus disease-2019 (COVID-19) pandemic has had a large impact on patients with chronic liver disease (CLD) and liver transplantation (LT) recipients. Patients with advanced CLD are at a significantly increased risk of poor outcomes in the setting of severe acute respiratory syndrome coronavirus 2 infection. The pandemic has also considerably altered the management and care that is provided to patients with CLD, pre-LT patients, and LT recipients. Vaccination against COVID-19 protects patients with CLD and LT recipients from adverse outcomes and is safe in these patients; however, vaccine efficacy may be reduced in LT recipients and other immunosuppressed patients.

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two years, many studies have been published suggesting that excessive drinking not only worsens the course of an acute respiratory distress syndrome caused by the SARS-CoV-2 virus but can also exacerbate post-COVID-19 syndrome. Despite all sorts of online speculation, there is no specific scientific data on alcohol-induced complications after vaccination in the literature. Most of the published vaccine clinical trials do not include groups of patients with a history of alcohol-use disorders. This review analyzed the well-known and new mechanisms of action of COVID-19 vaccines on the immune system and the effects of alcohol and its metabolites on these mechanisms.

The coronavirus disease 2019 pandemic has significantly impacted liver tran splantation worldwide, leading to major effects on the transplant process, including the pretransplant, perioperative, and post-transplant periods. It is believed that patients with chronic liver disease, especially those with cirrhosis, have a higher risk of complications from coronavirus disease 2019 infection compared to the general population. However, evaluation of coronavirus disease 2019 effects on liver transplant patients has not uniformly demonstrated worse outcomes. Nonetheless, the pandemic created significant challenges and restrictions on transplant policies and organ allocation.

The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.

SARS-CoV-2 vaccinations were found to be highly effective in phase 3 clinical trials. However, these trials have not reported data regarding the subgroup of liver disease or excluded patients with liver disease. The effectiveness of COVID-19 vaccines among liver cirrhosis (LC) patients is unclear. We conducted this meta-analysis to assess the effectiveness of SARS-CoV-2 vaccination in LC patients. A comprehensive literature search was conducted to include all the relevant studies that compared the outcomes of LC patients who received SARS-CoV-2 vaccines vs. unvaccinated patients. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method within a random-effect model. Four studies with 51,834 LC patients (20,689 patients received at least one dose vs 31,145 were unvaccinated) were included. COVID-19-related complications, including hospitalization (RR 0.73, 95% CI 0.59-0.91, P = 0.004), mortality (RR 0.29, 95% CI 0.16-0.55, P = 0.0001), and need for invasive mechanical ventilation (RR 0.29, 95% CI 0.11-0.77, P = 0.01), were significantly lower in the vaccinated group compared to the unvaccinated group. SARS-CoV-2 vaccination in LC patients reduced COVID-19-related mortality, intubation, and hospitalization. SARS-CoV-2 vaccination is highly effective in LC. Further prospective studies, preferably randomized controlled trials, are necessary to validate our findings and determine which vaccine is superior in patients with LC.

Immunity to SARS-CoV-2 can be infection or vaccine-induced. Cirrhosis is associated with vaccine hyporesponsiveness, but whether there is decreased immunity after SARS-CoV-2 infection in unvaccinated patients with cirrhosis is unknown.The objective of our study was to compare infection-induced and vaccine-induced immunity against COVID-19 among patients with cirrhosis.

This was a retrospective cohort study among US Veterans with cirrhosis between November 27, 2020, and November 16, 2021, comparing a vaccine-induced immunity group, defined as participants without a documented SARS-CoV-2 infection but fully vaccinated with two doses of an mRNA vaccine, and infection-associated immunity group, defined as unvaccinated participants who had a positive SARS-CoV-2 polymerase chain reaction (PCR). Both groups were propensity score matched for observed characteristics, including location, and the date of the immunity acquiring event, to control for the community prevalence of COVID-19 variants. The outcome was a positive SARS-CoV-2 PCR more than 60 days after previous infection in the infection-induced, or after full vaccination in the vaccine-induced immunity group.

We compared 634 participants in the infection-induced immunity group with 27,131 participants in the vaccine-induced immunity group using inverse propensity of treatment weighting. Vaccine-induced immunity was associated with a reduced odds of developing SARS-CoV-2 infection (adjusted hazard ratio [aHR], 0.18; 95% confidence interval [CI], 0.16-0.20, p < 0.0001). On multivariable logistic regression, vaccine-induced immunity was associated with reduced odds of developing symptomatic (adjusted odds ratio [aOR], 0.36; 95% CI, 0.33-0.41, p < 0.0001), moderate/severe/critical (aOR, 0.27; 95% CI, 0.22-0.31, p < 0.0001), and severe or critical COVID-19 (aOR, 0.20; 95% CI, 0.16-0.26, p < 0.001), compared with infection-induced immunity.

In participants with cirrhosis, vaccine-induced immunity is associated with reduced risk of developing COVID-19, compared with infection-induced immunity.

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.46-0.93), cancer (OR: 0.65; 95% CI: 0.42-0.99), and diabetes (OR: 0.50; 95% CI: 0.28-0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11-0.76), cancer (OR: 0.38; 95% CI: 0.23-0.62), and diabetes (OR: 0.37; 95% CI: 0.20-0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases.

Various vaccines against severe acute respiratory syndrome coronavirus 2 have been developed in response to the coronavirus disease 2019 (COVID-19) global pandemic, several of which are highly effective in preventing COVID-19 in the general population. Patients with chronic liver diseases (CLDs), particularly those with liver cirrhosis, are considered to be at a high risk for severe COVID-19 and death. Given the increased rates of disease severity and mortality in patients with liver disease, there is an urgent need to understand the efficacy of vaccination in this population. However, the data regarding efficacy and safety of COVID-19 vaccination in patients with CLDs is limited. Indeed, several organ-specific or systemic immune-mediated side effects following COVID-19 vaccination, including liver injury similar to autoimmune hepatitis, have been recently reported. Although the number of cases of vaccine-related liver injury is increasing, its frequency, clinical course, and mechanism remain unclear. Here, we review the current findings on COVID-19 vaccination and liver disease, focusing on: (1) The impact of COVID-19 in patients with CLD; (2) The efficacy, safety, and risk-benefit profiles of COVID-19 vaccines in patients with CLD; and (3) Liver injury following COVID-19 vaccination.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions.

Studies have shown that patients with chronic liver disease are at a higher risk of contracting novel coronavirus pneumonia than healthy individuals, and many guidelines state that patients with chronic liver disease should be prioritized for COVID-19 vaccination, but there are a few studies on its safety in CLD patients. We aimed to evaluate the safety of the inactivated COVID-19 vaccine in patients with chronic liver disease, and the effect of anxiety on adverse reactions. A questionnaire survey for self-administered post-vaccination adverse reaction monitoring was conducted from June 17, 2021, to August 11, 2021, in patients with chronic liver disease attending a tertiary care hospital in Taizhou, China. We analyzed the data from of a total of 160 participants who scanned the QR code on social media to respond to the questionnaire. The overall incidence of adverse reactions after COVID-19 vaccination in patients with chronic liver disease was 44.4% (71/160), and the most common adverse reaction was local injection site reaction, accounting for 80.3% of adverse reactions (57/71). No serious adverse reactions were reported. Approximately 53.1% of the patients had anxiety about vaccination, and 51.8% of those who felt anxious reported adverse reactions. The safety of COVID-19 vaccination in patients with chronic liver disease is good, and there is a strong association between adverse reactions and vaccine anxiety. Pre-vaccination education for patients with vaccine anxiety and psychological counseling may reduce reports of adverse reactions and improve patients' confidence in the vaccine.