Patients with cirrhosis and liver transplant recipients are at increased risk of infections. Malnutrition, multiple hospital admissions, immune dysfunction related to cirrhosis, and immunosuppressive agents used for liver transplantation predispose the recipient to various life-threatening infections. Some of these infections are preventable with vaccines. With the COVID-19 pandemic, there has been an accelerated research in vaccination technology and platforms, which in turn may also improve awareness of physicians regarding this healthy and often ignored aspect of management of patients with cirrhosis and transplant recipients. The organ transplant candidates should complete the recommended vaccination schedule as early as possible (especially patients with compensated cirrhosis) or at least during their pretransplant work-up so as to prevent or reduce the severity of various infections.

The immunogenicity of COVID-19 vaccines in patients with liver cirrhosis remains largely unknown. The purpose of this meta-analysis was to investigate the immunogenicity of COVID-19 vaccines in patients with cirrhosis and compare the humoral and cellular immune responses following complete COVID-19 vaccination between cirrhosis patients and healthy controls. A systematic literature search was conducted in PubMed, EMBASE, and Web of Science from 1 January 2020 to 22 August 2023. Sixteen studies with 2127 cirrhosis patients were included. The pooled seroconversion rate in patients with cirrhosis following complete COVID-19 vaccination was 92.4% (95% CI, 86.2%-96%, I2 = 90%) with significant between-study heterogeneity. Moreover, COVID-19 vaccination elicited a higher humoral immune response in patients of compensated cirrhosis as compared with decompensated cirrhosis (RR = 1.069, 95% CI, 1.011-1.131, I2 = 17%, p = .019). Additionally, 10 studies were included for comparison analysis of seroconversion rate between cirrhosis patients and healthy controls. The results showed that the seroconversion rate in patients with cirrhosis was slightly lower compared with healthy controls (RR = 0.972, 95% CI, 0.955-0.989, I2 = 66%, p = .001). Meanwhile, the pooled RR of cellular immune response rate for cirrhosis patients vs. healthy controls was 0.678 (95% CI, 0.563-0.817, I2 = 0, p < .0001). Our meta-analysis demonstrated that COVID-19 vaccination elicited diminished humoral and cellular immune responses in patients of cirrhosis. Patients with cirrhosis particularly decompensated cirrhosis who have completed full-doses of COVID-19 vaccination should receive continuous attention and preemptive measures.

The global pandemic caused by the highly contagious SARS-CoV-2 virus led to the emergency approval of COVID-19 vaccines to reduce rising morbidity and mortality. However, limited research exists on evaluating the impact of these vaccines on immunocompromised individuals, such as recipients of living donor liver transplantation, highlighting the need for further studies to better understand their effectiveness in this specific population.

From June 2021, we followed up on the effectiveness of the vaccine for patients taking immunosuppressive drugs after living-donor liver transplantation (LDLT). A total of 105 immunocompromised individuals participated, of which 50 patients with hepatitis B were taking antiviral drugs. Patients were assessed to analyze how the combination of immunosuppressive and antiviral drugs affected the efficacy of the BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 COVID-19 vaccines.

Before and after the vaccinations, patients were monitored to establish differences between immunosuppressed patients and those additionally taking antiviral drugs. In immunocompromised patients taking antiviral drugs for hepatitis B, we confirmed that the effect of the COVID-19 vaccine was reduced when compared to immunocompromised patients. Interestingly, 23 patients (11 without and 12 additionally with hepatitis B drug administration) encountered breakthrough infections, and although there was a minor discrepancy in vaccine efficacy among the patients taking antiviral drugs for hepatitis B, it did not reach statistical significance.

Additional COVID-19 vaccination is recommended for patients taking immunosuppressive drugs and hepatitis B antiviral drugs after LDLT.

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.

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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) patients are at an elevated risk of developing severe coronavirus disease 2019 (COVID-19). The objective of this study was to assess antibody responses and safety profiles six months after the third dose of the inactivated acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in MASLD patients.

This study included MASLD patients and healthy volunteers without a history of SARS-CoV-2 infection. Blood samples were collected six months after receiving the third dose of the inactivated vaccine to measure the levels of neutralizing antibodies (NAbs) and anti-spike IgG antibodies against SARS-CoV-2.

A total of 335 participants (214 MASLD patients and 121 healthy volunteers) were enrolled. The seroprevalence of NAb was 61.7% (132 of 214) in MASLD patients and 74.4% (90 of 121) in healthy volunteers, which was a significant difference (p = 0.018). Statistically significant differences in IgG seroprevalence were also observed between MASLD patients and healthy volunteers (p = 0.004). Multivariate analysis demonstrated that the severity of MASLD (OR, 2.97; 95% CI, 1.32-6.68; p = 0.009) and age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.004) were independent risk factors for NAb negativity in MASLD patients. Moderate/severe MASLD patients had a lower NAb seroprevalence than mild MASLD patients (45.0% vs. 65.5%, p = 0.016).

Lower antibody responses were observed in MASLD patients six months after their third dose of the inactivated vaccine than in healthy volunteers, providing further assistance in monitoring patients who are more vulnerable to hypo-responsiveness to SARS-CoV-2 vaccines.

Patients with liver cirrhosis, due to their weakened innate and adaptive immunity, are more prone to frequent and severe vaccine-preventable infections. Moreover, impaired adaptive immunity results in a limited antibody response to vaccines. Despite this suboptimal antibody response, vaccines have proven to be very effective in reducing severe outcomes and deaths in these patients. In the Western world, regulatory authorities and scientific liver societies (e.g., AASLD and EASL) have recommended vaccinations for cirrhotic patients. However, despite these strong recommendations, vaccine coverage remains suboptimal. Improving vaccine effectiveness and safety information, providing comprehensive counseling to patients, fact-checking to combat fake news and disinformation and removing barriers to vaccination for disadvantaged individuals may help overcome the low coverage rate. In view of this, vaccines should be administered early in the course of chronic liver diseases, as their efficacy declines with the increasing severity of the disease.

The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections.

In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed.

Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients.

Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics.

We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms.

We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.

The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID-19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA-1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti-S-IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti-S-IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti-S-IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non-decompensation and 91.3% non-liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non-active HCC and 94.7% non-HCC, p < 0.001). Receiving the MMM booster regimen (OR = 10.67, 95% CI 5.20-21.91, p < 0.001) increased the odds of having significant antibody activity compared with the AZAZBNT booster regimen. Patients with active HCC had a reduced immune response to the third COVID-19 vaccine booster. These findings underscore the importance of booster vaccinations, especially in immunocompromised patients, with superior efficacy observed with the homologous mRNA-1273 regimen.

Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19.

The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness.

PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings.

SARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population.

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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.

Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.

This study aimed to evaluate the antibody and cellular responses to different coronavirus 2019 (COVID-19) vaccination regimens in patients with cirrhosis and to assess the antibody response after a vaccine booster. We conducted a prospective observational study of 89 patients with cirrhosis and 41 healthy volunteers who received two COVID-19 vaccine doses. Next, we prospectively evaluated 24 patients with cirrhosis who received a booster COVID-19 vaccine dose. In both studies, blood samples were collected before and 4 weeks after vaccination, and anti-spike receptor-binding domain protein IgG levels, T-cell phenotypes, and effector functions were assessed. The heterologous vaccine regimen (CoronaVac [SV]/AstraZeneca [AZ]) produced a better antibody response and CD4+IFNg+ T cell response compared to homogeneous vaccine regimens. The antibody response after the second dose of the vaccine was similar in patients with cirrhosis and healthy volunteers. Patients who received a booster dose of the mRNA vaccine had significantly increased antibody titers compared to those who received the AZ vaccine. In patients with cirrhosis, heterologous vaccination with SV/AZ resulted in a better immune response than the AZ/AZ and SV/SV regimens. Moreover, a booster dose of the mRNA vaccine led to a greater increase in antibody titers compared to the AZ vaccine.

Patients with chronic liver disease (CLD) are at a greater risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. This study investigated the antibody response to inactivated SARS-CoV-2 vaccination in a long-term prospective cohort of CLD patients. The seropositivity rates and antibody concentrations of anti-SARS-CoV-2 NAbs were similar among patients with different severity of CLD 6 months after the third vaccination. In addition, older CLD patients appeared to have lower antibody responses. These data might be helpful to inform vaccine decisions for patients with chronic liver disease.

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.

Chronic liver disease (CLD) patients have higher mortality and hospitalization rates after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to explore SARS-CoV-2 vaccine perceptions, side effects, factors associated with nonvaccination and attitudes toward fourth-dose vaccine among CLD patients. The differences between vaccinated and unvaccinated groups among 1491 CLD patients and the risk factors associated with nonvaccination status were analyzed. In total, 1239 CLD patients were immunized against SARS-CoV-2. CLD patients have a high level of trust in the government and clinicians and were likely to follow their recommendations for vaccination. Reasons reported for nonvaccination were mainly concerns about the vaccines affecting their ongoing treatments and the fear of adverse events. However, only 4.84% of patients reported mild side effects. Risk factors influencing nonvaccination included being older in age, having cirrhosis, receiving treatments, having no knowledge of SARS-CoV-2 vaccine considerations and not receiving doctors' positive advice on vaccination. Furthermore, 20.6% of completely vaccinated participants refused the fourth dose because they were concerned about side effects and believed that the complete vaccine was sufficiently protective. Our study proved that SARS-CoV-2 vaccines were safe for CLD patients. Our findings suggest that governments and health workers should provide more SARS-CoV-2 vaccination information and customize strategies to improve vaccination coverage and enhance vaccine protection among the CLD population.

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.

The present study aimed to evaluate the durability of immune response after basic and booster immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver disease (CLD).

Patients with CLD and complete basic or booster immunization with SARS-CoV-2 vaccines were included in this study. Based on the vaccination situation, they were divided into the basic immunity group (Basic) and the booster immunity group (Booster), which were then subdivided into four groups according to the time interval from completion of basic immunization or booster immunization to serological specimen collection. The positive rates and antibody titers of novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD) were analyzed.

A total of 313 patients with CLD were enrolled in this study, including 201 in Basic and 112 in Booster. The positive rates of nCoV NTAb and nCoV S-RBD within 30 days of completing basic immunization were 80.4% and 84.8%, respectively, but decreased rapidly with the extension of vaccination time, and only 29% and 48.4% of patients with CLD remained positive for nCoV NTAb and nCoV S-RBD, respectively, after 120 days of completing basic immunization. Within 30 days of booster immunization, the positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD rapidly increased from 29.0% and 48.4% at the end of basic immunization to 95.2% and 90.5%, and maintained a high level (defined as the positive rate >50%) until 120 days when the positive rates of nCoV NTAb and nCoV S-RBD were still high at 79.5% and 87.2%, respectively. After basic immunization, the time for nCoV NTAb and nCoV S-RBD to turn negative was 120 and 169 days, respectively, and the negative time of nCoV NTAb and nCoV S-RBD was significantly prolonged to 266 days and 329 days, respectively.

It is safe and effective for patients with CLD to complete basic and booster immunization with SARS-CoV-2 vaccines. After booster immunization, the immune response of patients with CLD was further improved and the durability of the SARS-CoV-2 antibody was significantly prolonged.

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.

The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis.

A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire.

A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001).

Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages.

A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into 'low' or 'high' responders according to IgG levels. Infection rates and severity were collected throughout the study.

Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted 'low' humoral response, whereas viral hepatitis and antiviral therapy predicted 'high' humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy.

Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines.

In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a 'lower' humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a 'higher' humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.

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.

We conducted a matched retrospective cohort study of two cohorts to estimate inactivated vaccine effectiveness (VE) and its comparative effectiveness of booster dose among older people in Shanghai. Cohort 1 consisted of a vaccinated group (≥1 dose) and an unvaccinated group (3,317,475 pairs), and cohort 2 consisted of a booster vaccinated group and a fully vaccinated group (2,084,721 pairs). The Kaplan-Meier method and Cox regression models were used to estimate risk and hazard ratios (HRs) study outcomes. For cohort 1, the overall estimated VEs of ≥1 dose of inactivated vaccine against SARS-CoV-2 infection, severe/critical Covid-19, and Covid-19 related death were 24.7% (95%CI 23.7%-25.7%), 86.6% (83.1%-89.4%), and 93.2% (88.0%-96.1%), respectively. Subset analysis showed that the booster vaccination provided greatest protection. For cohort 2, compared with full vaccination, relative VEs of booster dose against corresponding outcome were 16.3% (14.4%-17.9%), 60.5% (37.8%-74.9%), and 81.7% (17.5%-95.9%). Here we show, although under the scenario of persistent dynamic zero-Covid policy and non-pharmaceutical interventions, promoting high uptake of the full vaccination series and booster dose among older adults is critically important. Timely vaccination with the booster dose provided effective protection against Covid-19 outcomes.

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.

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.

Bacterial and viral infections are common in cirrhotic patients, and their occurrence is associated with the severity of liver disease. Bacterial infection may increase the probability of death by 3.75 times in patients with decompensated cirrhosis, with ranges of 30% at 1 month and 63% at 1 year after infection. We illustrate the indications and the modalities for vaccinating cirrhotic patients. This topic is important for general practitioners and specialists.

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.