Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level

Recurrent and treatment-unresponsive spontaneous bacterial peritonitis worsens survival in decompensated liver cirrhosis

Background: Spontaneous bacterial peritonitis (SBP) remains a major complication of cirrhosis. However, the incidence and the real impact of SBP in determining patient survival rates remain unclear. This study aims to evaluate the incidence and risk factors for SBP development and the role of SBP in predicting transplant-free survival. Methods: Two hundred two consecutive patients underwent 492 paracenteses with biochemical and microbiological analysis of the ascitic fluid. When multiple paracenteses had been performed on a given patient, the first SBP-positive paracentesis or the first paracentesis conducted when none was diagnostic for SBP was included in the study. Results: SBP was detected in 28 of 202 (13.9%) patients; in 26 of 28 patients, the neutrophil count in the ascitic fluid was $250 cells/ml, and in 15 of 28 patients, the cultures were positive. Variables inde- pendently associated with SBP were as follows: a higher model of end-stage liver disease (MELD) score, the serum glucose value, elevated CRP serum levels, and higher potassium serum levels. Overall, the median (range) transplant-free survival was 289 (54\u20131253) days. One hundred (49.5%) patients died, whereas 35 patients (17.3%) underwent liver transplantation. Independent predictors of death or liver transplantation were a higher MELD score and the development of SBP, especially if it was antibiotic-resistant or recurrent SBP. Conclusion: The occurrence of SBP is associated with more severe liver dysfunction in conjunction with the presence of inflammation. Unlike the occurrence of SBP per se, failure of first-line antibiotic treatment and SBP recurrence appear to strongly influence the mortality rat

Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C.

Host genetic variation may affect the outcome of chronic viral hepatitides, favoring viral clearance and/or modulating the inflammatory response to persistent infection. Our aims were to assess whether interleukin 6 (IL-6) promoter polymorphisms are associated with chronic hepatitis C virus (HCV) infection and to clarify the role of IL-6 haplotypes in facilitating progressive disease. The study included 424 Italian patients (233 males, median age 53 years) affected by HCV chronic infection. IL6 -1363, -597, -572, -174, and +2954 polymorphic loci were assayed by means of restriction fragment length polymorphism. Three hundred forty-four healthy Italian blood donors (245 males, median age 50 years) served as controls. Comparing patients and controls analysis of molecular variance was highly significant (p\u2009<\u20090.0001); at a locus by locus approach, the frequencies of minor alleles in the -1363 (p\u2009<\u20090.02), -597 (p\u2009<\u20090.02), and -174 (p\u2009<\u20090.01) polymorphisms were confirmed to be less represented in patients than in controls. Carrying the wild-type G allele at the -597 and -174 loci identified an unfavorable haplotype; carrying the minor allele in one/both loci identified an indifferent/favorable haplotype. Male patients carrying two unfavorable haplotypes had the highest adjusted mean\u2009\ub1\u2009standard error Ishak staging score (3.56\u2009\ub1\u20090.19), while females carrying one or no unfavorable haplotypes had the lowest (2.69\u2009\ub1\u20090.21); the remaining patients had an intermediate value (3.12\u2009\ub1\u20090.13, p\u2009<\u20090.01). In conclusion, IL-6 promoter polymorphisms influence the development of chronic HCV infection. With the permissive effect of male gender, haplotypes represented by the wild-type allele for -597 and -174 loci appear to favor a worse evolution of the disease

Biliary strictures after liver transplantation: Role of interleukin 28B genotypes in cyclosporine treated

AbstractIntroduction: The role of Interleukin 28B (IL-28B) genetic polymorphisms in influencing the occurrence of biliary complications after liver transplantation has never been evaluated. This study aimed to investigate whether IL-28B rs12979860C/T polymorphisms associate with the occurrence of biliary complications after liver transplantation and if these complications may influence survival. Methods: One hundred seventy one recipients (133 males) who underwent liver transplantation were recruited. To confirm the mechanical etiology of cholestasis, endoscopic cholangio pancreatography, percutaneous and/or trans-Kehr cholangiography or cholangio magnetic resonance were performed. Two main clinical pictures were identified: biliary strictures and biliary leakage. Immunosuppressive therapy was based on cyclosporine (N = 54) or tacrolimus (N = 117), in association with steroids during the first month after operation. IL-28B rs12979860C/T genotypes were detected by means of polymerase chain reaction. Results: Forty patients (23.4%) presented anastomotic strictures, 7 (4.1%) non-anastomotic strictures, 10 (5.8%) leakage, 8 (4.7%) leakage plus anastomotic strictures. IL-28B rs12979860C/C genotype in association with cyclosporin was found to be an independent predictor of anastomotic strictures occurrence (p = 0.008). A significant difference in 5 years survival was observed between patients with viral etiology of liver disease experiencing either anastomotic or non-anastomotic strictures (16/23) and the remaining patients (104/112, p = 0.001). Conclusions: In recipients carrying rs12979860 IL-28B C/C genotype the use of cyclosporine seems to contribute to enhance the probability of developing biliary complications which in hepatitis B and C positives appear to reduce patient survival. If confirmed in larger studies the use of cyclosporine in these patients could be revised

Morbidity and mortality after transjugular intrahepatic portosystemic shunt placement in patients with cirrhosis

Transjugular intrahepatic portosystemic shunt (TIPS) is adopted to treat refractory complications of portal hypertension, such as variceal bleeding and ascites. This study aimed to assess predictors of hepatic encephalopathy (HE) development and cumulative transplant-free survival after TIPS placement in patients with cirrhosis complicated by refractory ascites and major gastroesophageal bleeding

Low risk of nosocomial severe acute respiratory syndrome-coronavirus-2 infection in patients with liver disease admitted to a hepatology unit at an academic hospital: A single-center experience

Background: Patients with liver disease may be at increased risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection due to immune dysfunction. However, the risk of nosocomial SARS-CoV-2 infection in these patients remains unknown. This study aimed to determine whether patients with liver disease are at an increased risk of nosocomial transmission of SARS-CoV-2 infection upon admission to the hospital for diagnostic or therapeutic procedures. Methods: The study prospectively enrolled 143 patients who were admitted at least once to the hepatology unit at our hospital; 95 patients (66%) were admitted at least twice during the study period. History of past symptomatic SARS-CoV-2 exposure was assessed on the day before hospital admission via an interview. Patients were evaluated for active SARS-CoV-2 infection via real-time reverse transcription–polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs and tests for serum anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Results: None of the patients enrolled tested positive for SARS-CoV-2 infection by RT-PCR at the first or the second clinical evaluation. One patient who had previously received a liver transplant and who had a history of symptomatic SARS-CoV-2 infection that occurred 4 months before hospital admission tested positive for anti-SARS-CoV-2 IgG but not IgM antibodies at each of the two hospital admissions. Conclusions: The results of our study suggest that patients with liver disease are at no increased risk of nosocomial SARS-CoV-2 infection. These data support the policy of maintaining clinical hospital checks that will be necessary until or possibly even after the completion of the current SARS-CoV-2 vaccination campaign

The interleukin 28B rs12979860 C/T polymorphism and serum cholesterol as predictors of fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases

The interleukin 28B (IL-28B) rs12979860 C/T polymorphism is a predictor of spontaneous and treatment-induced hepatitis C virus (HCV) clearance. The C/C genotype is associated with higher serum cholesterol, predictor of a favorable outcome in chronic hepatitis C. Whether IL-28B polymorphism and serum cholesterol play a role in modulating the history of mild hepatitis C is unknown. To clarify this issue, 93 untreated patients infected with HCV with normal or near-normal transaminases and an initial Ishak staging score ≤1 were investigated retrospectively in the longitudinal study (median histological follow-up of 10 years). An additional confirmatory cohort of 143 patients with chronic HCV infection and abnormal levels of transaminases was evaluated in the cross-sectional study. In the longitudinal study, at the end of follow-up, Ishak staging scores progressed more frequently among carriers of a T/* allele who had a baseline serum cholesterol ≤175 mg/dl than in remaining patients: 6/36 (change ≤0), 15/45 (change 1-2), 6/12 (change ≥3), improvement chi-square P < 0.02, OR 3.1, 95% C.I. 1.3-7.7. In the cross-sectional study, the frequency of patients carrying the T/T genotype or serum cholesterol values ≤175 mg/dl increased starting from those with a staging score ≤2 (36/76, 47.4%), to those with a staging score of 3-4 (26/41, 63.4%) and to those with a staging score of 5-6 (20/26, 76.9%, P < 0.01 for linear trend). In conclusion, the interaction between IL-28B rs12979860 T/T genotype and low serum cholesterol concentration is an independent predictor of a worse disease course among patients infected with HCV with normal or near-normal transaminases

Recipient Interleukin-28B Rs12979860 C/T Polymorphism and Acute Cellular Rejection After Liver Transplantation: Role of the Calcineurin Inhibitor Used

Background. Interleukin-28 (IL-28B) rs12979860 C/T polymorphism is known to predict the outcome of antiviral therapy in hepatitis C. In addition to its interferon-like and antiviral functions, IL-28B possesses the ability to modulate CD8(+) T cells function. This study aimed to investigate whether recipient IL-28B polymorphism may have a role in predicting the occurrence of acute cellular rejection (ACR) after liver transplantation (LT). Methods. Two hundred fifty-one consecutive LT recipients were enrolled. All the patients underwent per protocol liver biopsies at 1, 3, and 12 months after LT. ACR episodes in the first post-LT year were recorded and graded according to the Banff score. Results. At least one moderate to severe (Banff score >= 5) ACR episode was reported in 75 patients (29.9%). ACR was associated with IL-28B polymorphism: C/C=21/102 (20.6%), C/T=43/126 (34.1%), and T/T=11/23 (47.8%) (P=0.003). At logistic regression analysis, IL-28B polymorphism was found to be a predictor of ACR (P=0.012) together with cytomegalovirus reactivation (P=0.023). The association between IL-28B polymorphism and ACR occurrence was evident in tacrolimus but not in cyclosporine-treated patients. ACR episodes occurred more frequently from hepatitis C virus (HCV) negatives carrying the IL-28B C/C genotype (17.8%) to HCV negatives carrying at least one T allele or HCV positives carrying at least one C allele (33.3%) to HCV positives carrying the T/T genotype (50.0%, P=0.002). Conclusions. HCV etiology in association with the carriage of IL-28B T/T genotype predicted the highest frequency of ACR. Recipient's IL-28B genotyping could be a useful tool in individualizing immunosuppressive therapy according to the risk of ACR occurrence