Canha Inês, Silva Mário Jorge, Silva Maria Azevedo, Sarmento Costa Mara, Saraiva Rita Ornelas, Ruge André, Machado Mariana Verdelho, Félix Catarina Sousa, Morão Bárbara, Figueiredo Pedro Narra, Mendes Milena, Leal Carina, Calinas Filipe
Gastroenterology Department, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.
NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.
GE Port J Gastroenterol. 2023 Nov 15;31(5):325-337. doi: 10.1159/000534740. eCollection 2024 Oct.
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 ( = 59, 48%), ChAdOx1nCoV-19 ( = 45, 36%), mRNA-1273 ( = 14, 11%), and Ad26.COV2.S ( = 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 ( < 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.
在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行开始三年后，新型冠状病毒肺炎（COVID-19）疫苗在肝硬化（LC）患者中的安全性和有效性仍存在争议。我们旨在研究LC患者对COVID-19疫苗接种的安全性、免疫反应和临床反应。
对符合COVID-19疫苗接种条件、既往无已知感染的成年LC患者进行前瞻性多中心研究。对患者进行随访，直至接种加强针、感染SARS-CoV-2或死亡。评估接种疫苗后2周、3个月和6个月时SARS-CoV-2的刺突蛋白免疫球蛋白G抗体滴度。抗体滴度<33.8结合抗体单位（BAU）/mL被视为血清阴性，<200 BAU/mL为次优。记录接种疫苗后的感染情况及其严重程度。
我们纳入了124例LC患者，其中81%为男性，平均年龄61±10岁，平均随访221±26天。酒精是最常见的（61%）肝硬化病因，7%的患者因自身免疫性肝炎接受免疫抑制剂治疗；69%的患者有门静脉高压，42%的患者曾有失代偿，21%的患者Child-Pugh-Turcotte评分B/C级。接种的疫苗类型为BNT162b2（n = 59，48%）、ChAdOx1 nCoV-19（n = 45，36%）、mRNA-1273（n = 14，11%）和Ad26.COV2.S（n = 6，5%）。18%的患者报告接种疫苗后出现不良事件，均不严重。接种后2周、3个月和6个月时抗体滴度的中位数[四分位数间距1；四分位数间距3]分别为118[280；2080]BAU/mL、301[72；1175]BAU/mL和192[49；656]BAU/mL。接种后2周、3个月和6个月时，分别有8%和23%、16%和38%、22%和48%的患者出现血清阴性和次优抗体反应。在多变量逻辑回归分析中，年龄较大和腺病毒载体疫苗是接种后2周和3个月时与血清阴性和次优反应相关的唯一因素（P<0.05）。11例（9%）患者在随访期间（接种疫苗后3.8 - 6.6个月）感染SARS-CoV-2，均为轻症。疫苗类型之间无差异，73%的患者在3个月时抗体滴度>200 BAU/mL。
LC患者接种COVID-19疫苗是安全的，无严重不良事件。体液和临床反应与普通人群报道的相似。体液反应受到年龄较大和腺病毒载体疫苗的不利影响，与肝脏疾病严重程度无关。
