hepatitis A virus

甲型肝炎病毒
  • 文章类型: Journal Article
    我们评估了在6-15个月开始接种疫苗后23年与甲型肝炎病毒抗体存在相关的因素。在67名参与者中,86%(42/49)在12-15个月接种疫苗的人和61%(11/18)在6个月接种疫苗的人在23岁时保持血清阳性。招募时缺乏母体抗体和较高的初始疫苗应答与23岁时较高的抗体浓度独立相关。需要进一步的研究来评估甲型肝炎疫苗保护的持续时间以及可能需要加强剂量。
    We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose.
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  • 文章类型: Journal Article
    轮状病毒和甲型肝炎病毒是引起胃肠炎和黄疸的原因。目前的疫苗接种方法已被证明是不够的,特别是在低收入国家。在这项研究中,我们提出了一种新的联合轮状病毒VP8蛋白和甲型肝炎病毒VP1的双重候选疫苗.
    使用大肠杆菌表达系统产生VP8*-轮状病毒+AAY+HAV-VP1融合蛋白。重组蛋白的分子量约为45.5kDa,通过亲和层析纯化。BALB/c小鼠皮下注射重组蛋白,VP1,VP8和轮状病毒和甲型肝炎病毒疫苗,有和没有ALUM和M720佐剂。ELISA测定用于测量总IgG,IgG1、IgG2以及短期和长期IL-5和IFN-γ应答。
    融合蛋白,当与佐剂结合使用时,引起明显更高的总IgG,与单独的VP1和VP8相比,IgG1和IgG2应答,以及轮状病毒和甲型肝炎疫苗。此外,与轮状病毒和甲型肝炎疫苗相比,它诱导了更高的短期IL-5和IFN-γ反应,同时表现出更高的长期IL-5反应。
    这项研究表明,VP8*-轮状病毒+AAY+HAV-VP1融合蛋白是免疫甲型肝炎和轮状病毒的有希望的双重疫苗候选物。
    UNASSIGNED: Rotavirus and Hepatitis A virus are responsible for causing gastroenteritis and jaundice. The current vaccination approaches have proven insufficient, especially in low-income countries. In this study, we presented a novel dual-vaccine candidate that combines the rotavirus VP8 protein and the hepatitis A virus VP1.
    UNASSIGNED: The VP8*-rotavirus+AAY+HAV-VP1 fusion protein was produced using an Escherichia coli expression system. The recombinant protein had a molecular weight of approximately 45.5 kDa and was purified through affinity chromatography. BALB/c mice were injected subcutaneously with the recombinant protein, VP1, VP8 and vaccines for rotavirus and hepatitis A virus, both with and without ALUM and M720 adjuvants. ELISA assays were used to measure total IgG, IgG1, IgG2, and short-term and long-term IL-5 and IFN-γ responses.
    UNASSIGNED: The fusion protein, when combined with adjuvants, elicited significantly higher total IgG, IgG1, and IgG2 responses compared to VP1 and VP8 alone, as well as the rotavirus and hepatitis A vaccines. Furthermore, it induced a higher short-term IL-5 and IFN-γ response while demonstrating a higher long-term IL-5 response compared to the rotavirus and hepatitis A vaccines.
    UNASSIGNED: This study demonstrates that the VP8*-rotavirus+AAY+HAV-VP1 fusion protein is a promising dual vaccine candidate for immunization against hepatitis A and rotaviruses.
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  • 文章类型: Journal Article
    背景:甲型肝炎病毒(HAV)是世界范围内急性病毒性肝炎的主要原因;然而,关于移民人群中HAV抗体患病率(血清阳性率)的数据有限.本研究旨在调查卡塔尔移民手工工人和体力劳动者(CMW)的HAV血清阳性率,约占全国人口的60%。
    方法:在2020年7月26日至9月9日进行的全国性严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)人群横断面调查中,对从CMW获得的储存血清标本进行了HAV抗体检测。通过回归分析研究与HAV感染的关联。
    结果:在具有HAV抗体检测结果的2,607个样本中,2,393为阳性,214是阴性。估计CMW中的HAV血清阳性率为92.0%(95%CI:90.9-93.1%)。HAV血清阳性率普遍较高,但表现出一些变异,范围从70.9%(95%CI:62.4-78.2%)在斯里兰卡和99.8%(95%CI:98.2-99.9%)在巴基斯坦。多元回归分析确定了年龄,国籍,和教育程度是与HAV感染相关的统计学显著因素。相对于年龄≤29岁的CMW,30~39岁CMW的校正相对危险度(ARR)为1.06(95%CI:1.03~1.10),≥50岁CMW的校正相对危险度(ARR)为1.15(95%CI:1.10~1.19).与印度人相比,斯里兰卡的ARR较低,评估为0.81(95%CI:0.72-0.91),但尼泊尔人较高,为1.07(95%CI:1.04-1.11),孟加拉国为1.10(95%CI:1.07-1.13),巴基斯坦人在1.12(95%CI:1.09-1.15),和埃及人在1.15(95%CI:1.08-1.23)。没有发现因地理位置或职业而异的证据。
    结论:卡塔尔CMW人群中的HAV血清阳性率非常高,每10个人中就有9个人暴露于这种感染,可能在童年。
    BACKGROUND: Hepatitis A virus (HAV) is the predominant cause of acute viral hepatitis worldwide; however, data on HAV antibody prevalence (seroprevalence) among migrant populations are limited. This study aimed to investigate HAV seroprevalence among Qatar\'s migrant craft and manual workers (CMWs), constituting approximately 60% of the country\'s population.
    METHODS: HAV antibody testing was conducted on stored serum specimens obtained from CMWs during a nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) population-based cross-sectional survey between July 26 and September 9, 2020. Associations with HAV infection were investigated through regression analyses.
    RESULTS: Of the 2,607 specimens with HAV antibody test results, 2,393 were positive, and 214 were negative. The estimated HAV seroprevalence among CMWs was 92.0% (95% CI: 90.9-93.1%). HAV seroprevalence was generally high but exhibited some variation, ranging from 70.9% (95% CI: 62.4-78.2%) among Sri Lankans to 99.8% (95% CI: 98.2-99.9%) among Pakistanis. The multivariable regression analysis identified age, nationality, and educational attainment as statistically significant factors associated with HAV infection. Relative to CMWs aged ≤29 years, the adjusted relative risk (ARR) was 1.06 (95% CI: 1.03-1.10) in CMWs aged 30-39 years and reached 1.15 (95% CI: 1.10-1.19) in those aged ≥50 years. In comparison to Indians, the ARR was lower among Sri Lankans, assessed at 0.81 (95% CI: 0.72-0.91), but higher among Nepalese at 1.07 (95% CI: 1.04-1.11), Bangladeshis at 1.10 (95% CI: 1.07-1.13), Pakistanis at 1.12 (95% CI: 1.09-1.15), and Egyptians at 1.15 (95% CI: 1.08-1.23). No evidence for differences was found by geographic location or occupation.
    CONCLUSIONS: HAV seroprevalence among Qatar\'s CMW population is very high, with over nine out of every ten individuals having been exposed to this infection, likely during childhood.
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  • 文章类型: Case Reports
    背景:急性甲型肝炎感染在发展中国家的儿童中很常见。儿童的临床表现通常是无症状和黄疸,这是一种自限性感染。很少,它可能与胸腔积液等肝外并发症有关,无结石性胆囊炎,和腹水。
    方法:一名8岁的中东儿童出现腹痛,巩膜黄疸,尿液的黄色,食欲不振。在过去的两天里,腹胀。在进行诊断调查后,患儿被诊断为伴有双侧胸腔积液的HAV肝炎,无结石性胆囊炎,和腹水。他接受了补充维生素K和支持性肠胃外液体的保守治疗。4天后,观察到临床改善。
    结论:甲型肝炎感染表现为肝外表现,如胸腔积液,无结石性胆囊炎,腹水非常罕见,尤其是儿童。有一些报道称这些表现是孤立发生的,但是为了让他们根据我们的知识共存,这只在文献中报道了两个案例,这是第三种情况,所有这三种罕见的并发症同时出现在一个孩子身上。尽管HAV感染在儿童时期是一种无症状和自限性的病毒性疾病,它可以表现为罕见的肝外并发症,所以儿科医生应该意识到这种罕见的关联,以避免不必要的调查。
    BACKGROUND: Acute hepatitis A infection is common among children in developing nations. The clinical presentation in children is usually asymptomatic and anicteric, and it is a self-limiting infection. Rarely, it can be associated with extrahepatic complications such as pleural effusion, acalculous cholecystitis, and ascites.
    METHODS: An 8-year-old middle eastern child presented with abdominal pain, jaundice in the sclera, yellowish color of urine, and poor appetite. In the last two days, abdominal distension developed. After conducting diagnostic investigations, the child was diagnosed with HAV hepatitis associated with bilateral pleural effusion, acalculous cholecystitis, and ascites. He was managed conservatively with vitamin K supplementation and supportive parenteral fluids. After 4 days, clinical improvement was observed.
    CONCLUSIONS: Hepatitis A infections presented with extrahepatic manifestations like pleural effusion, acalculous cholecystitis, and ascites are very rare, especially in children. There have been some reports of these manifestations occurring in isolation, but for them to co-exist to our knowledge, this has only been reported in two cases in the literature, and this is the third case with all these three rare complications being presented simultaneously in a single child. Although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications, so pediatricians should be aware of this rare association to avoid unnecessary investigations.
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  • 文章类型: Case Reports
    中毒性表皮坏死松解症(TEN)是一种罕见但严重的免疫介导的危及生命的皮肤和粘膜反应,主要由药物引起,感染,疫苗,和恶性肿瘤。一名74岁的妇女出现不明原因的中度发烧,两天后缓解了,但是虚弱和食欲下降。颈部先后出现红色斑丘疹,树干,和四肢,逐渐扩大,形成疱疹和融合,含有黄色浑浊的液体,并破裂,露出明亮的红色侵蚀表面,散布在眼睛和嘴巴周围。受影响的身体表面积>90%。中毒性表皮坏死松解症的病情严重程度评分为2分。药疹面积和严重度指数评分为77。她被诊断为甲型肝炎病毒引起的TEN,并接受了160毫克/天的甲基强的松龙治疗,300毫克/天环孢菌素,和20克/天丙种球蛋白。治疗3天后,她的皮肤改善,1个月后恢复到接近正常,2个月后肝功能完全正常。
    Toxic epidermal necrolysis (TEN) is a rare but serious immune-mediated life-threatening skin and mucous membrane reaction that is mainly caused by drugs, infections, vaccines, and malignant tumors. A 74-year-old woman presented with a moderate fever of unknown cause, which was relieved after 2 days, but with weakness and decreased appetite. Red maculopapules appeared successively on the neck, trunk, and limbs, expanding gradually, forming herpes and fusion, containing a yellow turbidous liquid and rupturing to reveal a bright red erosive surface spreading around the eyes and mouth. The affected body surface area was >90%. The severity of illness score for toxic epidermal necrolysis was 2 points. The drug eruption area and severity index score was 77. She was diagnosed with TEN caused by hepatitis A virus and treated with 160 mg/day methylprednisolone, 300 mg/day cyclosporine, and 20 g/day gammaglobulin. Her skin showed improvements after 3 days of treatment and returned to nearly normal after 1 month, and liver function was completely normal after 2 months.
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  • 文章类型: Journal Article
    食源性传播是许多与胃肠道相关的病毒的公认途径,肝,或神经系统疾病。因此,它是必不可少的,以确定新的生物活性的广谱抗抗病毒活性的化合物,利用创新的解决方案来应对这些危害。最近,抗微生物肽(AMP)已被认为是有前途的抗病毒剂。的确,虽然这些分子的抗菌和抗真菌作用已被广泛报道,它们作为潜在抗病毒药物的用途尚未得到充分研究。在这里,先前鉴定或新设计的AMP的抗病毒活性被评估为对抗无包膜RNA病毒,甲型肝炎病毒(HAV)和鼠诺如病毒(MNV),人类诺如病毒的替代品.此外,进行特异性测定以识别肽可以在病毒感染周期的哪个阶段发挥作用。结果表明,几乎所有的肽都表现出杀病毒作用,在HAV或MNV中具有约90%的感染性降低。然而,证明了十肽RiLK1,连同其抗菌和抗真菌特性,HAV和MNV的病毒感染显着减少,可能是通过与病毒颗粒的直接相互作用导致其损伤或阻碍细胞受体的识别。因此,RiLK1可以代表一种通用的抗微生物剂,可有效对抗各种食源性病原体,包括病毒,细菌,和真菌。
    Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic, or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity to exploit innovative solutions against these hazards. Recently, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs was evaluated against the non-enveloped RNA viruses, hepatitis A virus (HAV) and murine norovirus (MNV), a surrogate for human norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. The results showed that almost all peptides displayed virucidal effects, with about 90% of infectivity reduction in HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles causing their damage or hindering the recognition of cellular receptors. Hence, RiLK1 could represent a versatile antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.
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  • 文章类型: Journal Article
    病毒性肝炎对公众健康构成重大威胁,是全球主要的死亡原因。五种肝脏特异性病毒:甲型肝炎病毒,乙型肝炎病毒,丙型肝炎病毒,丁型肝炎病毒,和戊型肝炎病毒,每个人都有自己独特的流行病学,结构生物学,传输,地方性模式,肝脏并发症的风险,以及对抗病毒治疗的反应。治疗的选择仍然很少,尽管病毒性肝炎引起的肝病患病率不断上升。此外,慢性病毒性肝炎是肝脏相关发病率和死亡率的全球主要原因,即使有效的治疗方法可以减少或预防大多数患者的并发症。2016年,世界卫生组织发布了到2030年消除病毒性肝炎作为公共卫生威胁的计划,并讨论了区域和全球根除病毒性肝炎的当前差距和前景。今天,治疗足以防止疾病达到晚期。然而,未来的疗法必须非常安全,并且应该理想地限制必要的治疗时间。对发病机理的更好理解将证明有益于开发针对病毒性肝炎感染的潜在治疗策略。这篇综述旨在总结每种类型的病毒性肝炎的知识现状,以及重大创新。
    Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients\' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.
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  • 文章类型: Journal Article
    准确的检测,identification,随后确认导致食源性疾病的病原体对于预防和调查食源性疾病至关重要。当病原体是具有非常低的感染剂量并且可能以检测极限或接近检测极限存在的肠道病毒时,尤其如此。在这项研究中,将全基因组测序(WGS)与两种非靶向预扩增方法(SPIA和SISPA)中的任一种相结合,以研究它们作为被肠道病毒污染的食品的RT-qPCR阳性结果的验证性方法的实用性.冷冻浆果(覆盆子,草莓,和黑莓)被选为感兴趣的食物基质,因为它们与许多食源性疾病的爆发有关。使用甲型肝炎病毒(HAV)和人诺如病毒(HuNoV)作为污染剂。本研究中采用的非靶向WGS策略可以检测并确认基因组拷贝数在个位数范围内的HuNoV和HAV。在一些情况下,通过RT-qPCR分析发现样品中存在的病毒呈阴性。然而,一些RT-qPCR阳性样本无法使用WGS方法确认,在Ct值很高的情况下,从样品中只回收了一些病毒读段和短序列。WGS技术在确认和鉴定受病毒污染的食品方面显示出巨大的潜力。这里描述的方法应进一步优化以用于常规应用,以确认浆果中的病毒污染。
    Accurate detection, identification, and subsequent confirmation of pathogens causing foodborne illness are essential for the prevention and investigation of foodborne outbreaks. This is particularly true when the causative agent is an enteric virus that has a very low infectious dose and is likely to be present at or near the limit of detection. In this study, whole-genome sequencing (WGS) was combined with either of two non-targeted pre-amplification methods (SPIA and SISPA) to investigate their utility as a confirmatory method for RT-qPCR positive results of foods contaminated with enteric viruses. Frozen berries (raspberries, strawberries, and blackberries) were chosen as the food matrix of interest due to their association with numerous outbreaks of foodborne illness. The hepatitis A virus (HAV) and human norovirus (HuNoV) were used as the contaminating agents. The non-targeted WGS strategy employed in this study could detect and confirm HuNoV and HAV at genomic copy numbers in the single digit range, and in a few cases, identified viruses present in samples that had been found negative by RT-qPCR analyses. However, some RT-qPCR-positive samples could not be confirmed using the WGS method, and in cases with very high Ct values, only a few viral reads and short sequences were recovered from the samples. WGS techniques show great potential for confirmation and identification of virally contaminated food items. The approaches described here should be further optimized for routine application to confirm the viral contamination in berries.
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  • 文章类型: Case Reports
    背景:急性非结石性胆囊炎(AAC)定义为无结石的胆囊炎。相反,甲型肝炎病毒(HAV)可以表现出不同的症状;然而,HAV引起和呈现为AAC是罕见的。
    方法:41岁以前健康的患者出现右上腹腹痛。疼痛持续并伴有呕吐,实验室检查显示胆红素升高。腹腔镜胆囊切除术显示胆囊发炎,无结石,术中胆管造影未见异常。手术后的第一天,当疼痛缓解时,实验室显示肝功能测试升高,肝炎检查显示急性HAV感染,将她的表现归因于HAV诱导的AAC。
    结论:AAC通常是由不同原因引起的胆囊淤滞引起的;然而,HAV诱导的AAC很少有报道。虽然胆囊切除术是AAC的主要治疗方法,HAV诱导的AAC可能不是这种情况。例如,除非胆囊坏死或症状持续存在,在这种情况下,可以保守地管理AAC。即使我们的诊断在手术后被清除,如果我们以前知道HAV诱导的AAC的诊断,由于疼痛的严重程度和持续性,我们仍然会选择手术。
    结论:应报告更多病例,并进行更多研究以进一步确定HAV诱导的AAC的表现和管理。
    BACKGROUND: acute acalculous cholecystitis (AAC) is defined as gallbladder inflammation without the presence of stones. Contrary, hepatitis A virus (HAV) can present with different symptoms; however, HAV causing and presenting as AAC is rare.
    METHODS: 41-year-old previously healthy patient presented with right upper quadrant abdominal pain. The pain was persistent and associated with vomiting and laboratory tests showed elevated bilirubin. Laparoscopic cholecystectomy showed inflamed gallbladder with no stones and intraoperative cholangiography showed no abnormalities. Day one post-operation, while the pain resolved, labs showed elevated liver function tests and hepatitis workup showed acute HAV infection attributing her presentation to HAV induced AAC.
    CONCLUSIONS: AAC is usually caused by stasis of the gallbladder due to different causes; however, HAV induced AAC has been rarely reported. While cholecystectomy is the mainstay treatment for AAC, this might not be the case for HAV induced AAC. For instance, unless there is necrotic gallbladder or persistence of symptoms, AAC can be managed conservatively in this case. Even though our diagnosis was cleared post-operatively, had we knew the diagnosis of HAV induced AAC before, we would have still opt for surgery due to the severity and persistence of pain.
    CONCLUSIONS: More cases should be reported and more studies should be done to further define the presentation and management of HAV induced AAC.
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  • 文章类型: Journal Article
    疫苗每年预防大量死亡。然而,由于免疫系统受损,某些人群对疫苗接种没有足够的反应。肝硬化,一种以免疫力严重受损为标志的疾病,损害了正常的免疫接种过程。肝硬化患者的关键疫苗,例如甲型肝炎病毒(HAV),乙型肝炎病毒(HBV),流感,肺炎球菌,和冠状病毒病19(COVID-19),经常引起这些个体的次优反应。体液反应,对免疫至关重要,由于B记忆细胞的减少和血浆母细胞的增加,在肝硬化中效果较差,这干扰了对抗原疫苗接种的持久反应的产生。此外,一些T细胞亚型在肝硬化中显示出降低的活化。尽管如此,记忆T细胞活性的持久性,虽然不能预防感染,可能有助于减轻这些患者疾病的严重程度。除此之外,先天免疫的损害,特别是在树突状细胞(DC)中,防止适应性免疫的正常启动,在免疫过程开始时中断。此外,肝硬化破坏了肠-肝轴平衡,导致生态失调,减少短链脂肪酸(SCFA)的产生,肠道通透性增加,和细菌移位。破坏免疫系统的生理活动,这些改变可能会影响疫苗的反应.增强对导致肝硬化患者疫苗接种反应受损的分子和细胞因子的理解对于提高该人群的疫苗效力和制定更好的预防策略至关重要。
    Vaccines prevent a significant number of deaths annually. However, certain populations do not respond adequately to vaccination due to impaired immune systems. Cirrhosis, a condition marked by a profound disruption of immunity, impairs the normal immunization process. Critical vaccines for cirrhotic patients, such as the hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcal, and coronavirus disease 19 (COVID-19), often elicit suboptimal responses in these individuals. The humoral response, essential for immunization, is less effective in cirrhosis due to a decline in B memory cells and an increase in plasma blasts, which interfere with the creation of a long-lasting response to antigen vaccination. Additionally, some T cell subtypes exhibit reduced activation in cirrhosis. Nonetheless, the persistence of memory T cell activity, while not preventing infections, may help to attenuate the severity of diseases in these patients. Alongside that, the impairment of innate immunity, particularly in dendritic cells (DCs), prevents the normal priming of adaptive immunity, interrupting the immunization process at its onset. Furthermore, cirrhosis disrupts the gut-liver axis balance, causing dysbiosis, reduced production of short-chain fatty acids (SCFAs), increased intestinal permeability, and bacterial translocation. Undermining the physiological activity of the immune system, these alterations could impact the vaccine response. Enhancing the understanding of the molecular and cellular factors contributing to impaired vaccination responses in cirrhotic patients is crucial for improving vaccine efficacy in this population and developing better prevention strategies.
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