Yan Kathleen, Garcia-Tsao Guadalupe
a Digestive Diseases Section , Yale University School of Medicine , New Haven , CT , USA.
b Digestive Diseases Section , VA-CT Healthcare System , West Haven , CT , USA.
Expert Opin Pharmacother. 2016;17(5):689-701. doi: 10.1517/14656566.2016.1145663. Epub 2016 Feb 23.
Bacterial infections are a serious complication of cirrhosis, as they can lead to decompensation, multiple organ failure, and/or death. Preventing infections is therefore very relevant. Because gut bacterial translocation is their main pathogenic mechanism, prevention of infections is mostly based on the use of orally administered poorly absorbed antibiotics such as norfloxacin (selective intestinal decontamination). However, antibiotic prophylaxis leads to antibiotic resistance, limiting therapy and increasing morbidity and mortality. Prevention of bacterial infections in cirrhosis should therefore move away from antibiotics.
This review focuses on various potentially novel methods to prevent infections in cirrhosis focusing on non-antibiotic strategies. The use of probiotics, nonselective intestinal decontamination with rifaximin, prokinetics and beta-blockers or fecal microbiota transplant as means of targeting altered gut microbiota, bile acids and FXR agonists are all potential alternatives to selective intestinal decontamination. Prokinetics and beta-blockers can improve intestinal motility, while bile acids and FXR agonists help by improving the intestinal barrier. Finally, granulocyte colony stimulating factor (G-CSF) and statins are emerging therapeutic strategies that may improve immune dysfunction in cirrhosis.
Evidence for these strategies has been restricted to animal studies and proof-of concept studies but we expect this to change in coming years.
细菌感染是肝硬化的严重并发症，因为它们可导致失代偿、多器官功能衰竭和/或死亡。因此，预防感染非常重要。由于肠道细菌易位是其主要致病机制，感染的预防主要基于使用口服吸收不良的抗生素，如诺氟沙星（选择性肠道去污）。然而，抗生素预防会导致抗生素耐药性，限制治疗并增加发病率和死亡率。因此，肝硬化细菌感染的预防应摒弃抗生素。
本综述重点关注预防肝硬化感染的各种潜在新方法，侧重于非抗生素策略。使用益生菌、利福昔明进行非选择性肠道去污、促动力药和β受体阻滞剂或粪便微生物群移植作为针对肠道微生物群改变的手段，胆汁酸和法尼醇X受体（FXR）激动剂都是选择性肠道去污的潜在替代方法。促动力药和β受体阻滞剂可改善肠道蠕动，而胆汁酸和FXR激动剂通过改善肠道屏障发挥作用。最后，粒细胞集落刺激因子（G-CSF）和他汀类药物是新兴的治疗策略，可能改善肝硬化中的免疫功能障碍。
这些策略的证据仅限于动物研究和概念验证研究，但我们预计未来几年情况会有所改变。
