Bajaj Jasmohan S, Fagan Andrew, Sikaroodi Masoumeh, White Melanie B, Sterling Richard K, Gilles HoChong, Heuman Douglas, Stravitz Richard T, Matherly Scott C, Siddiqui Mohammed S, Puri Puneet, Sanyal Arun J, Luketic Velimir, John Binu, Fuchs Michael, Ahluwalia Vishwadeep, Gillevet Patrick M
Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia.
Microbiome Analysis Center, George Mason University, Manassas, Virginia.
Liver Transpl. 2017 Jul;23(7):907-914. doi: 10.1002/lt.24754.
Liver transplantation (LT) improves daily function and cognition in patients with cirrhosis, but a subset of patients can remain impaired. Unfavorable microbiota or dysbiosis is observed in patients with cirrhosis, but the effect of LT on microbial composition, especially with poor post-LT cognition, is unclear. The aims were to determine the effect of LT on gut microbiota and to determine whether gut microbiota are associated with cognitive dysfunction after LT. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after LT. Cognition (Psychometric Hepatic Encephalopathy score [PHES]), health-related quality of life (HRQOL), and stool microbiota (multitagged sequencing for diversity and taxa) tests were performed at both visits. Persistent cognitive impairment was defined as a stable/worsening PHES. Both pre-/post-LT data were compared with age-matched healthy controls. We enrolled 45 patients (56 ± 7 years, Model for End-Stage Liver Disease score 26 ± 8). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 2 months after LT with a stable course. A significantly improved HRQOL, PHES, with increase in microbial diversity, increase in autochthonous, and decrease in potentially pathogenic taxa were seen after LT compared with baseline. However, there was continued dysbiosis and HRQOL/cognitive impairment after LT compared with controls in 29% who did not improve PHES after LT. In these, Proteobacteria relative abundance was significantly higher and Firmicutes were lower after LT, whereas the reverse occurred in the group that improved. Delta PHES was negatively correlated with delta Proteobacteria and positively with delta Firmicutes. In conclusion, LT improves gut microbiota diversity and dysbiosis compared with pre-LT baseline but residual dysbiosis remains compared with controls. There is cognitive and HRQOL enhancement in general after LT, but a higher Proteobacteria relative abundance change is associated with posttransplant cognitive impairment. Liver Transplantation 23 907-914 2017 AASLD.
肝移植（LT）可改善肝硬化患者的日常功能和认知能力，但仍有一部分患者会持续存在功能障碍。肝硬化患者中存在不良微生物群或菌群失调的情况，但LT对微生物组成的影响，尤其是对肝移植后认知功能较差患者的影响尚不清楚。本研究旨在确定LT对肠道微生物群的影响，并确定肠道微生物群是否与肝移植后的认知功能障碍有关。我们纳入了等待肝移植的门诊肝硬化患者，并对他们进行随访，直至肝移植后6个月。在两次访视时均进行了认知功能（心理测量肝性脑病评分[PHES]）、健康相关生活质量（HRQOL）和粪便微生物群（多标签测序以评估多样性和分类群）检测。持续性认知障碍定义为PHES稳定/恶化。将肝移植前后的数据与年龄匹配的健康对照进行比较。我们纳入了45例患者（56±7岁，终末期肝病模型评分26±8）。他们在入组后6±3个月接受了肝移植，并在肝移植后7±2个月进行了重新评估，病程稳定。与基线相比，肝移植后HRQOL、PHES显著改善，微生物多样性增加，本土微生物增加，潜在致病分类群减少。然而，与对照组相比，29%肝移植后PHES未改善的患者在肝移植后仍存在持续的菌群失调和HRQOL/认知障碍。在这些患者中，肝移植后变形菌门相对丰度显著升高，厚壁菌门相对丰度降低，而改善组则相反。PHES的变化与变形菌门的变化呈负相关，与厚壁菌门的变化呈正相关。总之，与肝移植前基线相比，肝移植改善了肠道微生物群的多样性和菌群失调，但与对照组相比仍存在残余的菌群失调。肝移植后总体上认知功能和HRQOL有所增强，但变形菌门相对丰度变化较高与移植后认知障碍有关。《肝脏移植》2017年第23卷907 - 914页美国肝病研究学会
