|关键词||非酒精性脂肪性肝病 非酒精性脂肪性肝炎 小肠细菌过度生长 氢呼气试验 甲烷呼气试验 口忙传输时间|
|其他题名||The value of hydrogen and methane breath test to detect SIBO on exploring the role of intestinal flora in the incidence|
背景：非酒精性脂肪性肝病(nonalcoholic fatty liver disease，NAFLD)是指除外酒精及其他明确的损肝因素所致的、以弥漫性脂肪变性为特征的临床病理综合征。NAFLD的病理生理是多因素的，其中机械、化学、免疫、生物肠道屏障的功能在NAFLD的发展过程中是相互联系、密不可分的，一旦肠黏膜屏障被破坏，肠道细菌及其产物将移位到肝脏并引起一系列免疫和炎症反应，这将导致NAFLD的发展与形成。且越来越多的证据表明肠道微生态紊乱，尤其是小肠细菌过度生长(small intestinal bacterial overgrowth，SIBO)可能在非酒精性脂肪性肝病的发病机制中起重要作用。氢呼气试验作为一种非侵入性的检查手段，是目前用于诊断SIBO的主要方法。SIBO时小肠细菌发酵碳水化合物除产生H2外，还产生CH4、CO2，研究发现约1/3的成人肠腔内有产甲烷细菌，若仅用氢呼气试验诊断SIBO患者会出现假阴性结果，国外有文献认为甲烷呼气可联合氢呼气作为SIBO的补充诊断，从而减少SIBO的漏诊率。目前已有研究表明氢呼气试验诊断SIBO在非酒精性脂肪性肝病患者中检出率高，而甲烷呼气试验在NAFLD患者中的应用国内外尚未见报道，本研究加入甲烷呼气试验，以了解肠道中产甲烷菌对NAFLD患者的影响。
结果：1. NAFLD患者的SIBO阳性率（86.70%）明显高于健康对照组（18.70%）（P＜0.05），氢（甲烷）呼气试验阳性率均明显高于健康对照组（P＜0.05），且表现为全程的呼气氢（甲烷）浓度升高；2. 与双阴性（即H2-CH4-）相比，NAFLD组中单纯氢呼气试验阳性者（H2+CH4-）、单纯甲烷呼气试验阳性者（H2-CH4+）及双阳性者（即H2+CH4+）均高于健康对照组，差异有统计学意义（P＜0.05），其中H2+CH4-所占比例最高，H2-CH4+占22%；3. 非酒精性脂肪性肝炎（NASH）患者SIBO的阳性率为100%，而SIBO阴性者无一例为NASH。其中NASH患者氢呼气试验阳性率（100.00%）高于非酒精性单纯性脂肪肝（NAFL）患者（54.30%）（P＜0.05），且表现为全程呼气氢浓度升高，在0-60min有统计学差异（P＜0.05）；NASH患者甲烷呼气试验阳性率(30.00%)低于NAFL(40.00%)，且表现为全程呼气甲烷浓度降低，但差异无统计学意义（P＞0.05）；4. 合并代谢综合征（MS）的NAFLD患者SIBO阳性率(90.50%)略高于未合并MS的NAFLD患者(83.30%)，但无统计学差异（P＞0.05）；5. 80.00%NASH患者合并MS，明显大于NAFL患者（34.30%）（P＜0.05）；6. NAFLD组患者OCTT（口盲传输时间）为（106.71±30.04min）与对照组（84.38±12.09min）相比明显延长。SIBO阳性的NAFLD患者OCTT较SIBO阴性的NAFLD患者及健康对照组明显延长（P＜0.05）。NAFLD患者中甲烷呼气试验阳性者（H2-CH4+/H2+CH4+）的OCTT较甲烷呼气试验阴性者（H2-CH4-、H2+CH4-）及健康对照组均明显延长，结果有统计学差异（P＜0.05）。NAFLD患者中单纯氢呼气试验阳性者（H2+CH4-）OCTT较健康对照组无显著差异（P＞0.05）；7.NAFLD患者的腹围、BMI明显大于对照组（P＜0.05），其中肥胖的患者甲烷呼气试验阳性检出率明显高于无肥胖者（P＜0.05），而氢呼气试验阳性的检出率较无肥胖者无明显差异（P＞0.05）。
结论: 1.同时应用氢呼气及甲烷呼气试验可以提高NAFLD患者SIBO的检出率；2. NAFLD患者中氢呼气试验及甲烷呼气试验阳性率均高，以氢呼气试验阳性更为明显；3.氢呼气试验阳性的NAFLD患者NASH发生率更高，而甲烷呼气试验阳性则与NASH的发生无明显相关；4.合并代谢综合征的患者更容易发生NASH；5.甲烷呼气试验阳性的NAFLD患者口盲传输时间明显延长，且与肥胖相关。
Backgrounds: Nonalcoholic fatty liver disease (NAFLD) is a clinical syndrome that acterized by diffuse fatty degeneration, while except alcohol and other specific liver damage factors. The Pathophysiology of NAFLD is multiple factors, including mechanical, chemical, immune and intestinal barrier function, which is mutual connection and inseparable in the process of the development of NAFLD. Once the intestinal mucosal barrier is broken, the intestinal bacteria and their products will shift to the liver and cause a series of immune reaction and inflammation, which will lead to the development of NAFLD. A number of evidence suggests that the intestinal microecological disturbance, especially small intestinal bacterial overgrowth (SIBO) may play an important role in the pathogenesis of NAFLD. Hydrogen breath test as a non-invasive examination , is currently the main methods used to diagnose SIBO in clinical practice. When SIBO is broken, hydrogen will be produced by bacteria as a consequence of carbohydrate fermentation could be messured in the intestine after oral ingestion of glucose and lactulose, as well as methane and carbon dioxide. A study found that about one third of adults have methanogens in the lumen, if only use hydrogen breath test in the diagnosis in patients with SIBO will lead to false negative results. Foreign author believes that methane breath can ally hydrogen breath as a supplement diagnosis of SIBO, thereby reducing the missed diagnosis of SIBO. Existing studies have shown that SIBO, diagnosised with hydrogen breath test, was high in patients with NAFLD.While the application of methane breath test in patients with NAFLD has not been reported previeously. In this study, we add the methane breath test to explore the impact of the intestinal methanogens in patients with NAFLD.
Objects: To observe the performance of hydrogen and methane breath test in the NAFLD. To explore the influence of SIBO on liver function in patients with NAFLD and the occurrence of SIBO in NAFLD with metabolic syndrome.To provide the basis for the treatment of patients with NAFLD.
Method: To 45 cases that diagnosed NAFLD outpatients in the digestive Department and preventive medical of our hospital from Sep.2015-Apr.2016 randomly. With the exception of viral hepatitis, drug-induced liver disease, total parenteral nutrition, liver degeneration, autoimmune liver disease, by completing the abdominal ultrasound examination, the examination such as screening for hepatitis B virus infection and autoimmune antibody. 45 cases of patient were included, 20 males and 25 females , aged from 20 to 75 years old (54.00±14.82) years. 16 healthy subjects as control, including 7 males and 9 females , aged from 23 to 65 years old (43.13±13.00) years. To through the questionnaire survey complete demographic information, diet, lifestyle and always complications. To measure the abdominal perimeter, weight, height, and calculate BMI. Liver function, blood lipid, blood glucose were examined and performenced lactulose hydrogen and methane breath test.
Results:1. The positive rate of SIBO in NAFLD patients (86.70%) was higher than that of healthy controls(18.70%) (P<0.05), of which the positive rate of hydrogen (methane) breath test were significantly higher than that of control group (P < 0.05), and shown the whole test points hydrogen (methane) concentration increased. 2. To contrasted with the double negative (named H2-CH4-), the one that pure hydrogen breath positive in patients with NAFLD (named H2+CH4-), the one that pure methane breath positive (named H2-CH4+), and the one that double positive(named H2+CH4+),were all higher than the healthy control, the results had statistical difference (P<0.05), of which the H2+CH4- accounted for the highest proportion, and the H2-CH4+ accounted for 22%. 3. The SIBO positive in NASH was 100%, while the patients of SIBO negatie had no NASH. The positive rate of hydrogen breath test in NASH (100.00%) were higher than NAFL(54.30%), and appeared for the entire hydrogen concentration was increased, it was statistically difference from 0 to 60 min (P < 0.05); the positive rate of methane breath test in NASH (30.00%) were lower than the NAFL (40.00%), and performanced for all the methane concentration was reduced, the result had no statistical difference (P>0.05). 4. The positive rate of SIBO in NAFLD patients combined metabolic syndrome group (90.50%) was higher than that of uncombined (83.30%) (P>0.05). 5. The proportion of NASH patients with MS (80.00%) was significantly higher than that of NAFL (34.30%) (P < 0.05). 6. The OCTT of NAFLD group (106.71±30.04min) was delayed obviously compared with control (84.38±12.09min). The OCTT of SIBO positive patients with NAFLD was significantly longer than the SIBO negative in NAFLD patients and healthy controls (P < 0.05). In patients with NAFLD, the OCTT of methane breath test positive (H2-CH4+/H2+CH4+) were significantly longer than methane breath test negative（H2-CH4-/H2+CH4-） and control group, the results have statistical difference (P < 0.05).The OCTT had no significant difference between the patients of H2+CH4 and the controls (P > 0.05).7. The abdominal perimeter and BMI of NAFLD patients were significantly higher than the heathy control (P < 0.05), of which the methane positive rate of obese patients was significantly higher than no obesity (P < 0.05), meanwhile the positive rate of hydrogen breath test had no obvious difference with the one no obesity (P > 0.05).
Conclusion: 1. To detection both of hydrogen and methane gas at the same time could increase the positive rate of SIBO; 2.The positive rate of of hydrogen and methane breath were both significantly increased (mainly hydrogen breath positive); 3. The incidence of NASH was higher in NAFLD patients of Hydrogen breath test positive, while there was no obvious correlation between the positive rate of methane breath test with the incidence of NASH; 4. The patients with metabolic syndrome were more likely to occur NASH; 5. There was delayed OCTT in NAFLD patients of methane breath test positive , which was associated with obesity.
|乔蕾. 氢和甲烷呼气试验检测SIBO对探讨肠道菌群在非酒精性脂肪性肝病发病中作用的价值[D]. 北京大学第四临床医学院. 北京大学,2016.|