Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites

Background/Aims: Translocation of indigenous bacterial from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats.Methods: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria.Results: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice.Conclusions: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.     

超声检查对慢性病毒性肝炎肝纤维化诊断价值的评估

目的 探索超声二维图像和多普勒血流显像对慢性病毒性肝炎患者中纤维化程度和早期肝硬化的诊断价值。方法 324例慢性病毒性肝炎患者根据肝穿刺活检组织学结果分为无肝纤维化(SO)到肝硬化(S4)五期。活检组织按炎症分级为G1～G4四级。比较各组间超声指标的差异。结果 在超声定性指标中，肝表面回声，肝实质光点形态和分布异常等指标都与肝纤维化分期和炎症分级有相关性。但这些定性指标对具体患者的诊断判断变异很大。在不同纤维化程度分组间，脾长径，脾门静脉内径在各组间差异有统计学意义。根据脾长径界限值12．1cm，诊断早期肝硬化的敏感度为60．0％，特异性为75．3％；脾静脉内径以8mm作为界限值，诊断早期肝硬化的敏感度为60．0％，特异性为78．1％；门静脉主干内径12mm，诊断早期肝硬化的敏感度76．7％，特异性44．6％。门静脉最大流速界限值为30．5cm／s时，诊断早期肝硬化的敏感度为78．6％，特异性为66．9％。结论 超声检查是诊断早期肝硬化的有效工具，是临床实用的方法，并适用于随访复查。     

苦参注射液对肝硬化患者血清、腹水纤维化及白介素的影响

目的:观察苦参注射液治疗肝硬化的疗效及其对患者血清、腹水中纤维化指标和白介素水平的影响.方法:将180例肝硬化患者随机分为两组,对照组和观察组各90例.对照组采用西医基础治疗,观察组则加载苦参注射液治疗.比较治疗前后两组患者间Child pugh分级、肝功能差异及血清、腹水中纤维化指标和白介素的水平差异.结果:2个疗程结束后观察组Child pugh分级改善率显著高于对照组;治疗3、6个月后,观察组患者血清丙氨酸转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)水平显著低于对照组,血浆白蛋白水平高于对照组,凝血酶原时间(PT)则较对照组显著缩短(P＜0.05).治疗3、6个月后,观察组血清和腹水中纤维化指标透明质酸酶(HA)、Ⅲ型前胶原肽(PCⅢ)、Ⅳ型胶原(Ⅳ-C)水平以及白介素-8(IL-8)、白介素-10(IL-10)水平均显著低于对照组(P＜0.05).结论:苦参注射液能通过抑制肝纤维化和调节机体的免疫应激反应,发挥治疗肝硬化的疗效.     

Changes in markers of hepatic steatosis and fibrosis in patients with type 2 diabetes during treatment with glucagon-like peptide-1 receptor agonists. A multicenter retrospective longitudinal study

AimsMetabolic dysfunction-associated fatty liver disease (MAFLD) is common in people with type 2 diabetes (T2D) and can progress to advanced fibrosis and cirrhosis. In this retrospective study, we explored the longitudinal changes in markers of hepatic steatosis and fibrosis during T2D treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs).MethodsWe analysed observational data from six diabetes outpatient clinics. In the whole T2D population, we calculated the hepatic steatosis index (HSI), which we previously validated against liver ultrasonography, and the Fibrosis (Fib)-4 index. We then identified patients who initiated a GLP-1RA from 2010 to 2018 and for whom data were available to evaluate changes in both HSI and Fib-4 scores over 24 months.ResultsFrom 83,116 outpatients with T2D, 41,302 (49.7%) had complete data for calculating HSI and Fib-4. Most of these T2D patients (∼70%) had MAFLD (defined as HSI>36), 9.7% of whom had advanced fibrosis based on Fib-4 thresholds. Patients with low compared to high risk of advanced fibrosis were 5-times more likely to be treated with GLP-1RA. In 535 patients who initiated a GLP-1RA, the prevalence of MAFLD based on HSI declined significantly at 6 and 24 months, but Fib-4 categories did not. HSI improved significantly only in patients receiving human-based but not exendin-based GLP-1RA, while patients concomitantly receiving metformin had less worsening in Fib-4 categories.ConclusionsMAFLD is very common among outpatients with T2D (∼70%) and the estimated prevalence of advanced fibrosis was ∼10%. Treatment with GLP-1RAs significantly improved MAFLD, but not MAFLD-associated advanced fibrosis.     

Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions

Cirrhosis causes a heavy global burden. In this review, we summarized up-to-date epidemiological features of cirrhosis and its complications. Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women, with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017. Cirrhosis caused 1.48 million deaths in 2019, an increase of 8.1% compared to 2017. Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019. The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing, while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease (NAFLD) is increasing rapidly. We described the current epidemiology of the major complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, renal disorders, and infections. We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis. In the future, NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes, and the prevalence of alcohol-induced cirrhosis is increasing. This altered epidemiology should be clinically noted, and relevant interventions should be undertaken.     

乙肝肝硬化患者门静脉宽度与门静脉血栓形成的关系

背景门静脉血栓(portal vein thrombosis,PVT)的早期诊断仍是临床上一个难题,急需要发现可早期预测诊断的无创指标.目的探讨门静脉宽度与PVT形成之间的关系.方法收集418例乙肝肝硬化患者.根据是否发生PVT分为PVT组(n=66)和非PVT组(n=352)组.比较两组患者的一般资料差异,使用多因素Logistic回顾分析影响PVT发生的危险因素.通过受试者工作特征(receiver operating characteristic,ROC)曲线评估不同危险因素预测PVT的效能.结果与非PVT组患者相比,PVT组患者的Child-Pugh评分更高、Child-Pugh A级比例更低、血小板水平更高、D-二聚体水平更高、门静脉宽度更宽、门静脉血流更慢,上述差异均存在统计学意义(P<0.05).Logistic回归显示门静脉宽度(OR=3.941,P=0.001)、门静脉血流(OR=0.841,P=0.007)、血小板水平(OR=1.024,P=0.008)和D-二聚体水平(OR=2.383,P=0.000)是肝硬化患者发生PVT的独立危险因素.门静脉宽度诊断PVT的ROC曲线下面积最大为0.874,最佳诊断值为>12.5 mm,此时的预测敏感性和特异性分别为78%和82%.结论门静脉直径增加是肝硬化患者PVT发生的危险因素,对PVT诊断具有一定价值.     

Effet protecteur de l'hémochromatose vis-à-vis des lésions vasculaires séniles ou diabétiques

Résumé I. Les lésions vasculaires non spécifiques et spécifiques du diabète ont été recherchées dans 39 cas prouvés de diabète bronzé, dans 22 cas prouvés d'hémochromatose sans diabète, dans 84 cas de cirrhose banale accompagnée de diabète franc, dans 65 cas de cirrhose banale sans diabète, chez 65 sujets normaux, et dans deux groupes de diabétiques banaux pairés individuellement pour le sexe, l'âge, la durée et la gravité du diabète ainsi que le poids corporel avec chacun des diabét ques porteurs de cirrhose banale ou de cirrhose bronzée. Un tiers des sujets a été autopsié. Le tableau 5 résume l'effet protecteur évident de l'hémochromatose dans cinq territoires artériels (rétine, reins, coronaircs, membres inférieurs, aorte) et dans deux localisations capillaires (glomérules, rétine). Cet effet protecteur est lié à l'hémochromatose et n'est pas dû à une moindre durée du diabète bronzé. La cirrhose banale a un effet protecteur beaucoup moins net (malgré sa forte tendance à l'hypocholestérolémie) vis-à-vis de la sclérose banale et vis-à-vis des effets vasculaires propres du diabète dont le degré de contrôle est cependant moins mauvais que dans l'hémochromatose. Plusieurs facteurs protecteurs liés à l'hémochromatose sontenvisagés sans qu'aucun ne paraisse décisif. II. Les deux tiers au moins des cirrhotiques banaux ont une tolérance glucidique réduite. Dans la cirrhose, les chiffres de glycémie à jeun ou post-prandiale s'échelonnent en une série continue allant de la normale au diabète insulino-dépendant (unimodalité). Comme dans la population générale les limites du diabète des cirrhotiques sont conventionelles: plus de 180 mg% deux heures après repas dans le présent travail. Le diabète ainsi défini n'est insulino-dépendant que chez le cinquième des diabétiques avec cirrhose. Cette proportion n'est pas plus élevée chez les diabétiques sans cirrhose de même âge et de même poids. Les traits cliniques du diabète qui accompagne si souvent la cirrhose banale (hérédité, évolutivité, complications typiques) ne permettent pas de le différencier du diabète commun de même gravité (glycosurie accompagnée d'hyperglycémie à jeun et deux heures après repas > 180 mg%).

---

Protective effects of haemochromatosis against micro- and macroangiopathy associated with diabetes. A comparison with common cirrhosis

Summary 1. Signs of common vascular sclerosis and of specific diabetic angiopathy have been sought in 39 cases of proved haemochromatosis with diabetes, in 22 cases of proved haemochromatosis without diabetes, in 84 cases of common cirrhosis with overt diabetes, in 65 cases of common cirrhosis without diabetes, in 65 control subjects and in two groups of patients with common diabetes, each case being carefully paired with a corresponding diabetic either with common cirrhosis or with haemochromatosis as far as sex, age, duration and severity of diabetes as well as body weight are concerned. One out of three cases has been examined at autopsy. — The striking protective effect of haemochromatosis (table 5) was confirmed in five arterial areas (retinae, kidneys, coronary, lower limbs, aorta), and in two areas where diabetic micro-angiopathy (glomeruli and retinae) is typical. This protection is closely related to haemochromatosis, and is not due to the shorter survival of patients with bronze diabetes. Common cirrhosis, despite marked hypocholesterolaemia and better control of the diabetes has but a slight protective effect. Various explanations are suggested, none of them being fully satisfactory. — 2. At least two out of three cases of patients with common cirrhosis have a reduced glucose tolerance. In cirrhosis the values of fasting and of postprandial blood sugar are widely spaced out in an unimodal pattern varying from complete normality to full insulin-dependency. Just as in the general population, the limits of diabetes are quite arbitrary (> 180 mg% two hours after a meal in the present study). According to this definition, diabetes in our series required insulin in only one out of five cases of diabetes associated with cirrhosis, no less in fact than in diabetes without cirrhosis when age and body weight were taken into account. — Clinical features (heredity, evolution, typical vascular complications) do not indicate that diabetes associated with cirrhosis differs markedly from ordinary diabetes of the same severity (glycosuria plus hyperglycaemia > 180 mg% in the fasting state or two hours after a meal).

---

Schutzeffekt der Hämochromatose gegenüber senilen und diabetischen Gefäßleiden

Zusammemfassung I. Spezifische und unspezifische Gefäßleiden des Diabetes wurden untersucht: bei 39 Fällen von Diabetes mit Hämochromatose, bei 22 Fällen von sicherer Hämochromatose ohne Diabetes, bei 84 Fällen von Zirrhose mit manifestem Diabetes, bei 65 Normalen und in zwei Gruppen von Diabetikern mit Zirrhose oder Hämochromatose, von denen jeder einzelne einer Gruppe mit denen der anderen Gruppe in Bezug auf Alter, Geschlecht, Körpergewicht, Dauer und Schwere des Diabetes vergleichbar war. Ein Drittel der Fälle wurde seziert. Die Tabelle 5 faßt den offensichtlichen Schutzeffekt der Hämochromatose auf 5 arteriellen Gefäßbezirken (Retina, Niere, Coronarien, untere Gliedmaßen, Aorta), und in zwei kapillaren Gefäßlokalisationen (Glomerulus und Retina) zusammen. Dieser Schutzeffekt beruht auf der Hämochromatose und nicht auf einer geringeren Dauer des Diabetes bei Hämochromatose. Die Zirrhose hat einen wesentlich geringeren Schutzeffekt (trotz ihrer starken Tendenz zur Hypocholesterinämie) gegenüber der Gefäßsklerose und gegenüber den spezifisch diabetischen Gefäßveränderungen. Mehrere Schutzfaktoren wurden in Erwägung gezögen, ohne daß einer von ihnen als der entscheidende angesehen werden kann. II. Mindestens zwei Drittel der gewöhnlichen Zirrhotiker haben eine verminderte Glukosetoleranz. Bei der Zirrhose erstrecken sich die Blutzuckerwerte, nüchtern oder postprandial, kontinuierlich zwischen den Normwerten und Werten, wie sie bei Insulinbedürftigkeit angetroffen werden. In dieser Arbeit werden die Grenzen des Diabetes bei Zirrhose entsprechend den Konventionen für die allgemeine Bevölkerung angesetzt: mehr als 180 mg% zwei Std. nach der Mahlzeit. Der so definierte Diabetes ist nur bei jedem fünften Diabetiker mit Zirrhose insulinbedürftig. Dieses Verhältnis ist bei Diabetikern ohne Zirrhose des gleichen Alters und Körpergewichtes nicht größer. Die klinischen Erscheinungen des Diabetes, welcher die Zirrhose so häufig begleitet, (Heredität, Verlauf, typische Komplikationen) erlauben es nicht, ihn von dem allgemeinen Diabetes gleichen Schweregrades (Glykosurie mit Hyperglyzämie nüchtern und zwei Std. nach den Mahlzeiten über 180 mg%) zu unterscheiden.