Non-alcoholic fatty liver disease in 2015

There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.

Association between serumα-L-fucosidase andnon-alcoholic fatty liver disease:Cross-sectional study

AIM: To explore the association between serum α-Lfucosidase(Af U) and non-alcoholic fatty liver disease(NAf LD).METHODS: A total of 16473 individuals(9456 men and 7017 women) were included in the current study, who presented for a health examination at the first Affiliated hospital of Zhejiang University School of medicine in 2014. The baseline characteristics of the cohort were compared by NAf LD status. Linear regression analysis and stepwise multiple regression analysis were applied to assess the risk factors for NAf LD. Receiver operating characteristic curve was used to determine the sensitivity and specificity of Af U in the diagnosis of NAf LD.RESULTS: The prevalence rates of NAf LD and metabolic syndrome(met S) were 38.0% and 25.4%, respectively. The NAf LD group had significantly higher Af U levels than the non-NAf LD group(28.7 ± 7.9 U/L vs 26.0 ± 7.3 U/L, P < 0.001) and the prevalence rate of NAf LD increased with progressively higher serum Af U levels. Af U was positively correlated with met S and its five components: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure and fasting glucose. Stepwise multiple logistic regression analysis showed that Af U was associated with an increased risk of NAf LD(OR = 1.009, 95%CI: 1.003-1.014, P < 0.001). The best cut-off value of Af U for the diagnosis of NAf LD was 27.5 U/L. The area under the curve(diagnostic efficacy index) was 0.606. The sensitivity and specificity were 54.6% and 61.8%, respectively. CONCLUSION: Af U level is significantly associated with NAf LD, and elevated Af U level is an independent risk factor for NAf LD.

Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature

BACKGROUND Cholesteryl ester storage disease(CESD)is a rare genetic disease.Its symptoms and severity are highly variable.CESD is a systemic disease that can lead to the accumulation of fat and inflammation in the liver,as well as gastrointestinal and cardiovascular disease.The majority of patients require liver transplantation due to decompensated cirrhosis.Enzyme replacement therapy has been approved based on a randomized trial.Our study aims to clinically and genetically evaluate two siblings with CESD who underwent liver transplantation,as well as their first-degree family members.CASE SUMMARY The siblings were compound heterozygous for the missense variant in LIPA exon 8,c.894G>A,(p.Gln298Gln)and a single base pair deletion,c.482del(p.Asn161Ilefs*19).Analyses of single nucleotide polymorphisms showed variants with an increased risk of fatty liver disease and fibrosis for both patients.Clinically,both patients show signs of recurrence of CESD in the liver after transplantation and additional gastrointestinal and cardiovascular signs of CESD.Three family members who were LIPA heterozygous had a lysosomal acid lipase activity below the reference value.One of these carriers,a seven-year-old boy,was found to have severe dyslipidemia and was subsequently treated with statins.CONCLUSION Our study underlines that CESD is a multi-organ disease,the progression of which may occur post-liver transplantation.Our findings underline the need for monitoring of complications and assessment of possible further treatment.

“Weighing the risk”: Obesity and outcomes following liver transplantation

Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease(NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease(NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.

辅酶Q10与阿托伐他汀联合应用对冠心病伴血脂增高患者肝脏酶活性及血脂水平的影响

【目的】观察辅酶Q10（CoQ10）与阿托伐他汀联合应用对冠心病伴血脂增高患者肝脏酶活性及血脂水平的影响。【方法150例冠心病伴血脂水平增高的患者，随机分为对照组（n=25）和试验组（n=25）。对照组患者给予阿托伐他汀20mg／d，睡前服用。试验组患者在上述治疗基础上加用CoQ10 30mg／d，分3次服用。连续用药3个月，观察两组患者治疗前后体内CoQ10水平，丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）以及总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDLc）的变化。【结果】试验组治疗前后体内CoQ10含量增高，差异有显著性（P〈O．05）；ALT、AST未见显著性增高（P〉0．05）；TC、TG、LDL-C水平明显下降（P〈0．01），HDL-C水平增高，差异有显著性（P〈0．01）。对照组治疗前后体内CoQ10含量显著性降低（P〈0．01），ALT、AST水平增高，差异有显著性（P〈0．01）；血脂水平除LDL-C明显降低（P〈0．05）外，其余指标治疗后较治疗前有不同程度改变，但差异无显著性（P〉0．05）。两组治疗后CoQ10及血清转氨酶、血脂水平组间比较，差异均有显著性（P〈0．05）。【结论】外源性补充CoQ10可避免阿托伐他汀引起的转氨酶增高，并能增强他汀的降脂作用。

门冬氨酸钾镁治疗肝功能异常的临床研究

【目的】进一步观察门冬氨酸钾镁治疗肝功能异常的疗效和安全性。【方法】采用多中心随机对照研究 ,将各种急、慢性肝病患者 2 78例随机分为治疗组 ( 15 0例 )和对照组 ( 12 8例 ) ,对照组采用葡醛内酯治疗 ,治疗组采用葡醛内酯加门冬氨酸钾镁治疗。治疗前及用药 2周、4周时 ,对所有病例进行常规临床评价及肝功能试验、肾功能、血清电解质的检查。【结果】治疗 4周时 ,治疗组转氨酶改善状况优于对照组 (P <0 .0 5 ) ,胆红素改善状况亦明显优于对照组 (P <0 .0 1)。综合判定疗效 ,治疗组 2周和 4周时的显效率分别为 5 8.6 7%和79.33% ,总有效率分别为 72 .0 0 %和 89.33% ,均显著优于对照组 ( P <0 .0 5 )。针剂用药 2周后改为口服用药 ,疗效稳定 ,转氨酶及胆红素水平无反弹。【结论】门冬氨酸钾镁安全有效 。

Hepatic glycogenosis: An underdiagnosed complication of diabetes mellitus?

Hepatic glycogenosis(HG) is characterized by excessive glycogen accumulation in hepatocytes and represents a hepatic complication of diabetes that particularly occurs in patients with longstanding poorly controlled type 1 diabetes(T1D). HG has been reported to be a very rare disease, although it is believed to be extremely underdiagnosed because it is not possible to distinguish it from non-alcoholic fatty liver disease(NAFLD) unless a liver biopsy is performed. In contrast to HG, NAFLD is characterized by liver fat accumulation and is the more likely diagnosis for patients with type 2 diabetes and metabolic syndrome. The pathogenesis of HG involves the concomitant presence of insulin and excess glucose, which increases glycogen storage in the liver. HG is characterized by a transient elevation in liver transaminases and hepatomegaly. Differentiating between these two conditions is of the utmost importance because HG is a benign disease that is potentially reversible by improving glycemic control, whereas NAFLD can progress to cirrhosis. Therefore, HG should be suspected when liver dysfunction occurs in patients with poorly controlled T1 D. The aim of this article is to review the epidemiology, clinical characteristics, pathogenesis and histology of HG.

姜黄素对大鼠早期肝缺血再灌注损伤肺的保护作用

目的探讨姜黄素对大鼠肝脏缺血再灌注早期损伤（再灌注1、3h）肺的保护作用。方法将大鼠随机分为假手术组（A组）、对照组（B组）和实验组（c组）。通过检测再灌注早期肺组织病理学的改变及肺组织中SOD、CAT、MDA、MPO的含量来评价姜黄素对大鼠肝脏缺血再灌注损伤肺的保护作用。结果姜黄素可减少大鼠肝缺血再灌注损伤肺间隔的水肿和肺泡中红细胞和白细胞的渗出。姜黄素提高了早期缺血再灌注后肺组织中SOD、CAT含量，降低了肺组织中MDA、MPO含量。结论姜黄素通过抑制肺组织中的氧自由基的生成及中性粒细胞的浸润，从而在早期大鼠肝缺血再灌注损伤中起到了对肺的保护。

思连康控制大鼠酒精性肝病肠黏膜损伤的效果评价

目的 评价思连康控制大鼠急性酒精摄入致肠黏膜损伤的效果.方法 酒精灌胃诱导酒精性肝病的方法建立大鼠实验性酒精性肝病模型.取雄性Wister大鼠32只,按随机数字表法分成4组,正常组,酒精性肝病模型组,模型＋思连康组,模型＋热灭活思连康组,每组8只.检测各组大鼠血清肝功能、内毒素,检测小肠标本occludin、ZO-1.结果 酒精性肝病模型组与思连康治疗组比较,内毒素明显升高（P＜0.05）,同时occludin及ZO-1的相对表达量明显下降（P＜0.05）,而热灭活思连康同思连康活菌治疗组相比,内毒素、occludin及ZO-1差异无统计学意义（P＞0.05）.结论 益生菌合剂思连康与热灭活思连康均对大鼠实验性酒精性肝损伤有一定的控制效果.

奥曲肽对兔肝缺血再灌注后肺损伤的影响

目的 探讨奥曲肽在兔肝缺血再灌注后对远处器官肺损伤的影响.方法 采用Pring＇s兔肝脏再灌注模型,将24只新西兰大白兔随机分为三组：Ⅰ组（假手术组）、Ⅱ组（肝脏缺血再灌注生理盐水组）、Ⅲ组（奥曲肽预适应组）.Ⅲ组于腹腔内注射20μg/kg奥曲肽和皮下注射30μg/kg奥曲肽,均用0.9%的生理盐水稀释至2 ml,其他组在同一时间点用同样途径注射等量生理盐水.观察三组动物肝门阻断前（T1）、阻断后30 min（T2）、再灌注后30 min（Ts）、60 min（T4）、120 min（T5）、240min（T6）平均动脉压和心率的变化,以及T1、T2、T3、T4、T5、T6各时间点肿瘤坏死因子α（TNF-α）和白介素-1β（IL-1β）的变化,再灌注后240rain时处死兔子,取肺组织在透射电镜下观察各组肺细胞超微结构的变化,采用TUNEL法检测其凋亡细胞.结果 MAP和HR在T2至T4时间点Ⅱ组、Ⅲ组明显低于Ⅰ组,而Ⅱ组显著低于Ⅲ组（P〈0.05）;Ⅱ组从T2开始、Ⅲ组从T3开始两组血浆TNF-α、IL-β显著高于Ⅰ组（P〈0.05）,且Ⅲ组从T2开始后各时点血浆TNF-α和IL-β明显低于Ⅱ组（P〈0.01）;透射电镜下Ⅲ组肺的亚细胞结构损伤显著轻于Ⅱ组,采用TUNEL法检测肺组织中的凋亡细胞数在5个高倍镜下Ⅱ组（55.82±4.19）、Ⅲ组（32.17±3.10）明显多于Ⅰ组（3.96±0.87）,而Ⅲ组显著少于Ⅱ组（P〈0.01）.结论 奥曲肽对于兔肝缺血再灌注后远处器官肺的损伤确有保护作用.

利拉鲁肽联合二甲双胍治疗初诊2型糖尿病合并非酒精性脂肪肝的疗效观察

目的观察利拉鲁肽联合二甲双胍对初诊2型糖尿病合并非酒精性脂肪肝(NAFLD)的疗效。方法选取40例新诊断2型糖尿病合并脂肪肝患者,随机分为对照组和观察组,在生活方式干预治疗基础上,观察组给予二甲双胍500 mg口服,3次/d,利拉鲁肽注射液1.8 mg皮下注射,1次/d,对照组仅给予二甲双胍500 mg口服,3次/d,治疗12周后,对两组患者的腰围、BMI、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、总胆固醇(TC)、甘油三酯(TG)、转化生长因子β(TGF-β)及脂肪肝改善程度进行比较,判断两组患者的疗效,记录不良事件。结果与对照组比较,观察组腰围、BMI、FPG、2hPG、HbA1c、TG、TGF-β及脂肪肝程度均明显改善(P <0. 05),两组不良反应的差异无统计学意义(P>0.05)。结论利拉鲁肽联合二甲双胍对初诊2型糖尿病合并脂肪肝的患者有显著疗效。