Hyperalbuminemia and elevated transaminases associated with high-protein diet

While high protein diets are increasing in popularity, there is a lack of data on their potential adverse effects. We describe two patients on high protein supplements and exercising for physical fitness. Both developed intermittent abdominal pain, transient elevations in transaminases and hyperalbuminemia without there being any identifiable cause. The symptoms and abnormalities on the laboratory tests resolved after the high protein intake was discontinued. While the pathogenesis and importance of these abnormalities need further study, the findings raise concerns regarding the safety of high protein diets combined with high intensity exercise.     

Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers

AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93 M diet, and animals in the experimental group received an Atkins-based diet(59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation(sd) assuming unpaired and parametric data; we analyzed differences using the student's t-test. statistical significance was set at P 0.05.RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.     

Randomized clinical trial of standard dietary treatment versus a low-carbohydrate/high-protein diet or the LighterLife Programme in the management of obesity*

Background: With the current obesity epidemic, the search for effective weight loss approaches is required. In the present study, changes in weight, body composition and cardiovascular (CV) risk in response to a low‐fat, reduced‐energy diet (LFRE), a low‐carbohydrate/high‐protein diet (LCHP), or a commercially available very low‐calorie diet (LighterLife; LL) were assessed. Methods: One hundred and twenty obese patients (body mass index ≥35 kg/m²) underwent a screening period of 3 months on the LFRE. Those who lost >5% of their body weight were maintained on this approach for an additional 3 months, whereas those who lost >10% at this time were maintained for 1 year. Patients failing to achieve these targets were randomly allocated to either the LCHP (n = 38) or LL (n = 34) for a period of 9 months. Results: Significantly greater weight loss was seen for patients on the LL than the LCHP at 3 (mean (±SD) ?11.6 ± 12.9 vs ?2.8 ± 4.5 kg, respectively; P < 0.0001) and 9 months (?15.1 ± 21.1 vs ?1.9 ± 5.0 kg, respectively; P < 0.0001) after screening. Significantly greater improvement in total cholesterol, low‐density lipoprotein–cholesterol, fasting glucose, and diastolic blood pressure was seen at 3 months in patients on the LL compared with the LCHP (P < 0.05). These differences were no longer significant at 9 months, with the exception of fasting glucose. The attrition rate was elevated in the LCHP group, but did not differ significantly from the LL group. Conclusion: Greater weight loss and improved CV risk were achieved with the LL, which mostly reflects the patient support provided for each dietary treatment.     

饮食干预对胰岛素抵抗大鼠肝脏组织蛋白激酶B表达的影响

目的在高脂饮食诱导胰岛素抵抗的基础上,观察饮食干预调整对胰岛素抵抗大鼠肝脏蛋白激酶B蛋白（protein kinase B,PKB）表达的影响。方法选取雄性Wistar大鼠30只,分为正常对照组10只,给予低脂饲料;模型组20只,给予高脂饲料。模型组大鼠给予高脂喂养5周后,分为2组：高脂喂养组10只,继续高脂饮食;低脂喂养组10只,给予低脂饮食。干预6周后,蛋白印迹法检测大鼠肝脏组织中胰岛素刺激PKB的蛋白表达含量。结果 （1）5周后,高脂喂养组空腹血糖、胰岛素、三酰甘油、胆固醇及胰岛素抵抗指数（homeostasismodel assessment-insulin resistance index,HOMA-IR）明显升高,胰岛素敏感指数（insulin resistance index,ISI）显著下降,差异有统计学意义（P〈0.01）,出现了胰岛素抵抗,造模成功。（2）低脂饮食干预6周后,与高脂饮食组比较,低脂喂养组大鼠的空腹血糖、三酰甘油、胆固醇及HOMA-IR下降,ISI升高,差异有统计学意义（P〈0.05）。（3）高脂喂养组大鼠肝脏组织中PKB的表达水平明显低于对照组,减少了23.5%,两组PKB表达比较,差异有统计学意义（7.34±0.19 vs.8.97±0.20,t=9.335,P〈0.001）;低脂饮食干预6周后,低脂喂养组PKB蛋白较高脂喂养组增加4.9%,两组比较,差异有统计学意义（7.70±0.18 vs.7.34±0.19,t=10.102,P〈0.001）。结论长期高脂饮食可诱导出胰岛素抵抗,低脂干预后纠正糖脂代谢紊乱,改善胰岛素抵抗,可能与增加肝脏组织中PKB蛋白表达有关。     

高动物蛋白饮食对高血压患者血管功能及心血管危险因素的影响

目的 调查高血压患者的生活方式,了解高动物蛋白饮食对血管功能和颈动脉内膜中层厚度等心血管危险因素的影响。方法 在我院心血管门诊选取符合纳入标准的高血压患者88例,通过问卷调查方式获取参与者的一般生活方式,检测肱动脉血流介导的血管舒张功能（FMD）和肱踝脉搏波传导速度,同时收集患者颈动脉内膜中层厚度（IMT）等一般临床资料,分析高动物蛋白饮食与血管功能及颈动脉内膜中层厚度等心血管危险因素的相关性。结果 男性52例,女性36例,年龄中位数42 (38, 53)岁。平均动脉压中位数106 (97, 112) mmHg,最高平均动脉压中位数123 (116, 132) mmHg。FMD中位数5.1 (3.8, 7.3)%,IMT中位数0.9 (0.8, 1.2) mm。在日常饮食中,偏向于高动物蛋白饮食的39例,比较均衡的36例;高动物蛋白饮食与FMD显著负相关,与IMT显著正相关;而且,动物蛋白摄入量较大的受试者倾向于存在更大的心血管风险。结论 高血压患者在接受有效降压治疗的同时,应采取健康的生活方式,均衡饮食,避免过高的动物蛋白摄入量,可能有助于降低心血管疾病风险。     

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

AIM:To identify the proportion,causes and the nature of drug-induced liver injury(DILI) in patients with notably elevated alanine aminotransferase(ALT).METHODS:All the inpatients with ALT levels above 10 times upper limit of normal range(ULN) were retrospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period.Relevant clinical information was obtained from medical records.Alternative causes of ALT elevations were examined for each patient,including biliary abnormality,viral hepatitis,hemodynamic injury,malignancy,DILI or undetermined and other causes.All suspected DILI cases were causality assessed using the Council for International Organizations of Medical Sciences scale,and only the cases classified as highly probable,probable,or possible were diagnosed as DILI.Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors.RESULTS:A total of 129 cases with ALT 10 ULN were identified.Hemodynamic injury(n = 46,35.7%),DILI(n = 25,19.4%) and malignancy(n = 21,16.3%) were the top three causes of liver injury.Peak ALT values were lower in DILI patients than in patients with hemodynamic injury(14.5 ± 5.6 ULN vs 32.5 ± 30.7 ULN,P = 0.001).Among DILI patients,one(4%) case was classified as definite,19(76%) cases were classified as probable and 5(20%) as possible according to the CIOMS scale.A hepatocellular pattern was observed in 23(92%) cases and mixed in 2(8%).The extent of severity of liver injury was mild in 21(84%) patients and moderate in 4(16%).Before discharge,10(40%) patients were recovered and the other 15(60%) were improved.The improved patients tended to have a higher peak ALT(808 ± 348 U/L vs 623 ± 118 U/L,P = 0.016) and shorter treatment duration before discharge(8 ± 6 d vs 28 ± 12 d,P = 0.008) compared with the recovered patients.Twenty-two drugs and 6 herbs were found associated with DILI.Antibacterials were the most common agents causing DILI in 8(32%) cases,followed by glucocorticoids in 6(24%) cases.Twenty-four(96%) cases received treatment of DILI with at least one adjunctive drug.Agents for treatment of DILI included anti-inflammatory drugs(e.g.,glycyrrhizinate),antioxidants(e.g.,glutathione,ademetionine 1,4-butanedisulfonate and tiopronin),polyene phosphatidyl choline and herbal extracts(e.g.,protoporphyrin disodium and silymarin).Diagnosis of DILI was not mentioned in the discharge letter in 60% of the cases.Relative to prevalent cases and cases from wards of internal medicine,incident cases and cases from surgical wards had a higher risk of missed diagnosis in discharge letter [odds ratio(OR) 32.7,95%CI(2.8-374.1),CONCLUSION:DILI is mostly caused by use of antibacterials and glucocorticoids,and constitutes about one fifth of hospitalized patients with ALT 10 ULN.DILI is underdiagnosed frequently.     

Endoscopic retrograde cholangiopancreatography and liver biopsy in the evaluation of elevated liver function tests after liver transplantation

BACKGROUND Abnormal liver function tests(LFTs) in post-liver transplant(LT) patients pose a challenge in the timing and selection of diagnostic modalities.There are little data regarding the accuracy of endoscopic retrograde cholangiopancreatography(ERCP) and liver biopsy(LB) in diagnosing post-transplant complications.AIM To evaluate the diagnostic performance of ERCP and LB in patients with nonvascular post-LT complications.METHODS This single-center retrospective study evaluated patients undergoing both ERCP and LB for evaluation of elevated LFTs within 6 mo of LT from 2000 to 2017.Diagnostic operating characteristics including accuracy,sensitivity and specificity for various diagnoses were calculated for ERCP and LB.The R factor(ratio of alkaline phosphatase to alanine aminotransferase) was also calculated for each patient.RESULTS Of the 1284 patients who underwent LT,91 patients(74.7% males,mean age of 51)were analyzed.Anastomotic strictures(AS,24.2 %),acute cellular rejection(ACR,11 %) and concurrent AS/ACR(14.3 %) were the most common diagnoses.ERCP carried an accuracy of 79.1%(95 % CI:69.3-86.9),LB had an accuracy of 93.4%(95 % CI:86.2-97.5),and the combination of the two had an accuracy of 100%(95 % CI:96-100).There was no difference between patients with AS and ACR in mean R factor(AS:1.9 vs ACR:1.1, P=0.24).Adverse events did not differ between the two tests(ERCP:3.1% vs LB:1.1%,P=0.31).CONCLUSION In patients with abnormal LFTs after LT without vascular complications,the combination of LB and ERCP carries low risk and improves diagnostic accuracy over either test alone.     

低蛋白饮食治疗早期慢性肾功能不全的临床观察

目的:观察分别以低蛋白面粉(含蛋白质0·9%,热卡344Kcal/100g)为主食和普通大米、面粉为主食的不同低蛋白饮食治疗早期慢性肾功能不全的疗效。方法:病情稳定的慢性肾功能不全患者60例,均符合以下条件:(1)原发病为原发性肾小球疾病,血清肌酐(SCr)1·3~3·0mg/dl;(2)年龄18~70岁,性别不限;(3)原发疾病无明显活动迹象,双肾缩小;(4)尿蛋白<1·5g/24h,尿红细胞<50万/ml;(5)血压控制低于140/90mmHg。原发疾病仍有活动或伴有严重贫血、营养不良、感染、出血、肝功能不全、心功能不全及糖尿病患者不入选。患者随机分为低蛋白面粉饮食组(n=30)和普通低蛋白饮食组(n=30),观察6个月。两组蛋白质摄入量0·6g/(kg·d),以鸡蛋、牛奶、瘦肉等优质蛋白质,补充主食以外摄入不足的蛋白质部分,保证热卡摄入量30~35Kcal/(kg·d)(按理想体重计算)。由专人个体化制订每周食谱,定期饮食指导,并通过每月连续3日饮食记录表,调查和计算患者的实际营养素摄入量。观察两组治疗前后人体测量参数、血生化、尿蛋白定量等指标,计算饮食蛋白质摄入量(DPI)和肾小球滤过率(GFR)。结果:(1)病例退出原因:两组各有5例患者退出研究,其中治疗组2例不耐受长期服用面食、要求改用大米,2例常不能在家中就餐、无条件按要求烹调低蛋白面粉,另1例外地患者因面粉携带不便、拒用;对照组4例未能按制订的食谱控制饮食,蛋白质摄入过多,另1例未按要求随访;(2)两组各有25例完成研究,治疗组和对照组DPI分别为(0·61±0·02)g/(kg·d)和(0·63±0·04)g/(kg·d),两组无差异;(3)两组患者治疗前后体重、体重指数、臂中肌周径和上臂围均无显著变化;(4)对照组总蛋白、白蛋白和前白蛋白轻度下降(P>0·05),治疗组保持稳定;(5)治疗组BUN下降明显(P<0·01),对照组无下降。治疗组SCr显著下降,对照组在2个月和4个月时SCr上升(P<0·05),但至6个月时与基础值无差异;治疗组GFR上升(P<0·05),而对照组在2个月和4个月时GFR下降(P<0·05),但在6个月时与基础值无差异;两组GFR下降的速率分别为-0·31(ml/min·1·73m2)/月和0·28(ml/min·1·73m2)/月。(6)治疗组尿蛋白定量下降,对照组无明显变化,治疗前尿蛋白定量升高的患者中治疗组和对照组分别有7/13(53·8%)和4/15例(26·7%)降至正常范围(P>0·05)。结论:6个月的初步研究表明,以低蛋白面粉为主食的优质低蛋白饮食对肾功能和尿蛋白的疗效优于普通低蛋白饮食,营养状况稳定,患者的顺应性和耐受性好。     

Adiponectin knockout mice on high fat diet develop fibrosing steatohepatitis

Background and Aim:  Low levels of serum adiponectin have been reported to be associated with obesity, diabetes, and non-alcoholic steatohepatitis (NASH), as well as several malignancies. Adiponectin knockout (KO) mice have been reported to cause insulin resistance and neointimal formation of the artery. We used adiponectin KO mice fed a high fat (HF) diet, and investigated the effect of adiponectin on the progression of steatohepatitis and carcinogenesis in vivo .
Methods:  Adiponectin KO mice and wild type (WT) mice were fed a HF diet or normal chow for the periods of 24 and 48 weeks. The HF diet contained 60% of calories from fat.
Results:  The adiponectin KO mice on the HF diet showed obesity, marked elevation of serum transaminase levels, and hyperlipidemia. At 24 weeks, hepatic expression of tumor necrosis factor-α and procollagen α (I) was higher in KO mice as compared with WT mice. At 48 weeks, liver triglyceride contents in KO mice on normal chow were significantly higher than those in WT mice. Hepatocyte ballooning, spotty necrosis, and pericellular fibrosis around central veins were observed in KO mice on the HF diet. The pericellular fibrosis was more severe in KO mice on the HF diet than that in WT mice (1.62% vs 1.16%, P  = 0.033). Liver adenoma and hyperplastic nodules developed in a KO mouse on the HF diet at 48 weeks (12.5%, n  = 1/8), whereas no tumor was detected in WT mice ( n  = 10).
Conclusions:  Adiponectin may play a protective role in the progression of NASH in the early stages by suppressing tumor necrosis factor-α expression and liver fibrosis.     

Assessing the Burden of Abnormal LFTs and the Role of the Electronic Health Record: A Retrospective Study

Background

Primary care clinicians encounter abnormal liver function tests (LFTs) frequently. This study assesses the prevalence of abnormal LFTs and patient follow-up patterns in response.

不同饮食及运动方案对非酒精性脂肪性肝病患者的影响

非酒精性脂肪性肝病(NAFLD)发病率逐年攀升,目前已是全球最常见的肝脏疾病之一。合理的饮食及运动是目前公认的治疗NAFLD最为关键的一步,也是管理NAFLD患者的基石,但是,由于各种客观原因,不同国家、地区、学会对NAFLD患者制定的饮食及运动方案不尽相同。对近年来不同国家、地区及不同文献所报道的干预NAFLD患者的饮食及运动方案作一综述,以期为临床医生指导NAFLD患者制订合理的饮食及运动策略提供依据。     

Mediterranean diet and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet(MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and antioxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.     

Dietary supplementation in patients with alcoholic liver disease：a review on current evidence

BACKGROUND: Alcoholic liver disease (ALD) is one of the main causes of liver disease worldwide. Although the patho-genesis of ALD has not yet been well elucidated, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxy-gen species play a pivotal role in the clinical and pathological spectrum of the disease. This review summarizes the existing evidences on dietary supplements considered to have antioxi-dant, and/or anti-inlfammatory properties, and their role in the management of ALD and the proposed mechanisms.
DATA SOURCES: The present study reviewed all studies pub-lished in PubMed, ScienceDirect and Scopus, from 1959 to 2015, indicating the role of different dietary supplementation in attenuation of many pathophysiological processes involved in development and progression of ALD. Full-texts of citations were used except for those that were published in languages other than English.
RESULTS: Signiifcant progress has been made to understand the key events and molecular players for the onset and pro-gression of ALD from both experimental and clinical studies;however, there is no successful treatment currently available. The present review discussed the role of a variety of dietary supplements (e.g. vitamin A, carotenoids, vitamins B3, C and E, in addition to antioxidants and anti-inlfammatory agents) in treating ALD. It has been shown that supplementation with some carotenoids, vitamin B3, vitamin C, silymarin, curcumin, probiotics, zinc, S-adenosylmethionine and garlic may have potential beneifcial effects in animal models of ALD; however, the number of clinical studies is very limited. In addition, sup-plementation should be accompanied with alcohol cessation.
CONCLUSIONS: Since oxidative stress and inlfammation are involved in the pathogenesis of ALD, dietary supplements that can modulate these pathologies could be useful in the treat-ment of ALD. In addition to alcohol cessation, these supple-ments have shown beneifcial effects on animal models of ALD. Clinical trials are needed to validate the beneifciary role of these supplements in patients with ALD.     

Hepatotoxicity associated with Garcinia cambogia: A case report

BACKGROUND Herbal supplements(HS) for weight loss are perceived to be "safe" and"natural", as advertised in ads, however, hepatotoxicity can be associated with consumption of some HS. Use of HS may be missed, as the patient may not report these unless specifically asked about these products, since they are often not thought of as medications with potential side effects or interaction potential.CASE SUMMARY We reported a case of a 21-year-old female with morbid obesity who presented with abdominal pain for 1 wk associated with nausea, vomiting, anorexia and myalgias. She denied smoking tobacco, drinking alcohol, usage of illicit drugs,hormonal contraceptives, or energy drinks. There was no significant past medical or family illnesses. Her laboratory workup revealed acute liver failure. The workup for possible etiologies of acute liver failure was unremarkable. She was using a weight loss herbal supplement "Garcinia cambogia" for 4 wks. This case demonstrates the association of acute liver failure with Garcinia cambogia.CONCLUSION Medical reconciliation of HS should be performed in patients with suspected acute liver failure and early discontinuation of HS can prevent further progression of drug induced hepatoxicity.     

High protein diets decrease total and abdominal fat and improve CVD risk profile in overweight and obese men and women with elevated triacylglycerol

Background and aimsIt is unclear whether high protein weight loss diets have beneficial effects on weight loss, abdominal fat mass, lipids, glucose and insulin compared to conventional low fat diets in subjects at increased risk of cardiovascular disease (CVD) because of elevated glucose and triglyceride concentrations. Our objective was to determine the effects of high protein (HP) compared to standard protein (SP) diets on CVD risk in obese adults.Methods and resultsData from three, 12 week, randomized parallel trials with subjects assigned to either HP or SP diet (5500–6500 kJ/day) were pooled. Weight, body composition (dual energy X-ray absorptiometry), lipids, insulin and glucose were measured before and after weight loss. Data from 215 subjects (49.9 ± 9.8 years, BMI 33.5 ± 3.7 kg/m²), 108 HP, 107 SP were analyzed. Weight loss (HP diet 7.82 ± 0.37 kg; SP diet 7.65 ± 0.39 kg, NS) and total fat loss were not different (HP 6.8 ± 4.3 kg; LP 6.4 ± 4.7 kg, NS on intention to treat analysis). The reduction in triacylglycerol (TAG) was greater on HP than SP 0.48 ± 0.07 mmol/L vs 0.27 ± 0.06 mmol/L, (P < 0.001). Subjects with TAG greater than the median (>1.54 mmol/L at baseline) lost more weight (HP 8.5 ± 0.6; SP 6.9 ± 0.6 kg, P = 0.01, diet by TG group), total (HP 6.17 ± 0.50 kg; SP 4.52 ± 0.52 kg, P = 0.007) and abdominal fat (HP 1.92 ± 0.17 kg; SP 1.23 ± 0.19 kg, P = 0.005) on HP. Total cholesterol (12 vs 6%, HP vs SP) and TAG (39 vs 20%, HP vs SP) decreased to a greater extent in these subjects (both P ≤ 0.05) on HP.ConclusionShort-term high protein weight loss diets had beneficial effects on total cholesterol and triacylglycerol in overweight and obese subjects and achieved greater weight loss and better lipid results in subjects at increased risk of CVD. These observations provide further information regarding the utility of this dietary approach in effectively managing body weight and composition and reducing CVD risk in overweight and obese individuals.