Serum ornithine carbamyltransferase reflects hepatic damage in diabetic obese mice

Background and Aim: As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity in several models, it is important to confirm its application to the diagnosis of non‐alcoholic fatty liver disease. Methods: C57BL/6, KK‐Ta and KK‐Ay mice were fed a high‐fat diet for 8 weeks and serum enzyme markers were examined. Serum OCT and alanine aminotransferase (ALT) were also measured in diabetic obese ob/ob and db/db mice fed a normal diet. Liver damage in these mice was evaluated by the hepatic content of tumor necrosis factor‐alpha. Results: Serum levels of OCT increased in KK‐Ay fed a high‐fat diet compared with the normal diet‐fed group, whereas C57BL/6 and KK‐Ta mice were not affected. In ob/ob mice, the relative increase was always greater in OCT than in ALT. In contrast, in db/db mice, the relative increase was always greater in ALT. Hepatic tumor necrosis factor‐alpha was significantly elevated in ob/ob mice, but not in db/db mice. Conclusions: Serum OCT seemed to reflect tumor necrosis factor‐alpha‐mediated hepatic damage when compared with ALT in diabetic obese mice and could be useful in the application for non‐alcoholic fatty liver disease with features of metabolic syndrome, such as obesity and diabetes.     

Garcinia cambogia,Either Alone or in Combination With Green Tea,Causes Moderate to Severe Liver Injury

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丙氨酸氨基转移酶快速检测在血站血液采集前应用的意义研究

目的：探究丙氨酸氨基转移酶（ALT）快速检测在血站血液采集前应用的意义。方法以2014年5月—2014年8月血站采集的血液样本为研究对象,作为实验组。实验组在采集血液样本前进行ALT快速检测,统计血液报废情况;以2013年5月—2013年8月血站采集前未行ALT快速检测的血液样本为对照组,统计报废情况。对照组与实验组结果进行对比。对已知ALT阳性和ALT阴性的样本各10例,这20例样本均进行ALT快速检测和实验室检测,比较两种检验的结果。结果血站采集血液前进行ALT快速检测血液报废率为1.54%,结果低于未进行ALT快速检测的血液报废率7.08%,差异有统计学意义(<0.05)。ALT快速检测与实验室检测结果差异无统计学意义（P>0.05）。结论 ALT快速检测结果准确性高,在血站血液采集前应用ALT快速检测可以降低血液报废率,值得临床推广应用。     

A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients

Aim:

To develop a population pharmacokinetic (PopPK) model of tacrolimus in healthy Chinese volunteers and liver transplant recipients for investigating the difference between the populations, and for potential individualized medication.

Methods:

A set of 1100 sparse trough concentration data points from 112 orthotopic liver transplant recipients, as well as 851 dense data points from 40 healthy volunteers receiving a single dose of tacrolimus (2 mg, po) were collected. PopPK model of tacrolimus was constructed using the program NONMEM. Related covariates such as age, hepatic and renal functions that were potentially associated with tacrolimus disposition were evaluated. The final model was validated using bootstrapping and a visual predictive check.

Results:

A two-compartment model of tacrolimus could best describe the data from the two populations. The final model including two covariates, population (liver transplant recipients or volunteers) and serum ALT (alanine aminotransferase) level, was verified and adequately described the pharmacokinetic characteristics of tacrolimus. The estimates of V2/F, Q/F and V3/F were 22.7 L, 76.3 L/h and 916 L, respectively. The estimated CL/F in the volunteers and liver transplant recipients was 32.8 and 18.4 L/h, respectively. Serum ALT level was inversely related to CL/F, whereas age did not influence CL/F. Thus, the elderly (≥65 years) and adult (<65 years) groups in the liver transplant recipients showed no significant difference in the clearance of tacrolimus.

Conclusion:

Compared with using the sparse data only, the integrating modeling technique combining sparse data from the patients and dense data from the healthy volunteers improved the PopPK analysis of tacrolimus.     

Incidence of Hepatitis C Virus Infections Among Users of Human Immunodeficiency Virus Pre-exposure Prophylaxis

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Impact of Hepatitis A vaccination with a two-dose schedule in Panama: Results of epidemiological surveillance and time trend analysis

PurposeIn April 2007, Panama introduced Hepatitis A universal vaccination using a two-dose schedule (Havrix^® junior; GSK Vaccines, Belgium). We assessed the impact of this hepatitis A vaccine three years after it was recommended for universal mass vaccination in Panama.Materials and methodsHepatitis A vaccination impact was assessed using two different approaches. The first approach used retrospective data (incidence and number of cases for all age groups), collected from the passive surveillance of the Epidemiologic Surveillance System of the Ministry of Health of hepatitis A and unspecified hepatitis before (2000–2006) and after (2008–2010) introduction of hepatitis A vaccine. The second approach was a prospective hospital-based active surveillance for hepatitis cases conducted in subjects (0–14years) during 2009–2011 at three sentinel hospitals in Panama.ResultsOverall, the annual incidence of hepatitis A and unspecified hepatitis in 2008, 2009 and 2010 were 13.1, 7.9 and 3.7 per 100,000 subjects, lower than the baseline incidence of 51.1 per 100,000 subjects. In comparison to the mean baseline period (2000–2006), there was an 82% mean reduction in the overall hepatitis-related outcomes (hepatitis A and unspecified hepatitis) after vaccine introduction (2008–2010) in all age groups.In the hospital-based surveillance (2009–2011), of the 42 probable viral hepatitis A cases, nine cases were confirmed as acute hepatitis A (8 in 2009, 1 in 2010). Of these confirmed cases, two belonged to the targeted vaccine group (1–4 years) but were not vaccinated.ConclusionsOur study suggests that the introduction of two-dose hepatitis A vaccines in Panama has contributed to the reduction in the incidence of overall hepatitis-related outcomes for all age groups, suggesting herd protection. Additional monitoring is required to document a sustained long-term effect.