小柴胡汤治疗肝病的药理研究

报告小柴胡汤对诱导干扰素及对肝炎、肝硬化、肝癌、肝损伤、脂肪肝的较好作用。

Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.

Stem cells for end stage liver disease: How far have we got?

End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.

Efficacies of β-L-D4A against Hepatitis B virus in 2.2.15 cells

AIM： To investigate the antiviral effect of beta-L- enantiomer of 2;3＇-didehydro-2＇,3″-dideoxyadenosine （13-L-D4A） on 2.2.15 cells transfected with the hepatitis B virus （HBV） genome.METHODS： Lamivudine （3TC） as a positive control. Then, HBV DNA in treated 2.2.15 cells and the Hepatitis B surface antigen （HBsAg） in the culture supernatants were detected to determine the inhibitory effect of β-L- D4A. At the same time, 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） was used to detect the survival ratio of 2.2.15 cells.RESULTS： β-L-D4A has a dose-dependent inhibitory effect on HBV DNA replication; this effect was apparent when the concentration was above 1 mol/L. When β-L- D4A was at the highest concentration, 100 mol/L, the HBsAg inhibition ratio was above 50%. The Therapeutic index （TI） of β-L-D4A was above 2.1.CONCLUSION： β-L-D4A has a dose-dependent inhibitory effect on the replication of HBV DNA and the secretion of HBsAg at low toxicity,

N-acetyl cysteine therapy in acute viral hepatitis

AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P＞0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon:An open-label pilot study

AIM： To investigate the use of high dose consensusinterferon in combination with ribavirin in former iv drug users infected with hepatitis C. METHODS： We started, before pegylated （PEG）interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon （CIFN） and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 μg of CIFN daily for 8 wk, followed by 9 μg daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72. RESULTS： More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively, showing a negative qualitative PCR [genotype 1 fourteen patients （56%）, genotype 2 five （50%）, genotype 3 thirteen （87%）, genotype 4 four （50%）]. Forty-eight percent of genotype 1 patients showed sustained virological response （SVR） six months after the treatment. CONCLUSION： CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy （EOT） rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GTI and high viral load or for non-responders after failure of standard therapy.

THE ROLE OF RECOMBINANT HUMAN FUSION PROTEIN IL－6／IL－2（CH925） IN HEPADNA VIRUS INFECTION TREATMENT

The effects of CH925, a novel immune modulator, on hepadna virus infection was evaluated. Day-old ducklings were inoculated intravenously with LJ-76 DHBV containing serum. Infected ducklings were then treated with the CH925 and the mixture of IL-2 and IL-6 intravenously and the control ducklings received equivalent normal saline (NS). Blood and liver samples were taken and assayed for DHBV DNA and /or DHBsAg. At the completion of the experiment there was a inhibition of viremia with the CH925 and IL-2 + IL-6. Serum DHBV DNA was detected in 6 of 10 ducks in 100 000 unit/kg dosage group, 7 of 10 ducks in 50 000 unit/kg dosage group and 6 of 10 ducks in IL-2 + IL-6 dosage group, compared with 9 of 10 NS control, and it showed a similar result in circulating DHBsAg. When samples of liver DNA were processed for hybridization, a little difference in the DHBV DNA replication was noted between ducks receiving CH925, IL-2 + IL-6 or NS placebo. It is suggested that CH925 might be a potential remedy in HBV infection treatment.

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。