Renal safety of adefovir dipivoxil for two-year treatment in Chinese patients with chronic hepatitis B / 中华临床感染病杂志

Objective To assess the renal safety of adefovir dipivoxil (ADV) in Chinese patients with chronic hepatitis B (CHB).Methods A retrospective study was performed on 1 013 CHB patients from Chinese ADV multicenter clinical trials (ADF30001 and ADF106632).All patients were administrated with ADV 10 mg daily.The serum creatinine and phosphorus levels were measured in different time pointsduring 104-week treatment.Nephrotoxicity was defined as an increase ≥44.2 μ mol/L from baseline in serum creatinine or a serum phosphorus value of ＜ 0.4845 mmol/L on two consecutive occasions.Paired t test was used to analyze serum creatinine and phosphorous data before treatment and at different time points during treatment.Results At week 28,week 52,week 80 and week 104,the median levels of serum creatinine were 74.963,76.996,76.820 and 77.969 μmol/L,respectively,and there were no significant differences from baseline (t =0.91,0.23,0.59 and 0.97,P ＞ 0.05).No patient experienced a ≥ 44.2 μmol/L increase from baseline.For serum phosphorus,the median levels at week 28,week 80 and week 104 were 1.098,1.088 and 1.048 mmol/L,and there were significant decreases from baseline (t =2.34,3.06 and 4.94,P ＜0.05 or ＜ 0.01).The cumulative incidence of serum phosphorus abnormality was 0.8％ (8/104).There were no confirmed serum phosphorous decreases to ＜ 0.4845 mmol/L.Conclusion Two years treatment with ADV (10 mg/d) does not result in marked nephrotoxicity,indicating that ADV 10 mg daily is well tolerated by Chinese patients.

Intravenous Rabeprazole Sodium for Treatment of Duodenobulbar Ulcer Bleeding:A Multicenter,Randomized, Double-blind,Positive Drug Parallel-group Controlled Clinical Study / 胃肠病学

Background:To date,clinical studies on intravenous rabeprazole sodium for treatment of duodenobulbar ulcer bleeding are still lacking.Aims:To evaluate the efficacy and safety of intravenous rabeprazole sodium with different doses and times of administration in treating patients with duodenobulbar ulcer bleeding.Methods:A multicenter,randomized, double-blind,positive drug parallel-group controlled trial was performed.One hundred and five patients with duodenobulbar ulcer bleeding proved by gastroscopy were randomly divided into four groups.Patients in group A,B and C were treated with intravenous rabeprazole sodium 20 mg qd,40 mg qd and 20 mg bid for 5 days,respectively.Patients in control group received intravenous omeprazole sodium 40 mg bid for 5 days.Hemostatic rate was the primary endpoint,hemostatic time and amount of blood transfusion were the secondary endpoints.Results:Hemostatic rates in group A,B,C and control group were 96.2% (25 /26),92.6% (25 /27),100.0% (26 /26)and 100.0% (26 /26),respectively,no significant difference was seen between the four groups (P >0.05).Median hemostatic time in group A,B,C and control group were 24 (24,72)h,24 (24,72)h,24 (24,48)h and 24 (24,48)h,respectively,no significant difference was seen between the four groups (P >0.05).No patient need blood transfusion during the treatment course.Slight leucopenia was the exclusive adverse effect seen in one case in group C after accomplishment of treatment.Conclusions:Three intravenous rabeprazole sodium regimens with different doses and times of administration were all effective and safe for treatment of mild to moderate duodenobulbar ulcer bleeding.Administration with 20 mg bid seems more effective among the three regimens.

The relationship between fatty liver disease and liver metastases from colorectal cancer / 中华消化杂志

Objective To evaluate the relationship between fatty liver disease and liver metastases from colorectal cancer.Methods Eight hundred and ninety patients with colorectal cancer,who were submitted to hospital from 1993 to 2002 and had complete clinical data,were retrospectively analyzed.Of 890 patients,127 were diagnosed as fatty liver(FL)by ultrasonography,and the other 763 who were without fatty liver were served as controls(NFL).The clinical data including pathology,liver matastasis or mortality after surgery were analyzed.The survival rate and liver matastasis after surgery were followed up and statistically analyzed.Results The liver metastases was lower in FL group than that in NFL group(7 cases vs 102 cases,P=0.012).The tumor size was smaller in FL group than that in NFL group[(4.15±1.80)crn vs(4.77±2.25)cm,P=0.0016].The Dukes B(247/732,33.74%)and C(232/732,31.83%)patients were more common in NFL group,whereas Dukes A(41/121,33.61 %)and B(40/121,32.77%)were more common in FL group with significant difference(P＜0.05).No significant difference was found in 7-year survival rate between two groups who had been followed up(P=0.3024).Conclusion The lower incidence of liver metastases is found in FL group,which indicate that fatty liver disease may inhibit liver metastases from colorectal cancer by underlying mechanisms.

The expression of metabolism related genes in patients of non-alcoholic fatty liver diseases with cholelithiasis / 中华消化杂志

Objective To study the expression of metabolism related genes in peripheral blood mononuclear cells in patients of non alcoholic fatty liver diseases (NAFLD)with cholelithiasis.Methods Patients who had BMI ≥ 27 were divided into obese ( n = 10),the NAFLD ( n = 7) and NAFLD with cholelithiasis (n= 16) groups.The subjects who had BM1<25 (n = 10) and cholelithiasis (n = 16) were served as controls.The expression of peroxisome proliferator-activated receptors (PPAR)α,sterol regulatory element-binding protein(SREBP)-lc and Leptin Rb in peripheral blood mononuclear cells were measured.Results The expressions of PPARα,SREBP-lc and Leptin Rb in peripheral blood mononuclear cells were different in five groups.The significant difference was found in expression of leptin Rb between NAFLD with cholelithiasis group and the obese group,NAFLD with cholelithiasis group and the cholelithiasis group,NAFLD with cholelithiasis group and NAFLD group,the obese group and controls (P values= 0.037,0.050,0.044and 0.038,respectively).The leptin Rb mRNA expression in NAFLD with choletethiasis group was the lowest.Conclusions The low expression of leptin Rb mRNA was found in NAFLD patients with cholelithiasis.Cholelithiasis may increase the extent of insulin resistance and cause NAFLD progression.

An extended two-year trial of lamivudine in Chinese patients with chronic hepatitis B / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the long-term efficacy and safety of lamivudine therapy for the treatment of chronic hepatitis B and the clinical influence of emergence of tyrosine methionine aspartic acid (YMDD) motif mutation of hepatitis B virus (HBV).</p><p><b>METHODS</b>This multicenter, double-blind, randomized, placebo controlled trial began in 1996. A total of 429 patients with HBsAg, HBeAg and HBV CNA positives were enrolled. They were randomized to receive either lamivudine 100 mg daily (n = 322) or placebo (n = 107) on 3 : 1 ratio for the first 12 weeks. Thereafter all patients were offered open label lamivudine treatment and assessed every 4 weeks for a total of 104 weeks.</p><p><b>RESULTS</b>After 1 year treatment 72.7% patients (285/392) had a sustained serum HBV DNA response. HBV DNA continued to be substantially suppressed at the second year, except in patients with the emergence of YMDD mutation whose mean HBV DNA levels increased to 86 Meq/ml (bDNA assay) but were much more lower than that of pre-treatment baseline level. lamivudine therapy resulted in increased HBeAg loss and HBeAg/anti-HBe seroconversion, which were correlated with both baseline alanine transaminase (ALT) levels and also with duration of lamivudine treatment. HBeAg loss was achieved in 26.8% of patients with ALT > 1-fold upper limit of normal at 2 yeas and in 35.6% and 55.6% of patients with ALT > 2-fold upper limit of normal and ALT > 5-fold upper limit of normal, respectively. For HBeAg seroconversion, these figures were 17.4%, 22.2%, and 33.3% respectively. By the end of 2 years, ALT levels were remained in normal ranges in 50.3% whose ALT were abnormal before treatment, and in 83% whose ALT were mormal before treatment. YMDD mutation were developed in 49.7% of the patients. Their serum HBV DNA levels were slightly increased to bDNA median level 86 Meq/ml and 15% of the patients they were ALT exceeded baseline levels. Four patients clinically flared-up and recovered after stop treatment. The adverse drug reactions (ADRs) of lamivudine were mild to moderate, only two patients were reported as drug related severe ADR.</p><p><b>CONCLUSION</b>Sustained HBV replication and clinical improvement could be obtained by the long-term lamivudine therapy with good tolerance and safety.</p>

Prophylactic and therapeutic effect of oxymatrine on D-galactosamine-induced rat liver fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the prophylactic and therapeutic effect of oxymatrine on experimental liver fibrosis and to reveal its mechanism.</p><p><b>METHODS</b>By establishing D-galactosamine-induced rat liver fibrosis model, we observed the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGF?1 mRNA and changes of tissue pathology.</p><p><b>RESULTS</b>There was a decline of liver hydroxyline and serum AST and ALT in oxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was (0.50 0.11)mug/mg compared with (0.99 0.14)mug/mg in D-GalN group (t=8.366, P<0.01). The content in oxymatrine treatment group was (0.44 0.04)mug/mg compared with 0.70 0.06 in D-GalN group (t=9.839, P<0.01). The SOD activity was (149.81 15.28) NU/mg in oxymatrine pretreatment group and (95.22 16.33) NU/mg in the model group (t=7.309, P<0.01); (157.68 19.54) NU/mg in the treatment group compared with (119.88 14.94) NU/mg in the model group (t=4.348, P<0.01). MDA in the pretreatment group was (2.06 0.17) nmol/mg, lower than (4.57 0.37) nmol/mg in the model group (t=17.529, P<0.01). In the treatment group, it was (1.76 0.24)nmol/mg, lower than (3.10 0.17) nmol/mg in the model group (t=12.697, P<0.01). TGF?1 mRNA reduced in the pretreatment and treatment groups as compared with that in the model group (0.21 0.01 vs 0.50 0.01, t=48.665, P<0.01; 0.18 0.02 vs 0.38 0.01, t=22.464, P<0.01). Electron microscopy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the model group. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necrosis and pseudo-nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions were much improved.</p><p><b>CONCLUSIONS</b>Oxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liver fibrosis. This is partly by protecting hepatocyte and suppressing fibrosis accumulation through anti-lipoperoxidation.</p>

Effect of reduced glutathione on the proliferation,oxidative stress and transforming growth factor?1 expression of human hepatic stellate cells / 中华消化杂志

Objective To investigate the impact of reduced glutathione(GSH) on the prolifera- tion,oxidative stress and transforming growth factor?1(TGF-?1) expression of human hepatocytes and hepatic stellate cells(HSCs)(LX-2 cell line).Methods Human hepatocytes and HSCs were incubated with various concentrations of GSH(0.5—50 mmol/L or 0.5—10 mmol/L).The effects of GSH on the proliferation of hepatocytes and HSCs were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphennyhera- zolium bromide colorimetric assay.Human hepatocytes and HSCs were co-cultured with GSH and ferric nitrilotriacetic acid,superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents were detected.HSCs were incubated with high(5.0 mmol/L),media(2.5 mmol/L) and low (0.5 mmol/L) concentrations of GSH,the expressions of TGF-?1 mRNA and protein were detected by ELISA and real- time PCR.Results In concentration ranged from 2.5 to 10 mmol/L,the GSH could promote the pro- liferation of hepatocytes but no HSCs,significantly increased the activity of SOD and decrease the con- tents of MDA in hepatocytes and HSCs,and inhibited the expression of TGF-?1 in HSCs.Conclusions GSH can not only promote the proliferation of hepatocytes,but also protect hepatocytes and HSCs from oxidative stress,and inhibit the secretion of TGF-?1 in HSCs.GSH may play a role in hepatocellular protection,antioxidation and anti-fibrosis.

The application of psychometric measures in diagnosis of minimal hepatic encephalopathy / 中华消化杂志

Objective To establish the normal parameters of psychometric measures such as the number connection tests A(NCT-A)and digit symbol tests(DST)in assessment of minimal hepatic en- cephalopathy(MHE).Methods One hundred and sixty healthy volunteers(aged 25 to 64 years;educa- tional level＞9 years)were divided into＜35 ys,35～44 ys,45～54 ys and 55～64 ys groups.All of the healthy volunteers were assessed with NCT-A and DST to establish the normal value of age-related parameters,which can be used for diagnosis of MHE in patients with liver cirrhosis.Two standard devi- ation of the normal mean was used as a diagnostic criterion for MHE.One hundred and six cirrhotic patients were assessed with these parameters.Results The parameters of NCT-A were(25.1?4.6) sec in＜35 ys group,(32.1?6.8) sec in 35～44 ys group,(38.6?7.1)sec in 45～54 ys group or (49.3?6.3)sec in 55～64 ys group.The scores of DST were 49.9?4.7 in＜35 ys group,44.6?4.8 in 35～44 ys group,38.5?5.0 in 45～54 ys group or 35.4?4.7 in 55～64 ys group.Thirty one out of 106 cirrhotic patients were diagnosed as MHE based on these parameters.Conclusion The NCT- A and DST are psychometric assessments for diagnosis of MHE.Age-based normal paramerters of NCT- A and DST are needed to be established.

An experimental study of prophylactic and therapeutic effects of oxymatrine on dimethylnitrosamine-induced rat liver fibrosis / 中华消化杂志

Objective To investigate the prophylactic and therapeutic effect of oxymatrine(OM) on experimental liver fibrosis and to reveal its mechanism. Methods By establishing models of dimethylnitrosamine(DMN) induced liver fibrosis in rats, we observed the effect of oxymatrine on liver/weight index, serum and tissue biochemical indexes, content of liver hydroxyproline, expression of TGF?1 mRNA, electromicroscopic changes and tissue pathology. Results There was a decline of serum AST, ALT and liver hydroxyproline in oxymatrine group, compared to those of the DMN group( P

The inhibitory effect of oxymatrine on hepatitis B virus in vitro / 中华消化杂志

Objective To study the inhibitory effect of oxymatrine on hepatitis B virus(HBV) in vitro. Methods Microparticle enzyme immunoassay, bDNA signal amplification assay was used for determining secrected HBsAg/HBeAg in the culture medium, HBV DNA from core particles in the cytoplasm and MTT colorimetric assay was used to assay the oxymatrine cytotoxity. Results The inhibitory rates of HBsAg and HBeAg were 40.57% and 48.27% by oxymatrine at the concentration of 2 000 ?g/ml. At 100～2 000 ?g/ml, it can remarkably decrease the level of viral core associated HBV DNA in the cytoplasm. No significant toxicity was shown in such concentrations. Conclusion Oxymatrine has a potential anti HBV activity in vitro.

The clinical study of the therapy of potassium L-aspartate injection on hypokalemia / 中国实用内科杂志

Objective Estimating clinical effects of the Therapy of Potassium L-aspartate Injection on Hypokalemia.Methods These hypolalemia patients from the Renji hospital of Shanghai Jiaotong University and Other Two Hospitals,and from March 2007 to May 2008,which were caused from various kinds of reasons.The test group (42 patients) were intravenous dripped by using three rami potassium L-aspartate injection added in 5% Glucose (or saline) 750 mL,the control group (44 patients) were gived two rami chloratum Kalium injection added in 5% Glucose (or saline) 750 mL,the Kalium were 1.10 g/d in both groups,once per day,time of therapy was 7 day.Results The test and control groups effective power after therapy were 86.67% and 91.11%,respectively,there was no significant difference (P=0.3998).The Kalium dose of test group was advanced from (3.18?0.23) mmol/L before testing to (3.73?0.37) mmol/L after therapy,the elevated average was (0.61?0.46)mmol/L,and there was no significant difference (P=0.4722).The accumulation power of Kalium recovery were (51.11?7.45)%,(77.78?6.20)%,(86.67?5.07)%,at the second,the fored and the sevened day,respectively.There was no significant difference between the two groups (P=0.1430).Conclusion The clinical effect was correspond between three rami potassium L-aspartate injection added in 5% Glucose (or saline) 750 ml and the Isodose chloratum Kalium injection,by once per day,and seven days of therapy,which can treat hypokalimeia caused from various kinds of reasons.