[Clinical analysis of de novo HBV infection after liver transplantation in non-HBV- related liver disease].

Objective: The aim of this study was to summarize and analyze the clinical features and characteristics of de novo HBV infection after liver transplantation in non-HBV-related liver disease. Methods: We retrospectively analyzed the clinical data of 13 patients with new HBV infection in 376 cases of liver transplantation patients with non-HBV related liver diseases from April 2002 to December 2013 in our hospital. Results: Among 376 patients with non-HBV-related liver disease after liver transplantation, 13 patients developed new HBV infection, and the rate of new HBV infection was 3.46%. Of the 13 cases, 5 were males and 8 were females. The follow-up time was 14.7 -128.7 months, and the average time from surgery to new HBV infection was 19.06 months. The primary diseases were as follows: 5 cases of primary biliary cholangitis, 3 cases of alcoholic liver disease, 2 cases of drug-induced liver damage, 1 cases of post-hepatitis C cirrhosis, congenital biliary atresia and congenital liver fibrosis. All patients were positive for HBsAg, HBeAg, anti-HBc, 11 were positive for HBV DNA, and 2 were negative for HBV DNA. 6 cases had abnormal liver function and 7 cases had normal liver function. All patients were treated with antiviral therapy with nucleoside (acid) analogues. HBsAg was negative in 6 patients; HBsAg remained positive in 7 cases, including HBsAg, HBeAg, anti-HBc positive in 6 cases, HBsAg, anti-HBe, anti- HBc was positive in 1 case, HBV DNA was still positive in 1 patient, and HBV DNA was negative in 6 patients; liver function was normal in all patients. Conclusion: Non-HBV- related liver transplantation are high-risk group of new HBV infection, with the highest incidence of autoimmune liver disease. It is speculated that it may be related to the long-term use of hormones after the transplantation. The prognosis of newly diagnosed HBV infection after liver transplantation is fine as long as it can be found and treated early.

[Risk factors for hepatitis B recurrence after liver transplantation for HBV-related liver disease].

Objective: To investigate the risk factors for hepatitis B recurrence after liver transplantation for HBV-related liver disease, and to provide a basis for effective preventive measures. Methods: A retrospective analysis was performed for the clinical data of 907 patients with HBV-related liver disease who underwent liver transplantation from April 2002 to December 2013. The chi-square test was used to determine the risk factors for hepatitis B recurrence, and multivariate Cox regression analysis was used for identifying the independent risk factors. Results: There were 907 patients with HBV-related liver disease who underwent liver transplantation. The patients were followed up for 1-144 months, with a median follow-up time of 50.9 months. Among them, 56 experienced hepatitis B recurrence, yielding a recurrence rate of 6.17%. The univariate analysis showed that positive HBeAg before surgery, positive HBV DNA before surgery, positive anti-HBc in liver donor, postoperative tumor recurrence, and postoperative regimen for the prevention of hepatitis B recurrence were significantly correlated with hepatitis B recurrence after liver transplantation (P < 0.05). The multivariate Cox regression analysis showed that positive HBeAg before surgery (OR = 1.891, 95% CI 1.064-3.360, P < 0.05), positive anti-HBc in liver donor (OR = 3.128, 95% CI 1.591-6.151, P < 0.01), and postoperative tumor recurrence (OR = 4.365, 95% CI 2.152-8.857, P < 0.01) were independent risk factors for hepatitis B recurrence. Conclusion: Positive HBeAg before surgery, postoperative tumor recurrence, and positive anti-HBc in liver donor are independent risk factors for hepatitis B recurrence after liver transplantation. For the patients who plan to undergo liver transplantation, antiviral therapy should be given before surgery to reduce HBV viral load, and effective preventive measures after surgery are the key to the prevention and reduction of postoperative hepatitis B recurrence.

OCT demonstrating neoatherosclerosis as part of the continuous process of coronary artery disease.

Although the advent of drug-eluting stents has reduced the rates of target vessel revascularization, there are observations of ongoing stent failure occurring very late after stent implantation and presenting as very late restenosis or as very late stent thrombosis. The de novo development of atherosclerosis within the neointimal region, called neoatherosclerosis, has been identified as one of the pathomechanisms of these observed late stent failures. The mechanisms of neoatherosclerosis development and its association with stent failure are currently the subject of intensive research. Optical coherence tomography (OCT) is an invasive imaging modality that allows us to visualize the micromorphology of coronary arteries with near-histological resolution, thus providing detailed assessment of the morphological characteristics of the neointima after stent implantation, including neoatherosclerosis. Several OCT studies have tried to provide in vivo insights in the mechanisms of neoatherosclerosis development and its association with late stent failure. This review summarizes the current insights into neoatherosclerosis obtained with OCT and discusses the association of neoatherosclerosis with late stent failure.

Clinical outcome of drug-eluting versus bare-metal stents in patients with calcified coronary lesions: a meta-analysis.

BACKGROUND: The relative safety and efficacy of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with calcified coronary lesions is still debated. AIMS: To evaluate clinical outcome of DES versus BMS in patients with calcified coronary lesions using a meta-analysis of the current literature. METHODS: We performed a systematic literature search using Medline, Embase, Cochrane and several other databases. Randomised controlled trials, prospective and retrospective cohort studies with a mean follow-up period >6 months were included. Primary efficacy was target lesions revascularisation (TLR) and primary end-point for safety was stent thrombosis. Secondary end-points were cardiac death and recurrent myocardial infarction (MI). RESULTS: Five trials were included in the meta-analysis, including 2440 patients (1230 in the DES group, 1210 in the BMS group). TLR was significantly lower in patients treated with DES as compared with patients treated with BMS (8.5% vs 16.0%; odds ratio (OR) = 0.50; 95% confidence interval (CI) 0.38-0.65; P < 0.00001). There were no significant differences in the incidence of stent thrombosis (0.9% vs 0.3%; OR = 2.01; 95% CI 0.34-11.88; P = 0.44), cardiac death (3.3% vs 4.2%; OR = 0.81; 95% CI 0.50-1.30; P = 0.38) and recurrent MI (5.0% vs 5.2%; OR = 0.99; 95% CI, 0.66-1.49; P = 0.97) between the two groups. Subgroup analysis by the sample size and follow-up duration showed that the associations were similar between DES versus BMS. CONCLUSIONS: DES significantly reduces TLR rates as compared with BMS in patients with calcified coronary lesions, with non-significant differences in terms of stent thrombosis, cardiac death and MI.

Post-marketing surveillance study with iodixanol in 20 185 Chinese patients from routine clinical practices.

OBJECTIVE: To determine the incidence of immediate and delayed adverse drug reactions (ADRs), and to assess patient discomfort following administration of iodixanol during imaging examinations in routine clinical practice. METHODS: A total of 20 185 patients across 95 clinical centres were enrolled in a prospective post-marketing surveillance registry with iodixanol. Patients were monitored for occurrence of ADRs immediately following iodixanol administration and for up to 7 days after administration. RESULTS: The overall rate of ADRs was 1.52%, of which 0.58% was immediate and 0.97% was delayed onset. Two patients had non-fatal serious ADRs (0.01%). The ADRs were significantly more common in patients who underwent contrast-enhanced CT/coronary CT angiography vs others (p < 0.001), in those receiving pre-heated iodixanol vs non-heating (p < 0.001), in those aged 70 years or younger (p < 0.001), in those in whom a power injector was used for contrast delivery (p < 0.001) and in those with a history of an allergic reaction to contrast (p = 0.024). Multivariate analysis showed that female gender, intravenous route of contrast injection, body weight ≥ 80 kg, age less than 65 years, contrast flow rate ≥ 4 ml s⁻¹ and prior reaction to iodinated contrast medium were all significant and independent contributors to ADRs. Pre-treatment contrast volume and history of cardiac disease, gout, hypertension, diabetes mellitus or asthma did not affect the rate of ADRs. Discomfort was generally mild, with 94.8% of patients reporting a composite score of 0-3. CONCLUSION: The safety of iodixanol in routine clinical practice was shown to be similar to the published safety profiles of other non-ionic iodinated contrast agents. Patient discomfort during administration was mild or absent in most patients. ADVANCES IN KNOWLEDGE: The major strength of this study is that it included 20 185 patients enrolled in various types of imaging examinations. The safety profile of iodixanol was comparable to previously published work.

Geochemistry and environmental assessment of major and trace elements in the surface sediments of the Wei River, China.

The development of western China in the past decade has led to increased discharges of wastewater and river pollution. The Wei River is the largest tributary of the Huang He River, but its geochemistry has not been thoroughly investigated. Sixty-three bed-surface sediment samples were collected from the Wei and analyzed for 24 elements by WDXRF; objectives for the study were to investigate the geochemical properties of the sediments; identify sources, and assess pollution levels and environmental risks. Major and trace element concentrations were comparable with those in other large rivers in China, but potentially hazardous trace elements (PHTEs) were lower than in the Yangzi or Pearl Rivers; most likely due to dilution of contaminants by the large sand inflows into the Wei and a lower level of industrialization. Nonetheless, pollution and risk analyses demonstrate slight contamination of Cr, Mn, Nb, Ni and Zn, moderate contamination of Cu and Pb, and strong contamination of As at some locations. Adverse biological effects from Ni and Cu are possible and are likely from As. Statistical and spatial analyses indicate that agriculture runoff and industrial wastewater discharge contribute to the contamination of this river. A comprehensive environmental management strategy, realistic national standards for wastewater discharge, and rigid enforcement are needed to address river pollution in China.

Potential implication of activating killer cell immunoglobulin-like receptor and HLA in onset of pulmonary tuberculosis.

Killer cell immunoglobulin-like receptor (KIR) and human leucocyte antigen (HLA) play crucial role in maintaining immune homoeostasis and controlling immune responses. To investigate the influence of KIR and HLA-C ligands on the risk of pulmonary tuberculosis (PTB), we studied 200 patients who were confirmed to have PTB and 200 healthy controls on the different frequencies of KIR and HLA-C ligands. Genotyping of these genes was conducted by sequence-specific primer polymerase chain reaction (SSP-PCR) method. Gene frequencies were compared between PTB group and the control group by χ(2) test, and P < 0.05 was regarded as statistically significant. As a result, the frequency of KIR genotype A/B was increased in PTB than controls but A/A was decreased. Moreover, striking differences were observed in the frequencies of HLA-Cw*08 between the two groups. Besides, the frequencies of '2DL2/3 with C1' in PTB were increased compared with control group. In addition, individuals with no KIR2DS3 and no Cw*08 were higher in controls than in PTB. KIR2DS1 was increased in PTB when HLA-C group 2 alleles were missing. In conclusion, KIR and HLA-C gene polymorphisms were related to susceptibility to PTB.

Genetic variation in thrombin-activatable fibrinolysis inhibitor is associated with the risk of diabetic nephropathy.

Diabetic nephropathy is a kidney disease or damage that results as a complication of diabetes, especially Type 2 diabetes, while albuminuria is an early marker for diabetic nephropathy as it can predict cardiovascular events and mortality in diabetic patients. A potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. We investigated the associations of the activity-related variants in the TAFI coding gene (505A/G,1040C/T) with the risk of diabetic nephropathy by examining 297samples including 140 health controls and 157 confirmed diabetic nephropathy patients. Diabetic nephropathy grades were further categorized by the urine albumin excretion (UAE)-to-creatinine ratios (ACR). We found little difference that was statistically significant in terms of 505A/G among patients and controls. While at 1040C/T, the detected frequency for the T allele in the group of diabetic nephropathy patients was significantly smaller than that of the control group (15.6% vs 25.7%, respectively; p<0.05). This was due to the relative decrease of T/T homozygotes in the patients (p<0.05, 95% odds ratio 0.28, confidence interval 0.11-0.70). Surprisingly, the difference was only observed with initial diabetic nephropathy stages. This study clearly indicates that, at 1040C/T, the frequency for the T allele is strongly associated with increased risk for diabetic nephropathy in a subset of the general population, implying that the T allele confers protection against the onset of diabetic nephropathy only in homozygosity and may function as a recessive trait.

Association of killer cell immunoglobulin-like receptors with pulmonary tuberculosis in Chinese Han.

Killer cell immunoglobulin-like receptors (KIRs) are involved in the pathogenesis of a variety of diseases. However, whether KIR polymorphism is associated with susceptibility to pulmonary tuberculosis was unknown. We examined a possible association of KIR polymorphism with susceptibility to pulmonary tuberculosis in Chinese Han. We analyzed 15 KIR genes in 109 pulmonary tuberculosis patients and 110 healthy controls using sequence-specific primer PCR analysis of genomic DNA. We found that the frequencies of KIR2DS1, 2DS3 and 3DS1 were significantly higher in patients than in the control group. In addition, the number of subjects carrying more than two activating KIR genes in the patient group was significantly higher than in the control group. The gene cluster containing KIR3DS1-2DL5-2DS1-2DS5 was also significantly more frequent in the patient group. In conclusion, KIR genes 2DS1, 2DS3 and 3DS1 appear to be associated with resistance to pulmonary tuberculosis in the Chinese Han population. KIR genes apparently have a role in resistance to pulmonary tuberculosis.

PI-3K/AKT signal pathway modulates vascular smooth muscle cells migration under cyclic mechanical strain.

BACKGROUND: The migration of vascular smooth muscle cells (VSMCs), exposed to altered mechanical strain, contributes to vascular remodeling which is the key event underlying the pathogenesis of vascular diseases such as atherosclerosis and restenosis. Signal transduction pathways in VSMCs activated by mechanical strain that influence cell migration remain unclear. Herein, we provide evidence that higher mechanical strain enhances VSMCs migration, which is mediated, at least in part, through Akt/protein kinase B (PKB) included pathway. MATERIAL AND METHODS: VSMCs were exposed to mechanical strain at 15 % elongation and 5 % elongation, 60 cycles/min using FX-4000T system from at least three independent experiments. VSMCs were incubated with 100nmol/L wortmannin, 10 uM Akti, 10 uM PD98059 and 10 uM SB202190 prior to strain for inhibitor studies, respectively. VSMCs migration,the activation of Akt/PKB, the inhibition of STI-571 and immunofluorescence for actin fibers were detected, respectively. Activation of the Akt pathway and inhibition of STI-571 were assessed with the Western blot technique. RESULTS: (1) Our study demonstrated that VSMCs migration under 15 % strain was facilitated compared with 5 % strain (15 % strain vs. 5 % strain, P < 0.01); and the activation of P-Akt was enhanced compared to the control (15 % strain and 5 % strain vs. static control, P < 0.01, respectively); whereas wortmannin could markedly inhibit serine/threonine kinase Akt/PKB phosphorylation, reduced VSMCs migration following higher mechanical strain stimulation (15 % strain + wortmannin vs. 15 % strain, P < 0.01). Immunofluorescence revealed actin rearrangement, which could also be inhibited by wortmannin in VSMCs induced by cyclic strain. (2) Akti significantly inhibited VSMCs migration (15 % strain + Akti and 5 % strain + Akti vs. static control, P < 0.05,respectively), neither PD98059 nor SB202190 inhibited VSMCs migration (5 % strain + PD98059 or +SB202190 vs. static control, P < 0.01; 15 % strain + PD98059 or +SB202190 vs. static control P < 0.01,respectively). (3) Higher mechanical strain inhibits STI-571 activity in VSMCs (5 % strain vs. static control, P < 0.05; 15 % strain vs. static control, P < 0.01). CONCLUSIONS: Our data shows that higher mechanical strain activated-Akt/PKB is required for VSMC migration and probably functions through its effects on actin rearrangement.

Screening for liver cancer: results of a randomised controlled trial in Qidong, China.

OBJECTIVES: To investigate the effectiveness of screening for liver cancer in reducing mortality from the disease in a high-risk population in China. SETTING: A randomised controlled trial was carried out among men aged 30-69 who were chronic carriers of hepatitis-B virus (HBsAg positive) during the period 1989-1995 in Qidong county, Jiangsu Province, China. METHODS: 5581 HBsAg carriers were identified by population screening and randomly assigned to a screening group (group A, 3712 men), and controls (group B, 1869 men). Screening was planned to be six monthly alpha-fetoprotein (AFP) assays, with follow-up of subjects having an abnormal (>/=20 micrograms/l) test. All subjects were followed up for liver cancer and/or death until 31 December 1995. RESULTS: The overall sensitivity and specificity of the programme was 55.3% and 86.5%, respectively; in subjects who complied with all scheduled screening tests, the values were 80.0% and 80.9%. Three hundred and seventy-four primary liver cancer (PLC) cases were diagnosed. The percentage of cases in stage I was significantly higher in group A (29.6%) than in group B (6.0%). The one-, three-, and five-year relative survival rates were 23.7%, 7.0%, and 4.0% in group A, and 9.7%, 4.0%, and 4.1% in group B respectively, with no difference in five-year survival between the groups. The mortality rate in the screened group (1138 per 100,000 person-years) was not significantly different from that in the controls (1114 per 100,000). A Poisson regression model showed that the probability of death (rate ratio) in the screening group was 0.83 (95% CI 0.68-1.03) relative to the control group. CONCLUSIONS: Screening with AFP resulted in earlier diagnosis of liver cancer, but the gain in lead time did not result in any overall reduction in mortality, because therapy for the patients found by screening was ineffective. Further studies using improved methods of screening, diagnosis and treatment are indicated.

Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: results of urine genotoxicity assays as related to smoking habits.

A Phase II chemoprevention trial was carried out in Qidong, Jiangsu Province, People's Republic of China. The recruited subjects, all of whom were positive for serum aflatoxin-albumin adducts, were divided into three treatment arms: placebo; oltipraz ([5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione]) given daily at 125 mg p.o.; and oltipraz given once per week at 500 mg p.o. Besides biomarkers related to aflatoxin B(1) exposure, the genotoxicity of blind-coded urine XAD-2 concentrates was evaluated in 201 subjects on the fifth and seventh week of intervention. Genotoxicity was assessed both in the Ames reversion test in strain YG1024 of Salmonella typhimurium, in the presence of an exogenous metabolic system (S9 mix), with or without beta-glucuronidase, and in a DNA repair test in Escherichia coli. Heating of concentrated urine samples or of cigarette smoke condensates was discovered to result in a significant enhancement of their mutagenicity. It was also found that the mutagenicity of condensates from the most extensively used brands of cigarettes in Qidong was much lower than that of Western cigarette brands. Urine mutagenicity was unrelated to treatment with oltipraz, intervention time, gender, and supplement of S9 mix with beta-glucuronidase. Mutagenicity was significantly but variably higher in cigarette smokers than in nonsmokers, which suggests that the urinary excretion of mutagens in the examined population was not exclusively attributable to smoking. Nevertheless, within smokers (28% of the recruited subjects; 67% of all males), the mutagenic potency was significantly correlated with the self-reported number of cigarettes smoked per day and, even more sharply, with the cotinine concentrations in urines. In conclusion, this study demonstrated the validity of urine mutagenicity assays as a biomarker of tobacco smoke exposure that can be investigated on a relatively large scale in chemoprevention trials and provided evidence that oltipraz treatment had no influence on this parameter in the examined population.

Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People's Republic of China.

BACKGROUND: Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins, which require metabolic activation to become carcinogenic. In a randomized, placebo-controlled, double-blind phase IIa chemoprevention trial, we tested oltipraz, an antischistosomal drug that has been shown to be a potent and effective inhibitor of aflatoxin-induced hepatocarcinogenesis in animal models. METHODS: In 1995, 234 adults from Qidong were enrolled. Healthy eligible individuals were randomly assigned to receive by mouth 125 mg oltipraz daily, 500 mg oltipraz weekly, or a placebo. Sequential immunoaffinity chromatography and liquid chromatography coupled to mass spectrometry or to fluorescence detection were used to identify and quantify phase 1 and phase 2 metabolites of aflatoxin B1 in the urine of study participants. Reported P values are two-sided. RESULTS: One month of weekly administration of 500 mg oltipraz led to a 51% decrease in median levels of the phase 1 metabolite aflatoxin M1 excreted in urine compared with administration of a placebo (P = .030), but it had no effect on levels of a phase 2 metabolite, aflatoxin-mercapturic acid (P = .871). By contrast, daily intervention with 125 mg oltipraz led to a 2.6-fold increase in median aflatoxin-mercapturic acid excretion (P = .017) but had no effect on excreted aflatoxin M1 levels (P = .682). CONCLUSIONS: Intermittent, high-dose oltipraz inhibited phase 1 activation of aflatoxins, and sustained low-dose oltipraz increased phase 2 conjugation of aflatoxin, yielding higher levels of aflatoxin-mercapturic acid. While both mechanisms can contribute to protection, this study highlights the feasibility of inducing phase 2 enzymes as a chemopreventive strategy in humans.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers.

In 1995, 234 adults from Qidong, People's Republic of China, were enrolled and followed in a Phase IIa 4-methyl-5-(N-2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz) chemoprevention trial. Residents of this area are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods. The intervention was a randomized, placebo-controlled, double-blind study. Elements of the study design and clinical outcomes have been recently published (Jacobson et al, Cancer Epidemiol. Biomark. Prev., 6: 257-265, 1997). The primary objective was to conduct a preliminary assessment of the ability of oltipraz to modulate levels of a validated biomarker of aflatoxin exposure and of the risk of hepatocellular carcinoma by determining levels of aflatoxin-albumin adducts in sera. Healthy eligible individuals were randomized into three arms to receive p.o. 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo for 8 weeks. There were no consistent changes in biomarker levels in the placebo arm over the 16-week observation period, nor was any apparent effect observed in the arm receiving 125 mg of oltipraz each day. However, individuals receiving 500 mg of oltipraz once a week for 8 weeks showed a triphasic response to oltipraz. No effect was observed during the 1st month of the intervention, whereas a significant (P = 0.001) diminution in adduct levels was observed during the 2nd month of active intervention and during the lst month of follow-up. A partial rebound in adduct levels toward baseline values was observed during the 2nd month postintervention. Linear regression models up to week 13 confirmed a significant (P = 0.008) weekly decline of biomarker levels in the group receiving 500 mg of oltipraz once a week. However, despite these effects relative to baseline values within the 500-mg weekly arm, there were no statistically significant differences in biomarker trajectories between treatment arms. The genotype for glutathione S-transferase M1, an oltipraz-inducible isoform involved in the detoxification of aflatoxin B1, did not appear to affect either baseline levels or rates of decline in the biomarker. A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: study design and clinical outcomes.

In 1995, 234 adults from Qidong, Jiangsu Province, People's Republic of China, where hepatocellular carcinoma is the leading cause of cancer deaths and exposure to dietary aflatoxins is widespread, were enrolled and followed in a Phase II chemoprevention trial. The goals of the study were to define a dose and schedule of oltipraz for reducing levels of validated aflatoxin biomarkers and to characterize dose-limiting toxicities. Healthy eligible individuals, including those infected with hepatitis B virus, were randomized to receive either 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor toxicities and evaluate biomarkers over the 8-week intervention period and subsequent 8-week follow-up period. Unique trial aspects included a synchronous follow-up schedule, daily observed administration of all medications, timely international data transference, and use of biomarkers as outcomes. One hundred thirty-two participants took their medications without interruptions, approximately 77% contributed all nine urine samples, and 78% contributed all seven blood samples. Fifty-one participants (21.8%) reported clinical adverse events. An extremity syndrome, developing soon after the start of treatment, was the only event that occurred more frequently (P = 0.002) among the active groups (18.4 and 14.1% of the daily 125 and weekly 500 mg arms, respectively) compared with placebo (2.5%). The oltipraz arms did not differ in symptom type or severity, and there were no indications of exacerbated drug intolerance among the few participants infected with hepatitis B virus. The good compliance with an intense follow-up schedule shows that chemoprevention trials with biomarker end points may be conducted in such populations.

Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China.

Oltipraz has been used clinically in many regions of the world as an antischistosomal agent and is an effective inhibitor of aflatoxin hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-blind intervention was conducted in residents of Qidong, People's Republic of China, who are at high risk for exposure to aflatoxin and development of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the participants, and to further characterize dose-limiting side effects. Two hundred thirty-four healthy eligible individuals, including those infected with HBV, were randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potential toxicities and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow-up periods. Overall, compliance in the intervention was excellent; approximately 85% of the participants completed the study. Objective evaluation of adverse events was greatly facilitated by inclusion of a placebo arm in the study design. A syndrome involving numbness, tingling, and pain in the fingertips was the only event that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved with non-steroidal antiinflammatory agents. A more complete understanding of the chemopreventive utility of oltipraz awaits completion of an assessment of the efficacy of oltipraz in modulating levels of aflatoxin biomarkers.

Reproducibility of an esophageal biopsy sampling procedure in a high-incidence area for esophageal cancer in northern China.

The objective of this study was to evaluate the reproducibility of the biopsy sampling procedure in research on esophageal lesions. Biopsies were taken from the middle and lower thirds of the esophagus, one from each site, from 25 subjects in a high-incidence area for esophageal cancer in Xinye County of Henan Province, China. The biopsy sampling procedure was repeated on the same subjects 10 days later. When the biopsies were analyzed together and those with worse pathologies were used for diagnosis, 52% of the subjects had the same grade of lesions in the second biopsy examination, 32% had lower-grade lesions, and 16% had higher-grade lesions.