氯乙烯、三硝基甲苯中毒肝病与病毒肝炎鉴别诊断

本文对22名病毒肝炎、21名中毒肝病患者及61名健康人进行了血清胆甘氨酸(CG)和白细胞介素-1(IL-1)实验研究。发现病毒肝炎患者血清CG和IL-1平均含量分别为545.9μg/dl和408.8pg/ml;中毒肝病组分别为88.9μg/dl和34.2pg/ml;健康组上述两项指标均低于正常值上限(CG为58μg/dl,IL-l 47pg/ml)。结果表明CG与IL-l结合使用可望为诊断与鉴别VC和TNT中毒肝病与病毒肝炎提供新的指标,具有较大实用价值。

三种疑难肝病的藏医治疗

藏医学对肝病中的的隐性肝病、类中毒肝病、肝血下注症等疑难病种的诊治积累了丰富而颇有疗效的临床经验,清热、消杀、下泻、活血、养肝的治则及放血疗法开辟了蹊径,弥补了其他医药对该病治疗的不足。

染发剂致慢性中毒性肝病1例

1病例资料患者,王某,男,61岁,因发现肝功能异常2年入院,患者2年前查肝功示丙氨酸氨基转移酶、天冬氨酸氨基转移酶升高(具体不详),偶有乏力、牙龈出血,1个月前于我院内分泌科住院期间查肝功示丙氨酸转氨酶(ALT)85 U/L、天冬氨酸转氨酶(AST)43 U/L、γ-谷氨酰转肽酶(γ-GTT)330 U/L,腹部彩超示:脂肪肝、脾大,未特殊诊治,现患者为明确肝损害、脾大原因就诊于我科。既往:脾大伴血小板减少2年,病因未详,未系统诊治;2型糖尿病病史1个月,现规律应用甘精胰岛素(12 U/次,晚1次),口服利格列汀(5 mg/次,早1次)控制血糖。否认病毒性肝炎、结核病史,无烟酒嗜好。查体:血压130/76 mmHg,心率68次/min,呼吸13次/min,余未见明显阳性体征。

Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, P【0.001). The differences of the expressions were significant between the patients from each groups (alcoholic steatosis, alcoholic hepatitis and alcoholic cirrhosis) and the controls (1.168 +/- 0.852, 1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.808 +/- 0.276, P【0.050). No significant differences of TGF -beta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, P【0.050). No significant differences of TGF-beta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients.

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.

Hydroxycut hepatotoxicity:A case series and review of liver toxicity from herbal weight loss supplements

Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the setting of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements, and their individual components which have demon-strated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted.

Epidemiology of Hepatitis B and Associated Liver Diseases in China

Hepatitis B virus (HBV) infection has long been a critical public health challenge in China. National surveys revealed a prevalence of approximate 10% for chronic HBV infection in general population. HBV has been the leading cause of chronic hepatitis, cirrhosis, and liver cancers in Chinese population and a common pathogen of acute viral hepatitis. Meanwhile, the epidemic provided important opportunities to research the natural history, public health impact, and therapeutic and preventive interventions for HBV in China. In this review, we summarized the selected key epidemiological studies since 1970s regarding HBV infection and its associated liver diseases in China, and provided considerations for future research, prevention and treatment of HBV.

Imatinib-induced fatal acute liver failure

Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia (CML) in blast crisis, accelerated or chronic phase, and also for advanced gastrointestinal stromal tumors. Severe hepatic toxicity and three deaths from hepatic failure have been reported. We report the case of a 51-year-old woman who was admitted to our institution with severe acute hepatitis. She was diagnosed with CML and began treatment with imatinib mesylate at a dose of 400 mg/d. Five months after beginning treatment, she developed severe hepatitis associated with coagulopathy, and was admitted to our institution. She had been consuming acetaminophen 500-1000 mg/d after the onset of symptoms. She had a progressive increase in bilirubin level and a marked decrease of clotting factor Ⅴ. Five days after admission, grade Ⅱ encephalopathy developed and she was referred for liver transplantation. Her clinical condition progressively deteriorated, and 48 h after being referred for transplantation she suffered a cardiac arrest and died. This report adds concern about the possibility of imatinib-mesylate-induced hepatotoxicity and liver failure, particularly in the case of concomitant use with acetaminophen. Liver function tests should be carefully monitored during treatment and, with the appearance of any elevation of liver function tests, treatment should be discontinued.

Transient and etiology-related transcription regulation in cirrhosis prior to hepatocellular carcinoma occurrence

AIM： To search for transcription dysregulation that could （1） differentiate hepatocellular carcinoma （HCC）-free from HCC-related cirrhosis （2） differentiate HCC-free cirrhosis related to HCV from that related to alcohol intake. METHODS： Using microarray analysis, we compared transcript levels in HCC-free cirrhosis （alcoholism： 7; hepatitis C： 7）, HCC-associated cirrhosis （alcoholism： 10; hepatitis C： 10） and eight control livers. The identified transcripts were validated by qRT-PCR in an independent cohort of 45 samples （20 HCC-free cirrhosis; 15 HCC-associated cirrhosis and 10 control livers）. We also confirmed our results by immunohistochemistry.RESULTS： In HCC-free livers, we identified 70transcripts which differentiated between alcoholicrelated-cirrhosis, HCV-related cirrhosis and control livers. They mainly corresponded to down-regulation. Dysregulation of Signal Transduction and Activator of Transcription-3 （STAT-3） was found along with related changes in STAT-3 targets which occurred in an etiology-dependent fashion in HCC-free cirrhosis. In contrast, in HCC, such transcription dysregulations were not observed. CONCLUSION： We report that transcriptional dysregulations exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC onset and may be appear like markers from cirrhosis to HCC transition.

Mutations in hepatitis B virus core regions correlate with hepatocellular injury in Chinese patients with chronic hepatitis B

AIM: To elucidate the relationship between the frequency of core mutations and the clinical activity of hepatitis B virus (HBV)-related liver disease and to characterize the amino acid changes in the core region of HBV.METHODS: We studied 17 Chinese patients with chronic hepatitis B according to their clinical courses and patterns of the entire core region of HBV.RESULTS: Amino acid changes often appeared in the HBV core region of the HBV gene in patients with high values of alanine aminotransferase (ALT) or with the seroconversion from HbeAg to anti-HBe. The HBV core region with amino acid changes had high frequency sites that corresponded to HLA Ⅰ/Ⅱ restricted recognition epitopes reported by some investigators.CONCLUSION: The core amino acid changes of this study occur due to influence of host immune system. The presence of mutations in the HBV core region seems to be important for predicting the clinical activity of hepatitis B in Chinese patients.

Antiviral effect of Chinese medicine jiaweisinisan in hepatitis B virus transgenic mice

AIM： To study the antiviral effect of Chinese medicine jiaweisinisan （JWSNS） on hepatitis B virus （HBV） infection in transgenic mice （TGM）. METHODS： Twenty two 6-8 wk old HBV TGM in the third generation were divided into TGM control group and TGM treated group randomly. The normal control group included ten normal BC 57L/6 mice at the same age. The mice in treated group were administrated with JWSNS at the concentration of 4 g/mL and the dosage of 50 g/kg per d for 30 d, while the mice in TGM control group and normal control group were administrated with normal saline at the same dosage and the same time. Polymerase chain reaction （PCR） was used to assess the contents of HBV DNA in serum of HBV TGM before and after treatments, whereas blot hybridization was utilized to measure the contents of HBV DNA in the liver of both HBV TGM and normal BC 57L/6 mice. RESULTS： The levels of serum HBV DNA in TGM treated group were remarkably decreased after the treatment of JWSNS （7.662±0.78 vs 5.22±3.14, P〈0.05）, while there was no obvious change after administration of normal saline in TGM control group （7.125±4.26 vs 8.932 ± 5.12, P〉 0.05）. The OD values of HBV DNA in the livers of the mice in TGM treated group were significantly lower than those of TGM control group （0.274±0.096 vs 0.432 ± 0.119, P 〈 0.01）. CONCLUSION： JWSNS exerts suppressive effects on HBV DNA in the serum and liver of TGM.

Role of nuclear receptor CAR in carbon tetrachloride-induced hepatotoxicity

AIM： To investigate the precise roles of CAR in CCI4- induced acute hepatotoxicity. METHODS： To prepare an acute liver injury model, CCI4 was intraperitoneally injected in CAR＋/＋ and CAR-/- mice. RESULTS： Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR-/- mice compared to CAR＋/＋ mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR-/- mice compared with CAR＋/＋ mice. On the other hand, androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR＋/＋ but not in CAR./. mice. Thus, CAR activation caused CCl4 hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity.There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR＋/＋ and CAR./. mice. However, the expression of other CCI4-metabolizing enzymes, such as CYP2B10 and 3All, was induced by PB in CAR＋/＋ but not in CAR-/- mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and 3All in the presence of activator or inhibitor. CONCLUSION： The nuclear receptor CAR modulates CCl4- induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drug- drug interaction even though such drugs themselves are not hepatotoxic.

Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

AIM： To test the psychometric properties of a Chinese [（Hong Kong） HK] translation of the chronic liver disease questionnaire （CLDQ）. METHODS： A Chinese （HK） translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B （CriB） patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese （HK） SF-36 Health Survey Version 2 （SF-36v2）. RESULTS： Scaling success was ≥ 80% for all but three items. A new factor assessing sleep was found and items of two （Fatigue and Systemic Symptoms） subscales tended to load on the same factor. Internal consistency and test-retest reliabilities ranged from 0.58-0.90 for different subscales. Construct validity was confirmed by the expected correlations between the SF-36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly lower in complicated compared with uncomplicated CHB, supporting sensitivity in detecting differences between groups.CONCLUSION： The Chinese （HK） CLDQ is valid, reliable and sensitive for patients with CHB. Some modifications to the scaling structure might further improve its psychometric properties,

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.

Acute hepatitis B or exacerbation of chronic hepatitis B-that is the question

Hepatitis B virus (HBV) infection constitutes a serious global health problem. In countries with intermediate or high endemicity for HBV, exacerbations of chronic hepatitis B may be the first presentation of HBV infection. Some of these patients may be diagnosed mistakenly as having acute hepatitis B. Accurate diagnosis in these cases is very important for deciding whether to start treatment or not, because acute hepatitis B does not require therapy, while exacerbation of chronic hepatitis may benefit from it. Clinical and routine laboratory findings cannot help distinguishing between these two conditions. Therefore, several assays have been proposed for this purpose during the last few years. The presence of high levels of anti-HBe antibodies, HBsAg and HBV DNA are typical of chronic disease, whereas high titers of IgM anti-HBc, together with their high avidity index, characterize acute HBV infection. Starting from the description of a patient with acute hepatitis B-who recently came to our observation-we critically review the currently available assays that may help distinguishing between the different conditions and lead to the optimal management of each patient.

二甲基甲酰胺致职业性慢性中毒性肝病1例分析

目的分析1例二甲基甲酰胺致职业性慢性中毒性肝病病例的诊疗经过及现场调查结果,为制定监管对策提供参考。方法收集、分析病例资料并开展现场卫生学调查。结果根据职业接触史、发病诊疗经过和病程,结合现场卫生学调查结果综合分析,患者诊断为职业性慢性中度中毒性肝病。结论长期接触二甲基甲酰胺可引起慢性中毒性肝病。用人单位应提高职业病防治主体责任意识,增强工人自我保护意识;监管部门应加大监管力度,严查违法行为,以保障劳动者健康权益。

Risk factors for primary liver carcinoma in Chinese population

AIM： To evaluate the risk factors for primary liver carcinoma （PLC） in Chinese population.METHODS： Chinese Biomedical Literature Database, China Hospital Knowledge Database and MEDLINE were searched. All the related literatures were screened, and the risk factors for PLC in Chinese population were studied. Heterogeneity was evaluated by odds ratio （OR） q test. Combined OR and its 95% confidence interval （95%CI）were calculated, the association between the investigated risk factors and PLC was determined. Validity and bias of the findings were evaluated by sensitivity analysis and funnel plot analysis respectively.RESULTS： Fifty-five of one hundred and ninety identified studies were accepted according to the inclusive criteria. Ten factors related to PLC were demonstrated by sensitive analysis and funnel plot analysis. They were cirrhosis （OR = 11.97, P= 0.000）, HBV infection （OR = 11.34, P= 0.000）,HCV infection （OR = 4.28, P = 0.000）, family history of liver cancer （OR = 3.49, P = 0.000）, unstable emotion （OR = 2.20, P = 0.000）, depressed characters （OR = 3.07,P = 0.000）, aflatoxin （OR = 1.80, P = 0.000）, alcoholic （OR = 1.88, P = 0.000）, intake of musty food （OR =1.87,P = 0.000） and drinking contaminated water from pond （OR = 1.77, P = 0.003）.CONCLUSION： The main risk factors for PLC in China are liver diseases, family history of liver carcinoma, poor psychic status, aflatoxin, and some unhealthy behaviors.

A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus

AIM： To determine the therapeutic effect of lamivu- dine in late pregnancy for the interruption of motherto-child transmission （MTCT） of hepatitis B virus （HBV）. METHODS： Studies were identified by searching available databases up to January 2011. Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials （RCTs） with lamivudine treatment in late pregnancy, and newborns or infants whose serum hepatitis B surface antigen （HBsAg）, hepatitis B e antigen （HBeAg） or HBV DNA had been documented. The relative risks （RRs） for inerruption of MTCT as indicated by HBsAg, HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval （CI） to estimate the efficacy of lamivudine treatment. RESULTS： Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis. The overall RR was 0.43 （95% CI, 0.25-0.76; 8 RCTs; Phet- erogeneity= 0.04） and 0.33 （95% CI, 0.23-0.47; 6 RCTs; Pheterogeneity = 0.93） indicated by newborn HBsAg or HBV DNA. The RR was 0.33 （95% CI, 0.21-0.50; 6 RCTs; Pheterogeneity = 0.46） and 0.32 （95% CI, 0.20-0.50; 4 RCTs; Pheterogeneity = 0.33） indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth. The RR （lamivudine vs hepatitis B immunoglobulin） was 0.27 （95% CI, 0.16-0.46; 5 RCTs; Pheterogeneity = 0.94） and 0.24 （95% CI, 0.07-0.79; 3 RCTs; Pheterogeneity = 0.60） indicated by newborn HBsAg or HBV DNA, respectively. In the mothers with viral load 〈 106 copies/mL after lamivudine treatment, the efficacy （RR, 95% CI） was 0.33, 0.21-0.53 （5 RCTs; Pheterogeneity = 0.82） for the interruption of MTCT, however, this value was not significant if maternal viral load was 〉 106 copies/mL after lamivudine treatment （P = 0.45, 2 RCTs）, as indicated by newborn serum HBsAg. The RR （lamivudine initiated from 28 wk of gestation vs control） was 0.34 （95% CI, 0.22-0.52; 7 RCTs; Pheterogeneity = 0.92） and 0.33 （95% CI, 0.22-0.50; 5 RCTs; Pheterogeneity = 0.86） indicated by newborn HBsAg or HBV DNA. The incidence of adverse effects of lamivudine was not higher in the mothers than in controls （P = 0.97）. Only one study reported side effects of lamivudine in newborns. CONCLUSION： Lamivudine treatment in HBV carrier- mothers from 28 wk of gestation may interrupt MTCT of HBV efficiently. Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT. HBV MTCT might be interrupted efficiently if maternal viral load is reduced to 〈 106 copies/mL by lamivudine treatment.

Epidemiology and prevention of hepatitis B virus in China

Hepatitis B virus （HBV） infection is prevalent in China. Approximately 600 million people have ever been infected by HBV. About 130 million are HBV chronic carders and 30 million HB patients. Among them, 50% of HBV carriers are caused by carrier mothers to born infants. Around 300 000 people died of liver disease including liver cirrhosis and primary hepatocellular carcinoma each year and 50% of them died of primary hepatocellular carcinoma. HBV infection is not only the health problem but also becoming a social problem. HBV chronic carriers and patients have endured the great pressure from disease burden and social discrimination. According to the report of the national screening program of HBV released by the ministry of health in 2008, China has taken many effective measures to control the HBV infection, including vaccine immunization program, strengthening the management of blood sources and blood productions, prevention of nosocomial HBV infection, strengthening health education on HBV infection and safe injection techniques. The implementation of HB vaccine immunization program, which China officially introduced into the national immunization program since 1992, has dramatically reduced the incidence of HBV infection among infants and children. Integrated with other interventions, the rate of HBV infection decreased gradually. According to the survey of the national screening program of HBV in 2006, compared with the incidence of HBV in 1992, the incidence rate of HBsAg positive has decreased 26.36%, the number of children who have ever been infected by HBV decreased 80 million since 1992. However some problems are still existing. The solutions of low rate of vaccination in rural areas and migration population, lacking of practical measures on management of hepatitis B patients, the occurrence of health care acquired HBV infection, and low rate of vaccination among high risk groups have also been recommended.

Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic hepatitis C: A randomized controlled trial

AIM:Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon. However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose. We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia. METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated. RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59±1.10 g/dL) was significantly (P= 0.026) smaller than that in the control group (3.71±0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Thl/Th2 balance between the two groups. There was no specific adverse effect in NYT administration. CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.