中药复方制剂的抗炎药理学研究

目的探讨一种新纯中药复方制剂的抗炎作用。方法采用二甲苯致小鼠耳肿胀[1]、醋酸致小鼠腹腔毛细血管通透性增高[2]、小鼠棉球肉芽肿及角叉菜胶致大鼠足肿胀等模型[3],研究其抗炎作用。结果高、低两种浓度的中药复方制剂对于小鼠耳廓肿胀率,以及减少大鼠炎足前列腺素E2的渗出有极显著的降低作用(P<0.01);另低浓度制剂对小鼠腹腔毛细血管的通透性和肉芽组织增生中有显著的降低作用(P<0.05),高浓度制剂对该指标有极显著作用(P<0.01)。结论该复方制剂对动物急性或慢性炎症模型均有不同程度的抑制作用,极具开发、研究价值。

关于止痛膏的几项试验研究

目的 :检验止痛膏的安全性以及是否具有镇痛、消炎功效。方法 :多次皮肤刺激试验、皮肤变态反应试验、慢性抗炎试验、止痛试验。结果 :对皮肤无刺激性 ,亦无变态反应发生 ,在消炎和止痛两项试验中 ,试验组与对照组比较 ,差异有显著性。结论 :该止痛膏可以安全使用并具有一定功效。

Expression of Lewis^b blood group antigen in Helicobacter pylori does not interfere with bacterial adhesion property

AIM: The finding that some Helicobacterpyloristrains expressLewis b (Leb) blood group antigen casts a doubt on the roleof Leb of human gastric epithelium being a receptor for-H.pylori. The aim of this study was to determine if expressionof Leb in H. Pyloriinterferes with bacterial adhesion property.METHODS: Bacterial adhesion to immobilized Leb onmicrotitre plate was performed in 63-H. Pyloristrains obtainedfrom Singapore using in vitro adherence assay. Expression ofLewis blood group antigens was determined by ELISA assay.RESULTS: Among 63 H. Pyloristrains, 28 expressed Lebantigen. In vitro adhesion assay showed that 78.6 % (22/28) of Leb-positive and 74.3 % (26/35) of Leb-negative-H.pyloriisolates were positive for adhesion to immobilized Lebcoated on microtitre plate (P＝0.772). In addition, blockingof H. Pylori Leb by prior incubation with anti-Leb monoclonalantibody did not alter thebinding of the bacteria to solid-phase coated Leb.CONCLUSION: The present study suggests that expressionof Leb in H. Pyloridoes not interfere with the bacterialadhesion property. This result supports the notion that Lebpresent on human gastric epithelial cells is capable of beinga receptor for H.pylori.

Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.

Telbivudine:A new treatment for chronic hepatitis B

Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include： standard interferon- alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues, which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel, orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment. Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no dose- limiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.

Nutritional status in relation to lifestyle in patients with compensated viral cirrhosis

AIM:To assess the nourishment status and lifestyle of non-hospitalized patients with compensated cirrhosis by using noninvasive methods.METHODS:The subjects for this study consisted of 27 healthy volunteers,59 patients with chronic viral hepatitis,and 74 patients with viral cirrhosis,from urban areas.We assessed the biochemical blood tests,anthropometric parameters,diet,lifestyle and physical activity of the patients.A homeostasis model assessment-insulin resistance(HOMA-IR) value of ≥ 2.5 was considered to indicate insulin resistance.We measured height,weight,waist circumference,arm circumference,triceps skin-fold thickness,and handgrip strength,and calculated body mass index,arm muscle circumference(AMC),and arm muscle area(AMA).We interviewed the subjects about their dietary habits and lifestyle using health assessment computer software.We surveyed daily physical activity using a pedometer.Univariate and multivariate logistic regression modeling were used to identify the relevant factors for insulin resistance.RESULTS:The rate of patients with HOMA-IR ≥ 2.5(which was considered to indicate insulin resistance) was 14(35.9%) in the chronic hepatitis and 17(37.8%) in the cirrhotic patients.AMC(%)(control vs chronic hepatitis,111.9% ± 10.5% vs 104.9% ± 10.7%,P = 0.021;control vs cirrhosis,111.9% ± 10.5% vs 102.7% ± 10.8%,P = 0.001) and AMA(%)(control vs chronic hepatitis,128.2% ± 25.1% vs 112.2% ± 22.9%,P = 0.013;control vs cirrhosis,128.2% ± 25.1% vs 107.5% ± 22.5%,P = 0.001) in patients with chronic hepatitis and liver cirrhosis were significantly lower than in the control subjects.Handgrip strength(%) in the cirrhosis group was significantly lower than in the controls(control vs cirrhosis,92.1% ± 16.2% vs 66.9% ± 17.6%,P < 0.001).The results might reflect a decrease in muscle mass.The total nutrition intake and amounts of carbohydrates,protein and fat were not significantly different amongst the groups.Physical activity levels(kcal/d)(control vs cirrhosis,210 ± 113 kcal/d vs 125 ± 74 kcal/d,P = 0.001),number of steps(step/d)(control vs cirrhosis,8070 ±3027 step/d vs 5789 ± 3368 step/d,P = 0.011),and exercise(Ex)(Ex/wk)(control vs cirrhosis,12.4 ± 9.3 Ex/wk vs 7.0 ± 7.7 Ex/wk,P = 0.013) in the cirrhosis group was significantly lower than the control group.The results indicate that the physical activity level of the chronic hepatitis and cirrhosis groups were low.Univariate and multivariate logistic regression modeling suggested that Ex was associated with insulin resistance(odds ratio,6.809;95% CI,1.288-36.001;P = 0.024).The results seem to point towards decreased physical activity being a relevant factor for insulin resistance.CONCLUSION:Non-hospitalized cirrhotic patients may need to maintain an adequate dietary intake and receive lifestyle guidance to increase their physical activity levels.

Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis

Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.

Different natural courses of chronic hepatitis B with genotypes B and C after the fourth decade of life

MIM： To investigate the different impact of genotypes E and C on the development of liver cirrhosis （LC） among different age groups of patients with chronic hepatitis （CH-B）.METHODS： We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC.RESULTS： In patients 〈 30 years old, there were no significant predictors for development of LC. However, in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12 patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis （7 patients were positive for HBeAg）. In the genotype B group, 4 of 8 patients who developed LC were ≥50 years old at initial diagnosis and were HBeAg-negative.CONCLUSION： The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at 〈 30 years old. However, CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs.

YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines

AIM: To polymerase P region (YMDD) mutations of hepatitis B virus gene (HBV DNA) in patients with chronic hepatitis B (CHB) untreated with antiviral medicines and to explore its correlation with pre-c-zone mutations, HBV genotypes and HBV DNA level, and to observe its curative effect.METHODS: A total of 104 cases (38 cases in group of familial aggregation and 66 cases in group of non-familial aggregation) were randomly chosen from 226 patients with CHB who did not receive the treatment of lamivudine (LAM)and any other antivirus drugs within the last one year.Their serum YMDD mutations were detected by microcosmic nucleic acid and cross-nucleic acid quantitative determination,HBV genotypes by PCR-microcosmic nucleic acid crossELISA, HBV DNA quantitative determination and fluorescence ration PCR analysis, hepatitis B virus markers (HBVM) by ELISA. LAM was taken by 10 patients with YMDD mutations and its curative effect was observed.RESULTS: Twenty-eight cases (26.9%) had YMDD mutations, of them 11 cases (28.9%) were in familial aggregation group (38 cases) and 17 cases (25.8%) in nonfamilial aggregation group (66 cases) with no significant difference between the two groups. Twenty-seven point one percent (16/59) cases were positive for HBeAg YMDD mutations, and 26.7% (12/45) cases were negative for HBeAg and positive for anti-HBe. There was also no significant difference between the two groups. Different YMDD incidence rate existed in different HBV genotypes.HBV DNA level did not have a positive correlation with the incidence of YMDD mutations. LAM was effective for all patients with mutations.CONCLUSION: Wild mutant strains in HBV and their incidence rate have no significant difference between familial aggregation and non-familial aggregation. It may have no significant relationship between YMDD mutations and pre-c-zone mutations. HBV DNA level may not have a positive correlation with YMDD mutations. LAM is clinically effective for CHB patients with YMDD mutations.

JNKs,insulin resistance and inflammation:A possible link between NAFLD and coronary artery disease

The incidence of obesity has dramatically increased in recent years.Consequently,obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem.Therefore,the contribution of adipose tissue to metabolic homeostasis has become a focus of interest.In this review,we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease.We describe the common mechanisms(cJun aminoterminal kinases,endoplasmic reticulum stress,unfolded protein response,ceramide,lowgrade chronic inflammation)by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall.Presenting the molecular mechanism of lipid activation of proinflammatory pathways,we attempt to find a link between nonalcoholic fatty liver disease,metabolic syndrome and cardiovascular diseases.Describing the common mechanisms by which lipid derivatives,through modulation of macrophage function,promote plaque instability in the arterial wall,impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of proinflammatory pathways,the key roles played by the proliferatoractivated receptor and liver X receptorα,nuclear receptorslipid sensors that link lipid metabolism and inflammation,should be emphasized.Further studies are warranted of antiinflammatory drugs such as aspirin,antiinterleukin6 receptors,immunemodulators(calcineurin inhibitors),substances enhancing the expression of heat shock proteins(which protect cells from endoplasmic reticulum stressinduced apoptosis),and anticJun aminoterminal kinases in welldesigned trials to try to minimize the high impact of these illnesses,and the different expressions of the diseases,on the whole population.

Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B

AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.

Efficacy of low dose peginterferon alpha-2b with ribavirin on chronic hepatitis C

AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During the study period of Jan 2002 to Dec 2003, all patients diagnosed as chronic hepatitis C or HCV related compensated cirrhosis were treated with peginterferon alpha 2b 50 μg S/C weekly (body weight < 60 kg) or 80 μg S/C weekly (body weight > 60 kg) plus ribavirin 800 mg/d for 24 wk. RESULTS: Overall 28 patients, 14 patients in each group (based on body weight) were treated during the period. Out of 28 patients, 75% were genotype 3, 18% were genotype 2 and 7% were genotype 1. The mean dose of peginterferon alpha 2b was 0.91 μg/kg in group 1 and 1.23 μg/kg in group 2 respectively. The end of treatment and sustained virologic response rates were 82% and 78% respectively. Serious adverse effects were seen in 3.5% patients. CONCLUSION: Low dose peginterferon alpha 2b in combination with ribavirin for 24 wk is effective in HCV genotype 2 and 3 chronic hepatitis C patients.

Interferon-α response in chronic hepatitis B-transfected HepG2.2.15 cells is partially restored by lamivudine treatment

AIM：To characterize the IFN-response and its modulation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS： HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-α 2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes （ISGs）. In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS： Two genes （MxA, CigS） with completely abolished and 4 genes （IFITM1, -2, -3, and 6-16） with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes （IFITM1, 6-16）, the response to IFN-α could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Statl activation and ISGF3 formation after stimulation with IFN-α in HepG2.2.15 compared to HepG2 cells. CONCLUSION： These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expressionby reducing HBV gene expression and replication.

Replication of clinical hepatitis B virus isolate and its application for selecting antiviral agents for chronic hepatitis B patients

AIM: To establish a cell model harboring replicative clinical hepatitis B virus (HBV) isolates and evaluate its application in individualized selection of anti-HBV agents for chronic hepatitis B (CHB) patients. METHODS: The full-length HBV genomic DNA from 8 CHB patients was amplified by polymerase chain reaction (PCR). All the patients were treated with lamivudine for at least seven months and finally became resistant to lamivudine. The amplified HBV DNA fragments were inserted into pHY106 vectors by Sap Ⅰ?digestion. The recombinant plasmids containing 1.1 copies of HBV genome were transiently transfected into Huh7 cell line, and the levels of HBsAg, HBeAg and intercellular HBV replicative intermediates were determined by ELISA and Southern blot analysis, respectively, with or without lamivudine and adefovir treatment. The antiviral treatment with adefovir was administered to the patients and analyzed in parallel. RESULTS: A total of 25 independent HBV isolateswere obtained from the sera of 8 patients, each patient had at least two isolates. One isolate from each individual was selected and subcloned into pHY106 vector, including 5 isolates with YVDD mutation and 3 isolates with YIDD mutation. All recombinant plasmids harboring HBV isolates were transfected into Huh7 cells. The results indicated that HBV genome carried in HBV replicons of clinical HBV isolates could effectively replicate and express in Huh7 cells. Adefovir, but not lamivudine, inhibited HBV replication both in vitro and in vivo, and in vitro inhibition was dose-dependent. CONCLUSION: The novel method described herein enables individualized selection of anti-HBV agents in clinic and is useful in future studies of antiviral therapy for CHB.

Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

AIM:To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acuteon-chronic liver failure(HBV-ACLF).METHODS:Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed.Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS:A total of 190 patients were included in this study.The overall 1-year survival rate was 57.6%.Patients not treated with antiviral drugs had a significantly higher mortality[relative risk(RR)=0.609,P=0.014].The highest risk of death in patients with ACLF was associated with hepatorenal syndrome(HRS)(RR=2.084,P=0.026),while other significant factors were electrolyte disturbances(RR=2.062,P=0.010),and hepatic encephalopathy(HE)(RR=1.879,P<0.001).CONCLUSION:Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate.HRS,electrolyte disturbances,and HE also affect patient survival.

Oxidative stress and damage induced by abnormal free radical reactions and IgA nephropathy

Objective: To estimate the oxidative stress and oxidative damage induced by abnormal free radical reactions in IgA nephropathy (IgAN) patients' bodies. Methods: Seventy-two IgA N patients (IgANP) and 72 healthy adult volunteers (HAV) were enrolled in a random control study design, in which the levels of nitric oxide (NO) in plasma, lipoperoxide (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and β-carotene (β-CAR) in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric mothods. Results: Compared with the HAV group, the averages of NO in plasma, and LPO in plasma and in erythrocytes in the IgANP group were significantly increased (P＜0.0001), while those ofVC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the IgANP group were significantly decreased (P＜0.0001). Linear correlation analysis showed that with the increase of the values of NO, and LPO in plasma and in erythrocytes, and with the decrease of those ofVC, VE, β-CAR,SOD, CAT and GPX in the IgAN patients, the degree of histological damage of tubulointerstitial regions was increased gradually (P＜0.0001); and that with the prolongation of the duration of disease the values of NO, and LPO in plasma and erythrocytes were increased gradually, while those of VC, VE, β-CAR, SOD, CAT and GPX were decreased gradually (P＜0.005). The discriminatory correct rates of the above biochemical parameters reflecting oxidative damage of the IgAN patients were 73.8%-92.5%, and the correct rates for the HAV were 70.0%-91.3% when independent discriminant analysis was used; and the correct rate for the IgAN patients was increased to 98.8%, the correct rate for the HAV was increased to 100% when stepwise discriminant analysis was used. The above biochemical parameters' reliability coefficient (alpha) were used to estimate the oxidative damage of the IgAN patients as 0.8145, the standardized item alpha=0.9730, F=53273.5681, P＜0.0001. Conclusions: A series of free radical chain reactions caused serious pathological aggravation in the IgANP' bodies, thus resulting in oxidative damage in their bodies. In treating IgANP, therefore, it is necessary that suitable dose antioxidants should be supplemented to them so as to alleviate the oxidative damage in their bodies.

Checkmate to liver biopsy in chronic hepatitis C?

Liver biopsy (LB) has traditionally been considered the gold standard for pretreatment evaluation of liver fibrosis in patients with chronic hepatitis C (CHC). However, LB is an invasive procedure with several shortcomings (intra-and interobserver variability of histopathological interpretation, sampling errors, high cost) and the risk of rare but potentially life-threatening complications. In addition, LB is poorly accepted by patients and it is not suitable for repeated evaluation. Further-more, the prevalence of CHC makes LB unrealistic to be performed in all patients with this disease who are candidates for antiviral therapy. The above-mentioned drawbacks of LB have led to the development of non-invasive methods for the assessment of liver fibrosis. Several noninvasive methods, ranging from serum marker assays to advanced imaging techniques, have proved to be excellent tools for the evaluation of liver fibrosis in patients with CHC, whereas the value of LB as a gold standard for staging fibrosis prior to antiviral therapy has become questionable for clinicians. Despite significant resistance from those in favor of LB, noninvasive methods for pretreatment assessment of liver fibrosis in patients with CHC have become part of routine clinical practice. With protease inhibitors-based triple therapy already available and substantial improvement in sustained virological response, the time has come to move forward to noninvasiveness, with no risks for the patient and, thus, no need for LB in the assessment of liver fibrosis in the decision making for antiviral therapy in CHC.

Effect of lamivudinein in BeAg-positive chronic hepatitis B: Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level

AM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo. RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs2, P= NS; groups 1 vs 3, P= 0.002; groups 1 vs4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P - NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02; groups 1 vs 3, P= NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.

Elevated plasma levels of N-terminal pro-brain natriuretic peptide in patients with chronic hepatitis C during interferon-based antiviral therapy

AIM: To investigate plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), an established marker of cardiac function, in patients with chronic hepatitis C during interferon-based antiviral therapy. METHODS: Using a sandwich immunoassay, plasma levels of NT-proBNP were determined in 48 patients with chronic hepatitis C at baseline, wk 24 and 48 during antiviral therapy and at wk 72 during follow-up.RESULTS: Plasma NT-proBNP concentrations were significantly increased (P < 0.05) at wk 24, 48 and 72 compared to the baseline values. NT-proBNP concentrations at baseline and wk 24 were closely correlated (r = 0.8; P < 0.001). At wk 24, 7 (14.6%) patients had NT-proBNP concentrations above 200 ng/L compared to 1 (2%) patient at baseline (P = 0.059). Six of these 7 patients had been treated with high-dose IFN-α induction therapy. In multiple regression analysis, NT-proBNP was not related to other clinical parameters, biochemical parameters of liver disease or virus load and response to therapy.CONCLUSION: Elevated levels of NT-proBNP during and after interferon-based antiviral therapy of chronic hepatitis C may indicate the presence of cardiac dysfunction, which may contribute to the clinical symptoms observed in patients during therapy. Plasma levels of NT-proBNP may be used as a diagnostic tool and for guiding therapy in patients during interferon-based antiviral therapy.

Association of chronic viral hepatitis B with insulin resistance

AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P < 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P < 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P < 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P < 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P < 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P < 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P < 0.001),waist circumference(r =0.356,P < 0.001),percent body fat(r = 0.296,P < 0.001),systolic blood pressure(r = 0.202,P < 0.001),total cholesterol(r = 0.134,P < 0.001),triglycerides(r = 0.292,P < 0.001),cystatin C(r = 0.069,P < 0.001) and uric acid(r = 0.142,P < 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P < 0.001),waist circumference(r = 0-0.243,P < 0.001),percent body fat(r =-0.217,P < 0.001),systolic blood pressure(r =-0.132,P < 0.001),total cholesterol(r =-0.106,P < 0.001),triglycerides(r =-0.205,P < 0.001),cystatin C(r =-0.044,P < 0.001) and uric acid(r =-0.096,P < 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.