Oxidative damage, pro-inflammatory cytokines, TGF-α and c-myc in chronic HCV-related hepatitis and cirrhosis

AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-alpha and c-myc. METHODS: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-alpha, IL-1beta, TGF-alpha and c-myc in liver specimens was detected by semi-quantitative comparative RT-PCR. RESULTS: TNF-alpha levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1beta was higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-alpha and staging (P=0.05) and between IL-1beta levels and grading (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-alpha expression and HCV genotype (P=0.02). CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-alpha levels. As HCV-related liver damage progresses, TNF-alpha levels drop while IL-1beta and c-myc levels increase, which may be relevant to liver carcinogenesis.     

Effects of Zhaoyangwan on chronic hepatitis B and posthepatic cirrhosis

AIM:To study the therapeutic effects of zhaoyangwan(ZYW) on chronic hepatitis B and hepatic cirrhosis and theanti-virus,anti-fibrosis and immunoregulatory mechanismsof ZYW.METHODS:Fifty cases of chronic hepatitis B and posthepaticcirrhosis with positive serum HBsAg,HBeAg,anti-Hbc andHBV-DNA were divided randomly and single-blindly intothe treatment group (treated with ZYW) and the controlgroup (treated with interferon).After 3 month treatment,the effects of the treatment group and the control groupwere evaluated.RESULTS:The serum ALT normalization was 83.3%(30/36)in the treatment group and 85.7%(12/14) in the controlgroup,with no significant difference (X~2=0.043,P>0.05).After the course,the negative expression rates of the serumHBV-DNA and HBeAg were 44.4%(16/36) and 50%(18/36)in the treatment group,and 50%(7/14) and 50%(7/14) inthe control group,respectively,with no significant difference(X~2=0.125,X~2=0.00,both P>0.05).Negative HBsAg andpositive HBsAb appeared in 4 cases of the treatment groupand 1 case of the control group.Serum anti-HBc turnednegative in 6 cases of the treatment group and 1 case ofthe control group,respectively.After the ZYW treatment,serum CD_3~ ,CD_4~ ,CD_8~ ,CD_4~ /CD_8~ and NK cell activationwere significantly increased.Only serum CD_3~ and NK cellactivation were significantly increased in the control groupwith a significant difference between the two groups.Theserum C_4,C_(1q),C_3,B and C_9 were significantly increased inthe treatment group.In the control group only the serumwas increased.The concentration of serum interferon hadno change after treatment with ZYW,while it was significantlyincreased in the control group after treatment with interferon.The ultrastructure of the liver restored,which helped effectivelyto reduce the degeneration and necrosis of hepatic cells,infiltration of inflammatory cells and hepatic cirrhosis.CONCLUSION:ZYW is a pure Chinese herbal medicine.Itcan exert potent therapeutic effects on chronic hepatitis Band posthepatic cirrhosis.ZYW has similar therapeutic effectsto those of interferon.It is cheap and easily administeredwith no obvious side-effects.It can be widely used in clinicalpractice.     

Danshao Huaxian capsule in treatment of decompensated cirrhosis resulting from chronic hepatitis B

BACKGROUND: The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are ourweight serious sideeffects and the risk of fatal exacerbation of disease. Danshao Huaxian capsule rapidly reduces hepatitis B virus(HBV)-DNA in serum to undetectable levels. METHODS: A total of 35 patients with chronic hepatitis B and decompensated cirrhosis were treated with Danshao Huaxian 1.2g. po. tid daily. Before the treatment, HBVDNA in serum was positive in all patients. Ten patients had Child-Pugh class B and 25, class C hepatitis B. Seven patients underwent liver transplantation within 6 months of initial treatment. Of the 10 patients of class B, 5 died within 6 months, and the other 5 did not complete the treatment for some reasons; the 25 patients of class C were treated for at least 6 months (mean =19 months). RESULTS: In most of the 25 patients, liver function was improved slowly but markedly after 9 months of treatment, showing a decreased level of serum bilirubin from 67±13 to 30±4μmol/L (P<0.05, baseline vs.6 months), an increased level of serum albumin from 27±1 to 34±1 g/L(P<0.05) and a decreased level of Child-Pugh score from 10.3±0.4 to 7.5+0.5 (P<0.05). Three patients developed resistance to Danshao Huaxian because of a mutation in the YMDD motif, but liver function was not deteriorated. Inhibition of viral replication with Danshao Huaxian resulted in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term results remain uncertain. CONCLUSION: Danshao Huaxian capsule is effective in inhibiting viral DNA replication in patients with decompensated cirrhosis and making clinical improvement.     

What is the real prevalence of the D virus infection in chronic hepatitis and liver cirrhosis in Romania?

Virus D hepatitis continues to represent a public health problem in the south-eastern European countries, but the spread of the D virus infection in Romania is not completely elucidated. The paper proposes to assess the prevalence of the hepatitis D virus infection in patients with HBsAg-positive chronic hepatitis and liver cirrhosis in Romania. A number of 219 patients with chronic hepatitis and 168 with liver cirrhosis, all testing positive for HBsAg were studied. Viral markers were determined by immunoenzymatic methods. In HBsAg-positive chronic hepatitis the prevalence of the D virus was 37.9 % and in liver cirrhosis 51.19%. The great majority of the cases infected with hepatitis B virus were HBeAg-negative. These findings situate Romania among countries with a high prevalence of the hepatitis D virus infection, but which is decreasing as compared to the data communicated by previous reports.     

Is laparoscopy an advantage in the diagnosis of cirrhosis in chronic hepatitis C virus infection？

AIM: To evaluate the potential of laparoscopy in the diagnosis of cirrhosis and outcome of interferon treatment in HCV-infected patients. METHODS: In this retrospective study, diagnostic laparoscopy with laparoscopic liver biopsy was performed in 72 consecutive patients with chronic HCV infection. The presence or absence of cirrhosis was analyzed macroscopically by laparoscopy and microscopically by liver biopsy specimens. Clinical and laboratory data and outcome of interferon-alfa treatment were compared between cirrhotic and noncirrhotic patients. RESULTS: Laparoscopically, cirrhosis was seen in 29.2 % (21/72) and non-cirrhosis in 70.8 % (51/72) of patients. Cirrhotic patients were significantly older with a significant longer duration of HCV infection than noncirrhotic patients. Laboratory parameters (AST, y-GT, y-globulin fraction) were measured significantly higher as well as significantly lower (prothrombin index, platelet count) in cirrhotic patients than in non-cirrhotic patients. Histologically, cirrhosis was confirmed in 11.1 % (8/72) and non cirrhosis in 88.9 % (64/72). Patients with macroscopically confirmed cirrhosis (n=21) showed histologically cirrhosis in 38.1 % (8/21) and histologically non-cirrhosis in 61.9 % (13/21). In contrast, patients with macroscopically non-cirrhosis (n=51) showed histologically non cirrhosis in all cases (51/51). Thirty-nine of 72 patients were treated with interferon-alfa, resulting in 35.9 % (14/39) patients with sustained response and 64.1 % (25/39) with non response. Non-responders showed significantly more macroscopically cirrhosis than sustained responders. In contrast, there were no significant histological differences between non-responders and sustained responders. CONCLUSION: Diagnostic laparoscopy is more accurate than liver biopsy in recognizing cirrhosis in patients with chronic HCV infection.Liver biopsy is the best way to assess inflammatory grade and fibrotic stage. The invasive marker for staging, prognosis and management, and treatment outcome of chronic HCV-infected patients need further research and clinical trials. Laparoscopy should be performed for recognition of cirrhosis if this parameter is found to be of prognostic and therapeutic relevance in patients with chronic HCV infection.     

Oxidative DNA damage and β-catenin expression in colorectal cancer evolution

Purpose

Oxidative DNA damage is one of the mechanisms associated to initial colorectal carcinogenesis, but how it interacts with β-catenin, an adherence protein related to cancer evolution, is not clear. This study investigates the relationship between oxidative DNA damage and β-catenin expression in normal mucosa and colon tumor tissue (adenoma and adenocarcinoma) in colorectal adenocarcinoma evolution.

Method

One hundred and 13 samples were studied. Hematoxylin–eosin determined histological grade. β-Catenin expression was analyzed by immunohistochemistry. The oxidative DNA damage was evaluated using comet assay technique. The coefficient for rejection of the nullity hypothesis was taken to 5 %. Kruskal–Wallis, Spearman test, and partial correlation were used to analyze the data.

Results

There was oxidative DNA damage increase in colorectal cancer evolution (p?<?0.01). Histological grade was correlated with oxidative DNA damage (p?<?0.01). There were differences in β-catenin expression among normal, adenoma, and adenocarcinoma tissue with progressive increase of β-catenin expression (p?<?0.00). Histological grade was correlated to β-catenin expression (p?<?0.00). There was a relationship (p?<?0.00) between β-catenin and histological grade while controlling for the effect of oxidative DNA damage.

Conclusion

The findings of this study make it possible to establish a relationship between oxidative DNA damage and β-catenin expression in normal mucosa and colorectal tumor tissue. Additionally, they show a causal relationship between variations of β-catenin in different tissues analyzed while controlling for the effect of oxidative DNA damage.     

Effect of probiotics on pro-inflammatory cytokines and NF-��B activation in ulcerative colitis

AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients with mild to moderate UC were randomly classified into two groups:sulfasalazine group,who received sulfasalazine 2400 mg/d;and probiotic group,who received sulfasalazine 2400 mg/d with probiotic.The patients were investigated before and after 8 wk of treatment with probiotic(Lactobacillus delbr...     

TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells

Background  

Phosphatidylcholine (PC) is a major lipid of the gastrointestinal mucus layer. We recently showed that mucus from patients suffering from ulcerative colitis has low levels of PC. Clinical studies reveal that the therapeutic addition of PC to the colonic mucus using slow release preparations is beneficial. The positive role of PC in this disease is still unclear; however, we have recently shown that PC has an intrinsic anti-inflammatory property. It could be demonstrated that the exogenous application of PC inhibits membrane-dependent actin assembly and TNF-α-induced nuclear NF-κB activation. We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties.     

Study of pro-inflammatory (TNF-α, IL-1α, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: Correlations with clinical and laboratory parameters

Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory (TNF-, IL-1, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in pauciarticular and polyarticular juvenile chronic arthritis (JCA) patients during the active (n=22) and inactive (n=14) period in order to determine pathogenic mechanisms and correlations between cytokines and laboratory parameters showing disease activity. The erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG concentrations were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral blood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells (22.5%) were found to be significantly increased. In the active period of JCA, plasma TNF- and IL-6 concentrations were significantly elevated. Plasma IL-2 and IL-4 levels were not elevated and were found to be similar to those in the inactive phase and in healthy controls. SF IL-6, TNF- and IL-1 levels were extremely high in all the patients. SF IL-4 and IL-2 levels were all undetectable. There was a significant correlation between ESR values and plasma IL-6 levels and between serum CRP levels and plasma IL-6 and TNF- concentrations. In conclusion, increased local production of pro-inflammatory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production was not suggested to be primarily involved in the pathogenesis. In addition, not only CRP and ESR values, but also plasma IL-6 and TNF- concentrations may be used as markers of disease activity.     

Histological versus clinical cirrhosis in chronic hepatitis C: does race/ethnicity really matter?

Abstract  

Liver fibrosis progression in hepatitis C virus (HCV) infection has been in part associated with race/ethnicity. Little is known of the frequency of clinical cirrhosis in Asian patients in the US.     

Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis： Differences and similarities

AIM： To investigate the prevalence of the clinical pa- rameters of insulin resistance and diabetes in patients affected by chronic hepatitis C （CHC） or chronic hepa- titis B （CHB）. METHODS： We retrospectively evaluated 852 consec- utive patients （726 CHC and 126 CriB） who had under- gone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome （MS）, body mass index （BMI）, and apparent disease duration （ADD）. RESULTS： Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biop- sies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis （〉 30%） and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis 〉 30% in CHC, whereas only age and BMI were related to steatosis in CriB. CONCLUSION： These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.     

M4 and M9 antibodies in the overlap syndrome of primary biliary cirrhosis and chronic active hepatitis: epitopes or epiphenomena?

Before the identification of the major mitochondrial antigens of primary biliary cirrhosis as components of the 2-oxo-acid dehydrogenase enzyme family, mitochondrial autoantigens were believed to be extremely heterogeneous and were divided into nine subtypes termed M1 to M9. This classification was based on the data derived from the relatively nonspecific biochemical and immunological techniques that were available. After the cloning and definition of the major autoantigens, more than 95% of the sera of patients with primary biliary cirrhosis were found to react with components of the 2-oxo-dehydrogenase enzymes; these enzymes correspond to the old M2 classification. Two other "M" species, dubbed M4 and M9, have attracted significant attention because they have been postulated to be prognostic indicators and more recently have been tentatively identified respectively as sulfite oxidase (EC 1.8.3.1) and glycogen phosphorylase (EC 2.4.1.1). Indeed, patients with the "overlap syndrome" are reported to have antibodies to M4 and a poor prognosis, whereas patients with antibodies to M9 have a favorable prognosis. To address the significance and definition of M4 and M9, we performed in-depth studies of sera from 11 patients with the overlap syndrome, 75 patients with primary biliary cirrhosis, 19 chronic active hepatitis patients, 13 patients with primary sclerosing cholangitis, 10 patients with cholangiocarcinoma, 20 patients with systemic lupus erythematosus, 20 patients with alcoholic cirrhosis, 17 patients with scleroderma and 30 normal individuals, using techniques of ELISA, complement fixation, immunoblotting and enzyme inhibition. We report herein that we were unable to show any disease-specific reactivity toward the proposed M4 and M9 antigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response guided therapy in patients with chronic hepatitis C – Yesterday,today and tomorrow

The rapidity of viral disappearance on antiviral treatment of chronic hepatitis C with peginterferon/ribavirin correlates with the cure rate. The earlier the virus becomes undetectable, the higher are the response rates. This observation is the basis of response-guided therapy. Viral clearance within the first 4 weeks of treatment is called a rapid virologic response (RVR). The rate of RVR varies among various populations, with the highest one observed in Asian patients and the lowest in African-Americans. This can be partly explained by a polymorphism in the region of the 5IL28B gene. In patients infected with genotypes 1 and 4 with RVR treatment with peginterferon/ribavirin can be shortened to just 24 weeks (with SVR rates of >80%). In contrast, patients with a slow decline in viral load (>2 log drop after 12 weeks with still detectable virus) may benefit from treatment extension to 72 weeks. The virologic response criteria were modified for triple therapy (extended RVR; HCV-RNA undetectable: telaprevir week 4 and 12; boceprevir week 8 and 24). Patients with eRVR can be cured by an abbreviated treatment regime. Further modification and unification of response criteria are needed for the currently evaluated interferon-free treatment regimes.     

Expression of ICAM-1, HLA-DR, and CD80 on peripheral circulating CD_1αDCs induced in vivo by IFN-αin patients with chronic hepatitis B

AIM: To explore the effects of interferon-α(IFN-α) application on peripheral circulating CD1αdendritic cells (DCs) in patients with chronic hepatitis B, and the expression of HLA-DR, CD80, and ICAM-1 on CD1αDCs in order to explore the mechanism of immune modulation of IFN-α. METHODS: By flow cytometry technique, changes of CD1αDCs were monitored in 22 patients with chronic hepatitis B treated with IFN-αand in 16 such patients not treated with IFN-αwithin three months. Meanwhile, the expression of HLA-DR, CD80, and ICAM-1 on CD1αDCs was detected. RESULTS: In the group of IFN-αtreatment, the percentage of CD1αDCs in peripheral blood mono-nuclear cells was increased after three months of therapy. In patients who became negative for HBV-DNA after IFN-αtreatment, the increase of DCs was more prominent, while in control, these changes were not observed. Increased expression of HLA-DR, CD80, and ICAM-1 on CD1αDCs was also observed. CONCLUSION: CD1αDCs can be induced by IFN-αin vivo, and the immune related molecules such as HLA-DR, CD80, and ICAM-1 are up-regulated to some degree. This might be an important immune related mechanism of IFN-αtreatment for chronic hepatitis B.     

Efficacy and safety of lamivudine treatment for chronic hepatitis B in pregnancy

AIM:To evaluate the efficacy and safety of lamivudinetreatment of chronic hepatitis B disease in pregnancy.METHODS:The study group was comprised of 38 chronicHBV patients who were diagnosed pregnant duringIamivudine treatment and voluntary to continue the sametherapy.The control group was from documented patientdata in the literatures.We compared the followingparameters with those of a control group:anti-HBV efficacy,complications of pregnancy (abortion,preterm birth,neonatalasphyxia,fetal death,and congenital anomaly),incidenceof HBV-positive babies and developmental anomalies inpregnant women treated with Iamivudine.RESULTS:The blocking rate of lamivudine treatment wassignificantly higher than that of active vaccine immunizationfor babies with double-positive (HBsAg/HBeAg) mothers with30-30-10 μg doses of vaccine (74.07%) and with 30-20-10 μg(64.87%).The natural vertical HBV transmission from motherto infant of “double-positive”mothers was 100% (10/10).No pregnancy complication was noted during the observationperiod,but in the control group the incidences of pregnancycomplication were 16.67% (abortion),43.02%(preterm),15.62% (neonatal asphyxia),and 4.49% (fetal death),10.0% (congenital anomaly).No HBV-positive newborn wasdetected and no developmental anomaly was found in thestudy group.CONCLUSION:Lamivudine is helpful to prevent maternal-infant HBV transmission and may reduce the complicationsof HBV-infected pregnant patients.     

Early diagnosis of bacterial and fungal infection in chronic cholestatic hepatitis B

AIM:To investigate the early diagnostic methods of bacterialand fungal infection in patients with chronic cholestatichepatitis B.METHODS:One hundred and one adult in-patients withchronic hepatitis B were studied and divided into 3 groups:direct bilirubin(DBil)/total bilirubin(TBil)≥0.5,withoutbacterial and fungal infection(group A,n=38);DBil/TBil<0.5,without bacterial and fungal infection(group B,n=23);DBil/TBil≥0.5,with bacterial or fungal infection(group C,n=40).The serum biochemical index and pulse rate wereanalyzed.RESULTS:Level of TBil,DBil,alkaline phosphatase(ALP)and DBil/ALP in group A increased compared with that ingroup B.The level of ALP in group C decreased comparedwith that in group A,whereas the level of TBil,DBil andDBil/ALP increased(ALP:156±43,199±68,respectively,P<0.05;TBil:370±227,220±206,respectively,P<0.01;DBil:214±143,146±136,respectively,P相似文献