The difference of IL-28B polymorphisms between hepatitis C patients with and without cryoglobulinemia / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine whether patients infected with chronic hepatitis C (CHC) show a differential distribution profile of IL-28B polymorphisms according to the presence of concomitant cryoglobulinemia.</p><p><b>METHODS</b>Sixty-two consecutive CHC patients were enrolled in the study between December 2008 and December 2010. All patients received combination therapy of pegylated interferon alpha-2a (weekly, 180 g, subcutaneous injection) plus ribavirin (daily, 10to15 mg/kg body weight, oral) for 48 weeks, with individualized dosage adjustments according to the patient's clinical situation. Cryoglobulins were detected visibly by separation of cryoprecipitates in patient serum samples. Three IL-28B SNPs (rs8099917, rs12979860, and rs12980275) were detected by sequencing. Response to treatment was assessed by measuring serum levels of HCV RNA by quantitative PCR at baseline (prior to treatment initiation), during treatment (4 and 12 weeks after treatment initiation), end of therapy (48 weeks after treatment initiation), and post-treatment (24 weeks after end of therapy). The significance of between-group differences were assessed by the Chi-square and Fisher's exact tests.</p><p><b>RESULTS</b>Cryoglobulinemia was detected in 43.5% (27/62) of the CHC patients and showed a female bias (59.3% vs. males: 34.3%, P = 0.05). Compared to CHC patients without cryoglobulinemia, the CHC patients with cryoglobulinemia showed significantly higher levels of HCV RNA at baseline (5.64+/-1.20 vs. 6.37+/-0.67, P less than 0.05) but lower frequencies of the IL28B rs8099917 TT genotype (94.3% vs. 63.0%, P = 0.002), rs8099917 T allele (97.1% vs. 81.5%, P = 0.003), and rs12979860 C allele (94.3% vs. 83.3%, P = 0.048). CHC patients with cryoglobulinemia and having the rs8099917 TT, rs12979860 CC, or rs12980275 AA genotype achieved a higher rate of sustained virological response.</p><p><b>CONCLUSION</b>Cryoglobulinemia in CHC patients is associated with a differential distribution of IL-28B polymorphisms, and certain polymorphisms may be related to anti-viral treatment response.</p>

Cryoglobulinemia is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mixed cryoglobulinemia (MC) is one of the most common and severe symptoms in chronic hepatitis C patients. The aim of this study was to investigate whether mixed cryoglobulinemia is a factor associated with sustained virological response in chronic hepatitis C patients treated with combination therapy of pegylated interferon alpha-2a and ribavirin.</p><p><b>METHODS</b>This is a single-center study including 57 chronic hepatitis C patients who received combination treatments of pegylated interferon alfa-2a and ribavirin. Serum cryoglobulin was detected by cryoprecipitation prior to treatment. Serum hepatitis C virus (HCV) RNA levels were checked before treatment, during the fourth and 12th week of treatment, and during the 24th week after cessation of treatment. The genotype of HCV was determined at baseline. Logistic regression analysis was used to assess the factors associated with sustained virological response.</p><p><b>RESULTS</b>Twenty-five patients were with MC (43.9%). Twenty-four weeks after cessation of antiviral treatment, sustained virological response achievement in MC(+) patients was significantly lower than that in MC(-) patients (32.0% vs. 75.0%, P = 0.001). Univariate Logistic regression analysis and multivariate Logistic regression analysis found that only MC (odds ratio: 6.375; 95% CI: 1.998- 20.343, P = 0.002) was negatively associated with sustained virological response achievement.</p><p><b>CONCLUSION</b>MC is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients treated with pegylated interferon alpha-2a and ribavirin.</p>

Efficacy of pegylated interferon-alpha-2a plus ribavirin for patients aged at least 60 years with chronic hepatitis C / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In China, patients with hepatitis C virus (HCV)-associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of the combination therapy in the elderly patients.</p><p><b>METHODS</b>Sixty-eight chronic hepatitis C patients, who received the combination therapy, were classified into two age groups: elderly group ((3)60 years, n = 25) and non-elderly group (< 60 years, n = 43). Rapid virological response, complete early virological response, sustained virological response, relapse, non-response rate, and safety were compared between the elderly group and non-elderly group.</p><p><b>RESULTS</b>Overall sustained virological response was lower in the elderly group than non-elderly group (44% vs. 75%, P = 0.012, OR = 0.270, and 95%CI 0.095 - 0.768). Among patients with HCV genotype 1, sustained virological response was lower in the elderly group than non-elderly group (45% vs. 77%, P = 0.015, OR = 0.247, 95%CI 0.078 - 0.781). The proportions of dose reduction due to laboratory abnormalities were significantly higher in the elderly group than non-elderly group (60.0% vs. 32.6%, P = 0.027). Multiple binary Logistic regression analysis confirmed that patient age was an associated factor for sustained virological response.</p><p><b>CONCLUSION</b>Among patients with HCV genotype 1, the elderly patients had lower sustained virological response than non-elderly patients during pegylated interferon-alpha-2a plus ribavirin combination therapy.</p>

The effect of cryoglobulinemia on the antiviral therapy in patients with chronic hepatitis C / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the possible influence of cryoglobulinemia on the antiviral effect in chronic hepatitis C patients, who were treated with combination therapy of pegylated interferon alpha-2a and ribavirin.</p><p><b>METHODS</b>Forty consecutive patients with chronic hepatitis C (CHC) were enrolled in the study. They received pegylated interferon alfa-2a (40kD, 180mug/w) along with ribavirin. Baseline cryoglobulins were detected in the sera by cryoprecipitation. Hepatitis C virus (HCV) genotyping was performed and HCV viral load was detected at baseline, and at 4, 12 weeks during treatment, 24 weeks after cessation of treatment.</p><p><b>RESULTS</b>Eighteen (45.0%) patients infected with HCV were cryoglobulins positive at baseline. Mean serum HCV RNA level in cryoglobulins positive patients was higher than that in cryoglobulins negative patients (6.36+/-0.63 vs. 5.70+/-1.20, P = 0.032). The rapid virological response (RVR) rate was statically different between cryoglobulins positive patients and cryoglobulins negative ones (6/18, 33.3% vs. 15/22, 68.2%, P = 0.028). In contrast, no difference was found in early virological response (EVR) rate between the cryoglobulins positive patients and cryoglobulins negative ones (14/17, 82.4% vs. 18/21, 85.7%, P = 1.0). Sustained virological response (SVR) rate in cryoglobulins positive and cryoglobulins negative was different (0/3, 0 vs 6/6, 100%, P = 0.012). The rate of patients achieved RVR was different between the patients infected with HCV genotype 1 b of two groups (cryoglobulins positive: 2/13, 15.4% vs cryoglobulins negative 14/21; 66.7%, P = 0.005). However, the rate of EVR in patients infected HCV genotype 1 b was not statistically different (cryoglobulins positive: 9/12, 75.0% vs. cryoglobulins negative 17/20; 81.2%, P = 0.647).</p><p><b>CONCLUSION</b>The rates of RVR and SVR achievement in cryoglobulinemia positive CHC patients are lower than those in cryoglobulinemia negative CHC patients.</p>

Prevalence of abnormal glycometabolism in patients with chronic hepatitis C and related risk factors in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>An epidemiologic link between hepatitis C virus (HCV) and abnormal glycometabolism had been established. This study was designed to investigate the prevalence of type 2 diabetes mellitus and insulin resistance, and to explore the relation between insulin resistance and hepatitis C virus genotype, serum hepatitis C virus-RNA level in chronic hepatitis C (CHC) patients.</p><p><b>METHODS</b>Three hundred and fifty-nine consecutive patients (CHC, n = 296; chronic hepatitis B (CHB), n = 63) were evaluated. HCV genotyping was performed by restriction fragment method and serum hepatitis C virus-RNA quantified PCR for all CHC patients in the baseline serum. Fasting levels of insulin and glucose were measured in all patients and the homeostatic assessment of insulin resistance was calculated in the baseline serum.</p><p><b>RESULTS</b>Type 2 diabetes mellitus was diagnosed in 15.5% of 296 CHC patients. Insulin resistance was present in 23.8% of the 235 nondiabetic CHC patients, in 23.1% of the 182 nondiabetic and noncirrhotic CHC patients, and associated with high serum HCV RNA level (OR: 1.754; 95%CI: 1.207 - 2.548, P = 0.003) and age > 40 years (OR: 3.542; 95%CI: 1.257 - 9.978, P = 0.017). Insulin resistance was less frequent in CHB than in matched CHC (7.9% vs. 21.4% respectively, P < 0.0001).</p><p><b>CONCLUSION</b>The incidence of insulin resistance in CHC was significantly higher than that in CHB patients, associated with high serum HCV RNA level and age > 40 years.</p>

Expressions of SE-1, CD31 and CD105 in the vascular endothelial cells and serum of rat with hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. In order to investigate the molecular biologic mechanism of HCC's development, we studied the expressions of SE-1, CD105 and CD31 in tumor endothelial cells (TECs) of HCC and in the serum of rats.</p><p><b>METHODS</b>We analyzed the expressions of SE-1, CD31 and CD105 in rat HCC tumor tissues using immunohistochemistry (IHC). Twenty HCC bearing rats and eighteen normal rats were examined for the expressions of SE-1, CD31 and CD105 antigens in serum by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>SE-1, CD31 and CD105 antigens were detected both in HCC tissue and in normal liver tissue with higher expressions of CD31 and CD105 in HCC while the SE-1 antigen expression was higher in normal liver. Similarly, serum CD31 and CD105 in rats with HCC were significantly increased compared with normal rats (t = 2.8628, P = 0.0086; t = 4.4922, P < 0.0001, respectively). In contrast, SE-1 antigen in HCC rat serum was significantly decreased compared with normal rats (t = 3.4983, P = 0.0011).</p><p><b>CONCLUSION</b>SE-1, CD31 and CD105 are closely related with liver tumor angiogenesis, which is similar to their performances in terms of their expressions in the serum.</p>

An analysis of clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas in patients with hepatitis C virus infection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the epidemiological and clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas (HCC) in patients with hepatitis C virus (HCV) infection.</p><p><b>METHODS</b>Eighty-nine compensated and decompensated HCV cirrhosis patients were analyzed and followed-up. The main clinical and laboratory variables were analyzed as incidence factors of HCC with univariate analysis and multivariate analysis regression models.</p><p><b>RESULTS</b>The patients were followed-up for 86 months. Thirty-five of the 89 patients had HCC during the 86 months follow-up. Their five and ten-year cumulative incidences were 16.9% and 40.4% respectively. Of the 35 HCC patients, 4 had a family history of hepatitis C, 12 had a familial history of HCC, and 7 had a history of alcohol ingestion. Five and ten-year cumulative incidences of HCC in patients with hepatic steatosis were 24.6% and 51.0% respectively. Five-year and ten-year cumulative incidences of HCC in patients with non-hepatic steatosis were 8.7% and 26.2% respectively, and the difference in the cumulative incidences between them was significant (P < 0.05). Hepatic steatosis severity was associated with the severity of the cirrhosis. ALT and TBil levels were higher in the HCC group than in the non-HCC group, ALB was lower in the HCC group than in the non-HCC group, and the differences between them were significant (P < 0.05). Child-Pugh score and the severity of the hepatic steatosis during follow-up were independently correlated with HCC.</p><p><b>CONCLUSION</b>HCC is the most important and frequent outcome of chronic hepatitis C cirrhosis. Child-Pugh score and the severity of the hepatic steatosis are related to the risk factors. History of alcohol ingestion and family history of hepatitis C are also related to liver cancer.</p>

An analysis of the pathohistology of liver tissues, clinical features and prognostic factors of chronic hepatitis B virus carriers / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the correlations between clinical features and liver pathohistological changes of chronic hepatitis B virus (HBV) carriers and to discuss the factors which may influence the prognosis.</p><p><b>METHODS</b>Ninety HBV carriers who had liver biopsies were enrolled in this study.</p><p><b>RESULTS</b>(1) The mean follow-up period of the patients was 118 weeks. (2) Fifty-four patients (60.0%) had G1 hepatitis and 21 (23.3%) had G2 hepatitis. The fibrosis stages were graded as S1(42) and S2(21). (3) There were significant age differences among S0, S1 and S2. (4) There were significant differences in aminotransferase levels between patients who had a normal liver histology and those who had mild hepatitis. (5) The grades of liver inflammation were not correlated with the titers of HBeAg and HBV DNA in sera. The stages of liver fibrosis were not correlated with the titers of HBVDNA in sera. Most of the HBeAg negative patients progressed to S2. (6) There were significant differences in spleen dimensions measured by ultrasonography between S0, S1 and S2 patients. (7) During the follow-up period serum aminotransferase (ALT) levels remained normal in 60 patients (group A); 22 patients had transient elevations (group B), and 8 patients had persistent increases (group C). There were significant differences of the ratios of S0 and S2 cases among patients in groups A, B and C. (8) Age and fibrosis stages were predictive factors of liver cirrhosis.</p><p><b>CONCLUSIONS</b>Most chronic HBV carriers had mild inflammatory histological changes in their livers and also had different degrees of liver fibrosis. This follow-up study shows that some of those carriers should have had antiviral therapy.</p>

Clinical and pathological analysis of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome / 北京大学学报(医学版)

Objective:To explore clinical and histopathological characteristics of primary biliary cirrho-sis-autoimmune hepatitis overlap syndrome.Methods:Clinical data and pathological findings of 10 pa-tients were reviewed.Results:Serum glutamine transpeptidase,alkaline phosphatase levels,alaninetransaminase,aspartate transaminase,serum IgG and IgM were elevated in all the patients.They were allpositive for anti-mitochondrial antibody and AMA-M2.Nine patients were positive for anti-nuclear anti-body and one patient was positive for anti liver-kidney microsome antibody.Liver biopsies in these pa-tients revealed:ten patients had bile duct lesion,hepatitis activities ranged from moderate to severe,andfibrosis ranged from S1 to S3.Conclusion:PBC-AIH overlap syndrome is mostly found in middle-agedwomen.It has the clinical and histopathological characteristics of both PBC and AIH.Accurate andprompt diagnosis of overlap syndrome patients should be based on the clinical presentation,biochemicaland immune indexes,and hepalic pathological changes.