Efficacy of a Chinese herbal formula on hepatitis B e antigen-positive chronic hepatitis B patients.

BACKGROUND: No guideline recommends antiviral therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus (HBV) DNA viral load. AIM: To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection. METHODS: In total, 395 patients (30-65 years old) with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk. Endpoints to evaluate therapeutic efficacy included: (1) HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96; and (2) HBeAg clearance and seroconversion rates at weeks 48 and 96. RESULTS: HBV DNA levels ≤ 4 log10 IU/mL were 10.05% at week 48 and 18.59% at week 96 in the treatment group. The HBeAg clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96, respectively. However, HBV DNA levels ≤ 4 log10 IU/mL were 2.55% and 2.55% at weeks 48 and 96, respectively, and the HBeAg clearance rates were 3.06% and 5.61% at weeks 48 and 96, respectively, in the control group. The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance. CONCLUSION: High rates of HBV DNA reduction, HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments, and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase. The ability of the compound to modulate host immune function probably contributed to this effect.

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China.

BACKGROUND: The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy. METHODS: Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak's fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out. RESULTS: Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30-39, 40-49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3). CONCLUSION: Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARα and L-FABP Expressions in High-Fat-Fed Rats.

This study aimed to investigate the effects of Shugan Xiaozhi decoction (SX) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet in rats. The rats were randomly divided into 6 groups, namely, control, model, fenofibrate, and three different dosage of SX (10, 20, and 40 g/kg/day, p.o.). After establishing the NASH model, at 8 weeks of the experiment, treatments were administrated intragastrically to the fenofibrate and SX groups. All rats were killed after 4 weeks of treatment. Compared with the model group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL) serum in the serum were significantly reduced in all SX treatment groups in a dose-dependent manner. Evidence showed that SX could protect the liver by upregulating the gene and protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and liver fatty acid binding protein (L-FABP) in a dose-dependent manner. Chemical constituents of SX were further analyzed by ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS) and 30 chemicals in the ethanolic extract were tentatively identified. To conclude, our results clearly indicated that SX could protect liver functions and relieve hepatic steatosis and inflammation.

Serosa-penetration in human T4aN0M0 gastric carcinoma correlates with worse prognosis after D2 gastrectomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In both the seventh edition of the International Union Against Cancer (UICC) staging system for gastric cancer and the 14th edition of the Japanese Gastric Cancer Association (JGCA) system, T(4a) is defined as "Tumor perforates serosa (visceral peritoneum) without invasion of adjacent structures." The aim of this study was to investigate the differences in prognosis between patients with serosa-penetrating and serosa-invading T(4a)N(0)M(0) gastric carcinomas.</p><p><b>METHODS</b>Data were collected from 221 patients with T(4a)N(0)M(0) gastric carcinoma who underwent D2 resection at our cancer center between January 1990 and December 2008. The cohort included 42 patients with serosa-penetrating tumors and 179 patients with serosa-invading tumors. The average follow-up time was 85.5 months. Spearman's rank correlation, Kaplan-Meier plots, and Cox proportional hazards regression models were used to analyze the data.</p><p><b>RESULTS</b>The 5-year survival rate of patients with serosa-penetrating and serosa-invading gastric cancers were 31% and 62% respectively (P < 0.05). The relapse rates after D2 radical surgery were 16.2% in patients with serosa-invading gastric cancer versus 59.5% in those with serosa-penetrating tumors (P < 0.05). Peritoneal dissemination and distant organ/lymph node metastatic rates were 76.0% and 24.0% respectively in patients with penetrating tumors, versus 44.8% and 55.2% respectively in patients with invading tumors (P < 0.05). Multivariate analysis showed that penetration of the serosa was an independent prognostic indicator of overall survival.</p><p><b>CONCLUSIONS</b>Our findings provide a basis for the concept that serosa-penetrating T(4a)N(0)M(0) gastric carcinoma represents a more aggressive cancer than serosa-invading T(4a)N(0)M(0) gastric carcinoma. Serosa penetration is an independent factor for poor prognosis of patients with gastric carcinoma.</p>

Comparison of two types of digestive tract reconstruction after total gastrectomy in patients with gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the influence of two different types of digestive tract reconstruction on the life quality, nutritional status and tolerance to adjuvant chemotherapy after total gastrectomy in patients with gastric carcinoma.</p><p><b>METHODS</b>The clinical data of a total of 107 patients treated in our department from January 2005 to december 2008 were analyzed retrospectively. Among them, 49 patients underwent digestive tract reconstruction with functional jejunal interposition (FJI group) and 58 patients underwent Roux en-Y jejunal P-type anastomosis (PR group) after total gastrectomy. 79 of 107 (73.8%) patients received postoperative adjuvant chemotherapy with XELOX regimen. The digestive complications and tolerance to chemotherapy were assessed respectively.</p><p><b>RESULTS</b>Neither severe complications nor surgery-related or chemotherapy-related death were observed among the 107 patients. There were statistical differences in the incidence rate of emaciation, dumping syndrome and retention syndrome between the FJI and PR groups (P < 0.05), but no significant statistical difference in incidence rate of reflux esophagitis (P > 0.05). 28 of 40 (70.0%) patients in the FJI group completed all six cycles of chemotherapy, while 12 (30.0%) patients interrupted the treatment due to chemotherapy-related toxicity. 39 patients in the PR group received chemotherapy, 19 (48.7%) of them completed 6 cycles of chemotherapy but 20 (51.3%) patients interrupted. There was a significant difference in the incidence rate of grade III/IV chemotherapeutic toxicity and completion rate of chemotherapy (P < 0.05).</p><p><b>CONCLUSIONS</b>Both functional jejunal interposition and Roux-Y operation are reasonable and safe procedures of digestive tract reconstruction. The incidence rates of emaciation, dumping syndrome and retention syndrome are lower in the patients with FJI, showing a better tolerance to adjuvant chemotherapy than Roux en-Y jejunal p type anastomosis.</p>

Relationship between the number of lymph node detection and prognosis in stage II gastric cancer after D(2) dissection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between the lymph node count and prognosis in stage II gastric cancer.</p><p><b>METHODS</b>Retrospective analysis was performed for the 268 cases with gastric cancer who underwent parallel D(2) dissection between January 1990 and December 2006 in the Sun Yat-Sen Cancer Center. The Japanese Gastric Cancer Association(JGCA) 13th edition of pathological staging system was used to define stage II gastric cancer. Patients were followed up until December 2008. The Kaplan-Meier method and chi-square test were used for data analysis. All the data were analyzed using SPSS16.0 for Windows.</p><p><b>RESULTS</b>The average number of detected lymph nodes was 17.3+/-1.2. There were 109 patients with detected lymph node <15. The 1-, 3-, and 5-year survival rates were 92.7%, 67.8%, and 50.9%, respectively. The number of detected lymph node was > or =15 in 159 cases, and the 1-, 3-, and 5-year survival rates were 96.9 %, 81.0%, and 66.4%, respectively. The difference between two groups was statistically significant (P=0.003). Further analysis of the 199 cases with no lymph node metastasis (pN(0) group) showed that there were 95 cases with lymph nodes <15, and the 1-, 3-, and 5-year survival rates were 92.6%, 70.4%, and 55.9%, respectively. There were 104 patients with > or =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 97.1%, 84.4%, and 66.8%, respectively. The difference was also statistically significant (P=0.049). There were 69 cases with lymph node metastasis (PN(1) group), and the 1-, 3-, and 5-year survival rates of 14 patients with lymph nodes <15 were 92.9%,57.1%, and 34.3%, respectively. Comparing two groups, the survival rate was significantly different (P=0.034). There were 55 patients with > or =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 96.4%, 73.4%, and 63.8%. The difference was statistically significant (P=0.036).</p><p><b>CONCLUSION</b>In patients with stage II gastric cancer as defined by the JGCA 13th edition, the survival rate is better in patients with more than 15 detected lymph nodes as compared to those with less than 15.</p>

[Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma and their significance in clinical settings].

OBJECTIVES: To identify serologic markers that may indicate the early presence of hepatocellular carcinoma (HCC), and analyze their significance in the pathogenesis of chronic hepatitis B. METHODS: Hepatitis B x antigen (HBxAg) positive and negative HepG2 cells were subjected to PCR select cDNA subtraction to identify differentially expressed genes that may precede the development of HCC. These included the up-regulated genes URG4, URG7, URG11, and VEGFR3, and the down-regulated gene, Sui1. Specific ELISAs were constructed to measure differentially expressed antigens and their corresponding antibodies to determine whether they had prognostic and/or diagnostic value. The study population consisted of 730 people. Among them, 416 were HBsAg(-) and 298 were HBV carriers with chronic liver disease and/or HCC. In addition, 16 patients had non-viral hepatitis. Among these, serial serum samples from 53 HBsAg(+) patients with cirrhosis were collected and studied. RESULTS: Antibodies to multiple differentially regulated genes were detectable in serum samples from patients with HBV associated cirrhosis and HCC, but not in serum samples from uninfected individuals (P < 0.01). Antibodies were undetectable in serum samples from HBV patients without liver disease and in serum samples from patients with other tumor types, and among those with non viral hepatitis. Among patients at high risk of developing HCC, these antibodies were found to be independent of nationality and ethnicity. Statistical analysis of the 28 HBsAg(+) patients with HCC showed that anti-URG11 and anti-VEGFR3 were the most frequently detected antibodies. These antibodies were found to coexist in 16 (P < 0.05). In contrast, among the 25 HBsAg(+) patients without HCC, anti-Sui1 and anti-URG7 were the most prevalent antibodies. These antibodies coexisted in 11 (P < 0.05). In addition, HCC patients with four or more antibodies detected before the appearance of HCC had a poorer survival outcome. CONCLUSION: These antibodies can be detected in serum samples several months to several years before the appearance of HCC. This suggests that they may be preneoplastic markers that may help to distinguish which HBV carriers with cirrhosis are most likely to progress and develop HCC.