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1.
Zhonghua Gan Zang Bing Za Zhi ; 28(12): 1013-1017, 2020 Dec 20.
Article in Chinese | MEDLINE | ID: mdl-34865348

ABSTRACT

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Neoplasms , Adult , DNA, Viral , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Retrospective Studies , Viral Load
2.
Chemotherapy ; 54(6): 431-7, 2008.
Article in English | MEDLINE | ID: mdl-18824850

ABSTRACT

BACKGROUND: Gallbladder cancer is a common and lethal digestive malignancy which is nonsensitive to routine chemotherapy. Doxorubicin (DOX) is one of the major chemotherapeutic drugs for patients with gallbladder cancer. We tried to evaluate if combined use of somatostatin (SST) and DOX could have synergistic effect in the treatment of gallbladder cancer. METHODS: Cells from the human gallbladder cancer cell line GBC-SD were treated with SST. Cell cycle analysis was determined by flow cytometry. Western blot analysis was performed to determine the protein levels of topoisomerase IIalpha (Topo IIalpha) after SST treatment. RT-PCR was utilized to detect SST receptors in GBC-SD cells. Finally, the chemotherapeutic effect of DOX combined with SST treatment on cellular growth was measured by MTT assay. RESULTS: SST could induce cell cycle arrest in S phase and upregulate Topo IIalpha expression in GBC-SD cells. GBC-SD cells expressed all 5 subtypes of SST receptors. Finally, combined use of DOX with SST had a synergistic cytotoxic effect on GBC-SD cells. CONCLUSION: SST, a naturally occurring, nontoxic compound, may represent a novel adjuvant chemotherapeutic agent for patients with gallbladder cancer.


Subject(s)
Antigens, Neoplasm/metabolism , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/antagonists & inhibitors , DNA-Binding Proteins/metabolism , Doxorubicin/toxicity , Gallbladder Neoplasms/enzymology , Gallbladder Neoplasms/pathology , Gene Expression Regulation, Enzymologic/drug effects , Somatostatin/pharmacology , Topoisomerase II Inhibitors , Cell Cycle/drug effects , Cell Line, Tumor , Humans , RNA, Messenger/genetics , Receptors, Somatostatin/metabolism , Up-Regulation/drug effects
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