Chinese Hepatolgy

Efficacy comparison of rescue therapies between TDF monotherapy and TDF-ETV combination therapy in CHB patients who failed to be rescued with ETV

LI Zhong-bin, SHAO Qing, LI Fan, LI Bing, CHEN song-hai, WANG Chun-yan, CHEN Guo-feng

2016, 21(3): 165-167.

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Objective To compare the clinical efficacy and safety between tenofovir disoproxil fumarate (TDF) monotherapy and TDF-entecavir (ETV) therapy for ETV-refractory chronic hepatitis B (CHB) patients with prior lamivudine (LAM) treatment.Methods Eighty LAM-treated CHB patients with failure of ETV rescue therapy were randomly divided into monotherapy group and combination group. The monotherapy group received TDF (300mg/d) alone for 48 weeks, while the combination group was treated with TDF (300mg/d) plus ETV (0.5mg/d). Assessment of serum hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), alanine aminotransferase (ALT) and adverse events at week 0, 12, 24 and 48 were performed to analyze therapy efficacy and adverse effects in both groups, respectively. Results After 48-week follow up, the virological response (VR) rate, biochemical response (BR) rate, virologic breakthrough (VB) rate, HBeAg seroconversion rate were 85.0% (34/40), 76.2% (16/21), 0% and 13.1% (3/23) in monotherapy group and 87.5% (35/40), 77.3% (17/22), 0% and 16.0% (4/25) in combination group, respectively (P＞0.05). There were no significant differences in all the monitoring indicators between the two groups. Both groups showed well tolerance with no serious adverse events. Conclusion The TDF monotherapy could be an effective and safe therapeutic strategy for LAM-treated CHB patients who failed to be rescued with ETV therapy.

Analysis of HBV PC mutations in ACLF patients infected with HBV combined HEV and their clinical characteristics

XIN Liang-liang, LI Bing, RONG Yi-hui

2016, 21(3): 168-171.

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Objective To study hepatitis B virus (HBV) basic core promoter and pre-C (PC) nucleotides mutations in patients coinfected with hepatitis E virus (HEV) related acute on chronic liver failure (ACLF) , and to analyze the clinical characteristics.Methods Sixty-nine cases with ACLF caused by HBV infection were retrospectively analyzed, of which 39 patients suffered single HBV infection, and the other 30 patients suffered HBV and HEV coinfection. Liver function, HBV DNA level, blood coagulation function, model for end stage liver disease (MELD) score and prognosis of the two groups were compared respectively. Polymerase chain reaction (PCR) was used for assessing HBV PC region amplification. Sequencing analysis was applied to detect reported ACLF-related mutation sites A1762T, G1764A, C1766T, T1768A, G1896A, A1762T + G1764A and G1764A + C1766T + T1768A for comparative analysis between the two groups. The survival rates and mortality of patients with HBV and HEV coinfection were evaluated for related prognostic factors by logistic regression analysis. Results In the coinfection group, total bilirubin (TBiL), incidence of hepatic encephalopathy and levels of the MELD score were significantly increased (216.4 ± 12.1 vs 364.2 ± 170.24, 17.9% vs 33.3%, 21.26 ± 6.65 vs 28.26 ± 8.65, respectively) when compared with those in single infection group, while prothrombin time activity (PTA) was obviously decreased (33.3 ± 22.4 vs 24.5 ± 20.1) (P<0.05). The comparative analysis of HBV-PC mutation sites A1762T (66.7% vs 76.7%), G1764A (69.2% vs 80.0%), A1762T+G1764A (59.0% vs 70.0%) and G1764A+C1766T+T1768A (2.6% vs 10.0%) showed statistically differences between the two groups (P<0.05). Additionally, among HBV and HEV coinfection patients, the MELD score and incidence of hepatic encephalopathy in death group increased significantly when compared to those in survival group, but the PTA decreased obviously (P<0.05). The comparative analysis of HBV-PC mutation site G1764A + C1766T + T1768A triplet mutation also showed significant difference (P<0.05) between the two groups in patients with coinfection. The logistic regression analysis suggested that TBiL (P=0.006, OR=2.672), PTA (P=0.036, OR=2.115), MELD score (P=0.003, OR=1.682), hepatic encephalopathy incidence (P=0.001, OR=3.631) and G1764A + C1766T + T1768A triplet mutation (P=0.043, OR=0.043) were all related to the prognosis.Conclusion The prognosis is poor in ACLF patients caused by HBV and HEV coinfection, which could be indicated from high TBiL level, MELD score, incidence of hepatic encephalopathy and HBV-PC area G1764A+C1766T+T1768A triplet mutation rate. Furthermore, lower PTA level always predicts a worse prognosis.

The application of dual-wire one-step puncture and percutaneous portal vein puncture portography in TIPS

LU Xin, ZENG Guo-bin, ZOU Mei-hua

2016, 21(3): 172-175.

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Objective To investigate the operational approach and value of dual-wire one-step puncture and percutaneous portal vein puncture portography in transjugular intrahepatic portosystemic shunt (TIPS).Methods Twenty-one cirrhosis patients with gastroesophageal varices bleeding received treatment with TIPS by dual-wire one-step puncture and percutaneous portal vein puncture portography. Results All of these patients were successfully operated on with TIPS, with average operation time of (152.41±50.38) min and surgery puncture times of (2.50±1.54). Meanwhile, TIPS treatment significantly attenuated the portal venous pressure and liver function, with success rate as 100% and mortality as 5%.Conclusion The method of TIPS using dual-wire one-step puncture and percutaneous portal vein puncture portography could reduce operation difficulty, which is worth to be popularized and applied.

The diagnostic significance of MRI and ADC for hepatocellular adenoma

LI Ming-tong

2016, 21(3): 176-178.

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Objective To analyze the diagnostic significance of magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) for hepatic adenoma. Methods Twenty-one cases pathologically confirmed as hepatic adenoma were enrolled for comparison analysis between preoperative biopsy, MRI performance and ADC. Results Among the 21 cases, 19 and 2 cases were preoperatively diagnosed as benign liver adenomas and focal nodular hyperplasia, respectively; 2 cases were accompanied with cirrhosis; 1, 5 and 15 cases had 9, 2 and single lesions, respectively. In terms of the 34 lesions, 26 had high lipid content, while 8 had low lipid content. Additionally, there were 18 lesions with less than 3cm in diameter, 10 with 3-5cm and 6 with more than 5cm. The T1WI scan signals were low in 30 lesions and high in 4, and the T2WI scan signals were low in 11 lesions and high in 23. Gd-DTPA enhanced scan showed that the signals were significantly strengthened during the arterial phase, were low in 12 lesions and high in 22 during the portal venous phase, and were low in 12 lesions and high in 22 in the delayed phase. Moreover, diffusion weighted imaging (DWI) scan showed that the signals were low in 21 lesions and high in 13. Pseudocapsule-like enhancing lesions were observed in 14 lesions, and the other 20 ones displayed as no clear signs. The ratio of mean ADC value of 34 lesions to the value of their surrounding normal liver parenchyma was more than 1 [(1.704±0.33)×10^-3mm²/s vs. (1.357±0.214)×10^-3mm²/s]. Conclusion MRI combined with ADC value measurements could provide reliable references for the diagnosis of hepatic adenoma and improve the accuracy of clinical diagnosis.

Study on microRNA-218 inhibiting proliferation of hepatocellular carcinoma cell by down-regulating E2F2 gene expression

WANG Tao, MA Si-cong, QI Xing-xing, TANG Xiao-yin, CUI Dan, WANG Zhi, CHI Jia-chang, LI Ping, ZHAI Bo

2016, 21(3): 179-182.

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Objective To investigate the mechanism for microRNA-218 (miR-218) dampening E2F2 gene expression to inhibit proliferation in hepatocellular carcinoma (HCC).Methods HCC cell lines (HepG2, Huh7, MHCC.97H and BEL.7402) and normal hepatocyte cell line L02 were obtained from cell bank, which were subjected for reverse transcription-polymerase chain reaction, immunoblot analysis, cell proliferation and colony formation test, cell cycle analysis and relevant statistics analysis. Results The miR-218 level was down-regulated in cancer cells (P<0.05). The growth curve of MTT indicated that proliferative capacity of cells was significantly reduced in miR-218-overexpressed cells (Huh7: P=0.001; MHCC.97: P=0.013). These results revealed that E2F2 was the direct target of miR-218. In comparison to control group of L02, the relative mRNA of E2F2 in Huh7 and MHCC.97 cell lines transfected with the stimulant of miR-218 was significantly down-regulated (P<0.05). Conclusion miR-218 can directly act on the 3' untranslated region of E2F2 gene to inhibit the development of HCC.

Effects of salvianolic acid B and hawthorn flavone on lipid deposition and apoptosis of hepatocytes in rats induced by free fatty acids

XUE Dong-ying, XI Bo-ren, ZHANG Jie, YE Jun

2016, 21(3): 183-190.

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Objective To investigate the effects of salvianolic acid B and hawthorn flavone on free fatty acids (FFA)-induced lipid deposition and apoptosis of hepatocytes in rats, and its potential mechanism.Methods HepG2 cells and primary cultured hepatocytes isolated from male SD rats by collagenase perfusion were subjected for this study. Oleic acid and palmitic acid (O∶P=2∶1) were used to induce nonalcoholic steatohepatitis (NASH) in primary cultured hepatocytes and HepG2 cells, respectively. The cell models were divided into 11 groups, including normal control group, FFA group, FFA + salvianolic acid B group, FFA+ hawthorn flavone group, FFA + salvianolic acid B + hawthorn flavone group, FFA+ SP600125 group, salvianolic acid B group, hawthorn flavone group, hawthorn flavone + salvianolic acid B group, SP600125 group and DMSO control group, respectively. Correspondingly, the cell models of NASH in primary cultured hepatocytes and HepG2 cells were stimulated with different doses of FFA (250 μmol/L and 500 μmol/L ), salvianolic acid B (10-6mol/L), hawthorn flavone (5 μg/mL) and SP600125 (10 μmol/L), respectively. In order to evaluate the therapy effects of salvianolic acid B and hawthorn flavone against NASH, the following tests were performed: Oil Red O staining for lipid deposition, and enzyme-linked immune-sorbent assay (ELISA), chromatin dye and Hoechst 33258 staining for apoptosis. In addition, it was speculated that the therapy effect was associated with c-Jun N-terminal kinase (c-JNK), which was verified by western blot to assess the expression of phosphorylated-JNK (p-JNK). Results After 24h of incubation with FFA alone, lipids in primary cultured hepatocytes and HepG2 cells were significantly increased (P<0.01). Moreover, salvianolic acid B, hawthorn flavoneor and SP600125 sharply reduced lipids deposition, respectively (P<0.01,P<0.05). The intracellular lipids in DMSO control group had no significant difference than that in normal control group. ELISA showed that FFA induced apoptosis in primary hepatocytes and HepG2 cells (P<0.01). Meanwhile, salvianolic acid B, hawthorn flavone or SP600125 could significantly protect liver from FFA-induced apoptosis (P<0.05, P<0.01). Through chromatin dye and Hoechst 33258 staining, FFA-induced apoptosis in primary cultured hepatocytes and HepG2 cells was also observed under high content screening (HSC) (P<0.01). Salvianolic acid B and hawthorn flavone could significantly reduce the apoptosis (P<0.05, P<0.01), respectively. Western blot analysis showed that FFA treatment led to a significant increase in c-JNK activity (P<0.01) in primary cultured hepatocytes and HepG2 cells, while total JNK levels remained unchanged. Meanwhile, salvianolic acid B and hawthorn flavone could significantly reduce the JNK activity.Conclusion Salvianolic acid B and hawthorn flavone could alleviate FFA-induced apoptosis and lipid metabolism disorders, respectively. Furthermore, they could also inhibit JNK activity, which reveals an important molecular mechanism for treatment of NASH.

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