Table of Content

31 May 2016, Volume 21 Issue 5

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Original Articles

Analysis of telbivudine treatment induced creatine kinase elevation in patients with chronic hepatitis B

CHEN Juan, ZHAO Hong-wen, DENG Ling, ZHU Yan, ZHANG Chang-jiang, WANG Xiao-hong

2016, 21(5):  334-337. 

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Objective To investigate clinical features of tebivudine (LdT) induced creatine kinase (CK) elevation and its risk factors in chronic hepatitis B (CHB) patients, and to evaluate safety of LdT.Methods A total of 527 CHB patients were enrolled in this study, and their clinical data was retrospectively analyzed. Among these patients, 91 received LdT plus adefovir dipivoxil (ADV) therapy and 436 received LdT monotherapy, including 19 with CHB concomitant chronic renal disease (CKD) and 58 pregnant women. The CK levels and muscle symptoms were dynamically observed, and virus, immune and biochemical markers both at baseline and the end of therapy were detected, respectively.Results Variable degrees of CK elevation occurred in 321 cases (60.91%), in which 281 cases (53.32%) were in grade 1-2 and 40 cases (7.59%) were in grade 3-4. Additionally, 14 patients (2.65%) were diagnosed as myositis. In patients with CK elevation of grade 3-4, there was no significant difference between the 2 groups (P=0.16). Male was a risk factor for CK elevation with LdT treatment(P<0.001), while pregnance and CKD were protective factors (P<0.001; P=0.003).Conclusion It is quite common of CK elevation in CHB patients treated with LdT, which suggests that strengthening monitor of CK is indispensable for avoiding LdT-induced serious adverse effects. In regard to LdT-induced CK elevation, application of LdT in HBV-infected pregnant women and patients with CHB concomitant CKD might be safe.

The evaluation study acoustic pulse radiation force imaging in acute drug-induced liver injury

YANG Ke-ke, LIAO Jin-tang

2016, 21(5):  338-340. 

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Objective To investigate the application value of acoustic pulse radiation force imaging (ARFI) in acute drug-induced liver injury.Methods Eight-nine patients with acute drug-induced liver injury (liver injury group) admitted from January 2013 to November 2015 in our hospital and 60 healthy persons (healthy control group) were randomly enrolled as the study objects. Among all cases, ultrasound contrast examination and ARFI examination were performed, and liver function indexes were detected, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-alanine aminotransferase (GGT), albumin (Alb), and so on. Shear wave speeds of left, right anterior and right posterior liver lobes were compared between the 2 groups, respectively. Furthermore, patients in liver injury group were divided into 3 subgroups, among which comparisons of the shear wave speed and liver function indexes were conducted, respectively. And correlation analysis between shear wave speed and liver function indexes was carried out by Spearman correlation coefficient.Results The shear wave speeds of the left lobe, right anterior lobe and right posterior liver lobes in liver injury group were higher than those in healthy control group, respectively, which showed significant difference (P<0.05). However, the comparisons of shear wave speeds among left lobe, right anterior lobe and right posterior lobe within each group had no significant difference (P>0.05), respectively. Comparisons of shear wave speed and liver function indexes among the three subgroups showed significant differences (P<0.05). Shear wave speed showed a rising trend from group C to group B and to group A, so did ALT, AST, GGT, alkaline phosphatase (ALP), Alb; gamma globulin (GLB) showed a rising trend from group A to group B and to group C. Moreover, the shear wave speed had a positive correlation with ALT, AST, GGT, ALP and ALb (r values were respectively 0.518, 0.309, 0.715, 0.474 and 0.691, P<0.05), respectively, and a negative correlation with GLB (r=-0.412, P<0.05), which revealed that shear wave speed increased with aggravation of liver function injury. For acute drug-induced liver injury diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accurate rate of ARFI were 89.9% (80/89), 90.0% (54/60), 90.3% (80/86), 85.7% (54/63), 89.9% (134/149), respectively.Conclusion AFRI might be helpful in differential diagnosis and pathological typing of acute drug-induced liver injury, which is worthy of clinical promotion and application.

Effects of adefovir dipivoxil on serum phosphate level and bone mineral density in patients with chronic hepatitis B

LIU Yu-zhu, MIN Xiang-xi

2016, 21(5):  341-343. 

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Objective To investigate hypophosphatemia in chronic hepatitis B (CHB) patients with adefovir dipivoxil treatment, and its effect on bone mineral density.Methods One hundred and forty-eight CHB patients who had received adefovir dipivoxil treatment over 2 years were enrolled in the study. Fasting peripheral blood were collected for detection of phosphorus concentration, then high risk factors for hypophosphatemia and its effects on abnormal bone mineral density were analyzed.Results Among the 148 patients, hypophosphatemia occurred in 42 cases (28.4%) and abnormal bone mineral density was detected in 35 cases (23.6%). Age over 60 and continuous medication of adefovir dipivoxil for more than 48 months were high risk factors hypophosphatemia. The incidence of abnormal bone mineral density in patients with hypophosphatemia was higher than that in patients with normal serum phosphate levels (χ²=60.101, P<0.05). Level of serum phosphorus showed significantly negative correlation with incidence rate of abnormal bone mineral density (P<0.05).Conclusion Long-term medication of adefovir dipivoxil for CHB patients can lead to kidney damages with manifestation of hypophosphatemia, hypophophatemic oestemalacia, osteoporosis and other bone mineral density anomaly symptoms.

Application and diagnostic value of contrast-enhanced ultrasonography and color Doppler flow imaging for hepatic focal nodular hyperplasia

ZHANG Shu, ZHAO Hong-zhen, LAN Hai-feng

2016, 21(5):  344-346. 

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Objective To investigate the application and diagnostic value of contrast-enhanced ultrasonography (CEUS) and color Doppler flow imaging (CDFI) for hepatic focal nodular hyperplasia (FNH).Methods Thirty-two patients with FNH admitted from May 2014 to June 2015 were enrolled to receive CEUS and CDFI, and their characteristics were retrospectively analyzed.Results Among the 32 cases, CEUS showed that lesions enhancements arose at 12-16 s and quickly homogeneously perfused in arterial phase, including 24 cases of central type with spoke-like enhancements, 8 of integral type with 5 eccentric and 3 mass-like enhancements. In portal phase, most cases manifested as high echo, while a few of cases showed equal or low echo, including 1 of visible hypoechoic central scar. In delayed phase, it showed high echo in 18 cases (18/36), equal echo in 10 cases (10/32) and low echo in 4 cases (4/32). CDFI revealed 37 positive lesions in these patients, including single lesion in 28 cases (28/32) and multiple lesions in 4 cases (4/32). Most hyperplastic nodules were uniformly distributed in the right hepatic lobe. The diameter of intrahepatic nodules was 3.4 cm in average, ranging from 2.5 to 5 cm. Intrahepatic nodules were hypoechoic in 4 cases (4/32), slightly hypoechoic in 3 (3/32), hyperechoic in 8 (8/32), slightly hyperechoic in 14(14/32) and isoechoic in 2 (2/32). The nodules were roundish in 26 cases (26/32) and irregular in 6 (6/32), with clear boundaries in 19 cases (19/32), obscure in 10 (10/32) and surrounding acoustic halo in 3 cases (3/32). Color Doppler ultrasound examination showed low-resistance artery flow spectrum in all lesions, with 22 cases of typical spoke-and-wheel blood flow signals.Conclusion CEUS and CDFI dynamically demonstrates the characteristics of blood perfusion in FNH lesions, which might play crucial roles in diagnosis and differential diagnosis of FNH.

Genetic polymorphisms of microRNA-4293 and hepatocellular carcinoma susceptibility in female

CAI Min, ZHENG Wan-wei, ZHANG Jun, CHENG Feng-tao, LI Li

2016, 21(5):  347-350. 

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Objective To investigate the association between single nucleotide polymorphism (SNP) mapping to microRNA-4293 (rs12220909) and hepatocellular carcinoma (HCC) susceptibility.Methods Blood samples were collected from 1788 cases, including 884 normal control cases and 904 HCC cases. Genomic deoxyribonucleic acid was extracted from blood samples, and SNPs mapping to microRNA-4293 (rs12220909) were detected by MassARRAY. Then association between genotype of rs12220909 and HCC susceptibility was analyzed by binary logistic regression.Results In female HCC patients, CC genotype of rs12220909, especially in hepatitis B virus (HBV)-related HCC patients (P=0.02), was significantly higher than that in healthy control group (P=0.04). It indicated that CC genotype might be a risk factor for female HCC, especially for HBV-related HCC. However, this association did not exist in male patients (P=0.33).Conclusion Genotype of microRNA-4293 (rs12220909) is relevant to HCC in female patients.

Establishment of acetaminophen-induced acute hepatic failure model in mice

MING Ya-nan, LI Chun-min, ZHANG Jing-yi, LIU Xiao-lin, MAO Yi-min

2016, 21(5):  351-354. 

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Objective To establish a stable animal model of drug-induced acute hepatic failure (AHF) with different doses of acetaminophen (APAP) by intraperitoneal injection.Methods Sixty mice, which were randomly divided into four groups (n=15), were intraperitoneally injected with saline and different doses of APAP (300 mg/kg, 500 mg/kg and 750 mg/kg), respectively. Mental status, activity and survival rates in different groups were observed within 72 hours. According to the analysis of survival rates, another 180 mice were divided into three groups randomly (n=60) with injection of saline, low (300 mg/kg) and high dose (750 mg/kg) of APAP, respectively. To detect the biochemical and pathological changes of AHF, 12 mice randomly selected from each group were sacrificed for serum and liver tissues collection at 0 h, 1 h, 3 h, 6 h and 12 h after injection, respectively.Results No mice died within 72 h in the control group, APAP (300 mg/kg and 500 mg/kg group) , while the mortality of APAP 750 mg/kg group was 100%. In control group, aminotransferase (ALT) level showed no significant increase at all time points. However, ALT levels in two APAP groups (300 mg/kg and 750 mg/kg) began to increase at 3 h, and reached to peak at 6 h (6766.5±2001.27 IU/L) or 12 h (11707.58±1882.45 IU/L) in low-dose or high-dose APAP group, respectively. Additionally, ALT level in high-dose APAP group was significantly higher than that in low-dose APAP group at 12 h (P<0.01). In view of haematoxylin-eosin (HE) staining, control group displayed normal liver structure. In APAP group, degeneration and necrosis of hepatocytes mainly occurred around central vein, and damage extent gradually expanded over time. In low-dose group, boundaries of necrotic zones were clear with normal liver cell morphology in portal areas, and visible hepatocytes proliferation around the boundaries was observed at 12 h. In high-dose group, typical acute massive hepatic necrosis was found and few of degenerated hepatocytes stayed alive at portal areas. After rapid necrosis of hepatocytes, empty fiber mesh stent remained with large red blood cells deposited in sinusoids and no proliferation of hepatocytes. At 12 h, histological activity index (HAI) score of high-dose group (7.33±1.5) was higher than that of low-dose group (5.25±2.26), which showed statistically significant differences (P<0.05).Conclusion C57BL/6 mice injected with high dose of APAP (750 mg/kg) have similar biochemical and pathological changes with AHF, which might be a reliable AHF model for investigating the role of APAP in pathogenesis and development of liver failure.

Ultrasound-guided percutaneous microwave ablation as first-line treatment for HCC: A study on clinical efficacy and prognostic factors

MA Si-cong, WANG Tao, DING Min, MING Ya-nan, QI Xing-xing, ZHANG Yuan, ZHAI Bo

2016, 21(5):  355-359. 

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Objective To investigate the clinical efficacy of ultrasound (US)-guided percutaneous microwave ablation as a first-line treatment for hepatocellular carcinoma (HCC), and its prognostic factors analysis.Methods From June 2010 to November 2014, 201 patients who were first diagnosed HCC and receiving US-guided microwave ablation treatment in Shanghai Renji hospital were enrolled, and followed up for 4 to 53 months. Univariate (Kaplan-Meier method) and multivariate (Cox-regression) analysis were applied to determine the prognostic factors for progression-free survival and overall survival.Results Complete ablation rate after first ablation was 96%. For some patients receiving a second ablation, the total complete ablation rate was 99%. Twelve of the 201 (5.6%) patients suffered ablation associated complications. Mean progression-free survival (PFS) of microwave ablation therapy was 18 months. In addition, liver function Child B, multiple tumors, tumor diameter > 5 cm and AFP>20 were independent risk factors associated with worse PFS. Hepatitis history, multiple tumors and tumor diameter > 5cm were independent predictors for overall survival (OS) of which mean value was 38 months.Conclusion US-guided microwave ablation as a first-line therapy for HCC is safe and efficacious. Tumor diameter, tumor number and liver status of patients might be main prognostic factors affecting PFS and OS.