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1.
Goto T Yoshida H Tateishi R Enooku K Goto E Sato T Ohki T Masuzaki R Imamura J Shiina S Koike K Omata M 《Hepatology International》2011,5(3):767-773
Background
High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is a strong risk factor of hepatocellular carcinoma (HCC) development, independent of hepatitis B e antigen, serum alanine aminotransferase level, and liver cirrhosis. We evaluated whether serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC treated with radiofrequency ablation (RFA).Methods
The study population was 69 consecutive patients with HBV-related HCC treated locally completely with RFA between January 2000 and September 2007. The risk factors for HCC recurrence were analyzed based on laboratory data, including serum HBV DNA load, together with tumor size and number using univariate and multivariate proportional hazard regression analyses.Results
HCC recurrence was observed in 42 of 69 patients during the median observation period of 1.5 years. Cumulative recurrence rates at 1, 3, and 5 years were 26.5, 57.8, and 74.3%, respectively. In univariate analysis, albumin (<3.5 g/dl), platelet count (<150 × 103/mm3), prothrombin activity (PT) (<70%), Child-Pugh class B, serum HBV DNA load (>4.0 log10 copies/ml), and tumor number (>3) were associated with the recurrence at p ≤ 0.15. Multivariate Cox regression analysis with stepwise variable selection showed that the tumor number (risk ratio, 4.63; 95% CI, 1.50–14.25, P = 0.0076), low PT (3.39, 1.52–5.78, P = 0.0029), and high HBV DNA load (2.67, 1.16–6.14, P = 0.021) were independent risk factors for HCC recurrence.Conclusion
Serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC after RFA. 相似文献2.
Zhoujing Zhang Shengxiang Ge Xiaomin Wang Quan Yuan Qiang Yan Huiming Ye Yaojian Che Yanyan Lin Jun Zhang Pingguo Liu 《Hepatology International》2013,7(1):199-207
Background and goals
There are no highly sensitive and specific minimally invasive biomarkers for hepatocellular carcinoma (HCC) to date. The objective of this study was to identify serum microRNAs (miRNAs) as potential HCC biomarkers.Methods
Using miRCURY LNA? microRNA arrays, the levels of circulating miRNAs in the serum of patients with HCC were compared and controls were matched. Then 253 subjects (112 HCC, 85 chronic hepatitis B [CHB], and 56 healthy controls) were recruited and 12 serum miRNAs were compared by quantitative real-time polymerase chain reaction (qRT-PCR). It was followed by the comparison of serum miRNA concentrations before and after the surgical resection in HCC group.Results
Median levels of miR-483-5p and miR-500a were higher in HCC patients than in patients with CHB and in healthy controls (p < 0.0001), but there were no differences between CHB patients and healthy controls (p > 0.05) and miR-483-5p levels were significantly reduced in serum samples obtained 30 days after surgical resection (p < 0.0001). The area under receiver operating characteristic curves of miR-483-5p and miR-500a was 74% (cutoff [Ct] value = 2.824, sensitivity = 74%, and specificity = 66%) and 66% (Ct value = 1.830, sensitivity = 74%, and specificity = 51%) for the prediction of HCC, respectively. In detecting HCC, combining α-fetoprotein (AFP) and serum miR-483-5p (sensitivity = 81% and specificity = 83%) was better than AFP alone (sensitivity = 78%, specificity = 70%).Conclusion
Our observations suggest that serum miR-483-5p and miR-500a might serve as novel, noninvasive biomarkers for HCC. Serum miR-483-5p might complement AFP in detecting HCC. 相似文献3.
Yun-Hsuan Lee Chia-Yang Hsu Cheng-Yuan Hsia Yi-Hsiang Huang Chien-Wei Su Yi-You Chiou Han-Chieh Lin Teh-Ia Huo Shou-Dong Lee 《Hepatology International》2013,7(2):645-654
Background/Aims
Chronic hepatitis B and hepatitis C virus (HBV, HCV) infection and alcoholism are common etiologies for hepatocellular carcinoma (HCC). The characteristics and impact of alcoholism and/or HCV/HBV infection on HBV- and HCV-related HCC, respectively, are investigated in this study.Methods
A total of 1,888 patients were retrospectively investigated and categorized into six groups, HBV only (n = 977), HBV with alcoholism (n = 197), HCV only (n = 544), HCV with alcoholism (n = 67), dual HBV and HCV (n = 82), and dual virus with alcoholism (n = 21), to examine their interactions on the outcome.Results
Compared to their counterparts, alcoholic patients coinfected with HBV and/or HCV tended to be younger, had higher male-to-female ratios, worse performance status, more severe liver cirrhosis, advanced cancer staging, and tumor burden than patients without alcoholism. In survival analysis, patients with HBV with alcoholism had a significantly decreased survival than the HBV-only group (p = 0.001). A shortened survival was also observed in HCV with alcoholism group compared to the HCV-only group (p = 0.011). Dual virus infection with alcoholism did not significantly worsen the survival compared to the dual virus infection group. In the Cox proportional hazards model, HBV with alcoholism group [risk ratio (RR) 1.299, p = 0.032] and HCV with alcoholism (RR 1.523, p = 0.025) group were independent predictors associated with decreased survival compared to their counterpart of HBV- and HCV-only groups.Conclusions
Alcoholism in patients with HBV or HCV infection is characterized by early development of HCC with advanced cirrhosis and cancer staging at diagnosis. Alcoholism independently predicts an increased risk of mortality in patients with HBV- and HCV-related HCC. 相似文献4.
Hung HH Su CW Lai CR Chau GY Chan CC Huang YH Huo TI Lee PC Kao WY Lee SD Wu JC 《Hepatology International》2010,4(4):691-699
Purpose
Although advanced liver fibrosis is crucial in the development of hepatocellular carcinoma (HCC) for patients with chronic hepatitis B, whether it is associated with the recurrence of HCC after resection remains obscure. This study was aimed to compare the outcomes for patients with minimal or advanced fibrosis in solitary small hepatitis B virus (HBV)-related HCC.Methods
This study enrolled 76 patients with small (<5 cm) solitary HBV-related HCC who underwent resection. The outcomes of patients with minimal and advanced fibrosis in non-tumor areas were compared. Serum markers were tested to assess the stage of hepatic fibrosis and to predict prognosis.Results
Fourteen patients with an Ishak fibrosis score of 0 or 1 were defined as having minimal fibrosis; the remaining 62 patients were defined as having advanced fibrosis. During a follow-up period of 77.0 ± 50.7 months, 41 patients died. The overall survival rate was significantly higher (P = 0.018) and recurrence rate was lower (P = 0.018) for patients in the minimal fibrosis group. Aspartate aminotransferase–platelet ratio index (APRI) exhibited the most reliable discriminative ability for predicting advanced fibrosis. The overall survival rate was significantly higher (P = 0.003) and recurrence rate was lower (P = 0.005) for patients with an APRI of 0.47 or less.Conclusions
For patients with solitary small HBV-related HCC who underwent resection, minimal fibrosis is associated with a lower incidence of recurrence and with better survival. APRI could serve as a reliable marker for assessing hepatic fibrosis and predicting survival. 相似文献5.
Oya Yonal Filiz Akyuz Kadir Demir Sevgi Ciftci Fahriye Keskin Binnur Pinarbasi Ahmet Uyanikoglu Halim Issever Sadakat Ozdil Gungor Boztas Fatih Besisik Sabahattin Kaymakoglu Yilmaz Cakaloglu Zeynel Mungan Atilla Okten 《Digestive diseases and sciences》2010,55(12):3548-3551
Background
Levels of prohepcidin, a homeostatic regulator of iron absorption, are altered in chronic hepatitis C and liver cirrhosis. However, data on the potential alterations of prohepcidin in patients with HBV-related liver disease are scarce. We investigated whether serum prohepcidin is related to iron overload and perenchymal dysfuction in HBV-related liver disease.Methods
Three groups of subjects were studied: 66 patients with chronic hepatitis B, 32 patients with HBV-related cirrhosis, and 42 healthy controls without evidence of liver disease. Serum levels of prohepcidin were determined by enzyme-linked immunosorbent assay.Results
Serum prohepcidin levels were significantly lower in patients with HBV-related cirrhosis (175.85 ± 71.5 ng/ml) than in patients with chronic hepatitis B (209.02 ± 62.7 ng/ml P < 0.05) and controls (222.4 ± 128.4 ng/ml, P < 0.05). After adjustment for potential confounders, prohepcidin was found to be an independent predictor of ferritin levels in multiple linear regression analysis (β = ?1.10, t = ?3.11, P < 0.01).Conclusion
These results demonstrate that prohepcidin levels are reduced in patients with HBV-related cirrhosis and are an independent correlate of serum ferritin. 相似文献6.
Bon Shoji Fusao Ikeda Shin-ichi Fujioka Haruhiko Kobashi Tetsuya Yasunaka Yasuhiro Miyake Hidenori Shiraha Akinobu Takaki Kazuhiro Nouso Yoshiaki Iwasaki Kazuhide Yamamoto 《Journal of gastroenterology》2010,45(11):1172-1182
Background
For patients with chronic hepatitis due to hepatitis B virus (HBV), factors predicting hepatocellular carcinoma (HCC) other than high levels of HBV-DNA and alanine aminotransferase (ALT) are needed to prevent HCC development, as many patients with chronic HBV infection fulfill these conditions. The purpose of this study was to clarify factors predictive of HCC development for those patients.Methods
The study was a systematic cohort analysis of 303 consecutive patients with hepatitis B e-antigen, receiving laparoscopic examination for assessment of liver disease. Laparoscopic, histological, and clinical characteristics were investigated as related to HCC development.Results
HCC occurred in 27 patients during a mean follow-up of 8.0 ± 5.0 years, at the age of 37–72 years. Significant associations with HCC development were shown for liver cirrhosis, histological activity grade, reddish markings, and older age. Multivariate analysis revealed that HCC development was strongly associated with older age and male gender (P = 0.002 and P = 0.043, respectively). HCC occurred more frequently in patients of age ≥30 years even with early stage than in patients of age <30 years (P = 0.031). Severe reddish markings, a laparoscopic finding of widespread parenchymal destruction, were highly associated with HCC development in patients of age ≥30 years at diagnosis (odds ratio = 1.67, P = 0.034), while histological activity grade and ALT level were not (P = 0.075 and P = 0.69, respectively).Conclusions
HCC development is associated with older age, male gender, and liver cirrhosis. Reddish markings, rather than histological activity or ALT level, can be useful to predict HCC for HBV patients of age ≥30 years. 相似文献7.
Monika Sarkar Valentina A. Shvachko Joanna B. Ready Mary Pat Pauly Norah A. Terrault Marion G. Peters M. Michele Manos 《Digestive diseases and sciences》2014,59(9):2100-2108
Background
Few population-based studies have described characteristics and management of patients with chronic hepatitis B (CHB) in the USA.Methods
We retrospectively studied adults with CHB in the Northern California Kaiser Permanente Medical Care Program (KPNC) from July 2009 to December 2010 (n = 12,016). Laboratory tests, treatment patterns, and hepatocellular carcinoma (HCC) surveillance were ascertained during a “recent” 18-month study window (July 2009–December 2010), or as “ever” based on records dating to 1995.Results
The mean age was 49 years; 51 % were men, 83 % Asian, and 87 % KPNC members >5 years. Overall, 51 % had ≥1 liver-related visit, 14 % with gastroenterology or infectious disease specialists, and 37 % with primary care providers (PCP) only. Less than 40 % of patients had both hepatitis B virus (HBV) DNA and ALT testing conducted recently, while 56 % of eligible patients had received HCC surveillance. Recent laboratory testing and HCC surveillance were more frequent in patients seen by a specialist versus PCP only (90 vs. 47 % and 92 vs. 73 %, respectively, p values <0.001). During the study period, 1,649 (14 %) received HBV treatment, while 5 % of untreated patients had evidence of treatment eligibility. Among 599 patients newly initiated on HBV therapy, 76 % had guideline-based indications for treatment.Conclusions
Most patients initiated on HBV treatment met eligibility, and very few patients with evidence of needing treatment were left untreated. However, monitoring of ALT and HBV DNA levels, as well as HCC surveillance, were not frequent, underestimating the proportion of patients that warranted HBV therapy. Viral monitoring and cancer surveillance are therefore important targets for improving the scope of CHB care in the community setting. 相似文献8.
Tan To Cheung Kelvin K. Ng Ronnie T. Poon Sheung Tat Fan 《Journal of hepato-biliary-pancreatic sciences》2009,16(5):655-660
Background
Radiofrequency ablation (RFA) is currently an effective method for ablation of hepatocellular carcinoma (HCC). Early reports have indicated that RFA is safe and virtually free from major complications. Unlike partial hepatectomy for HCC on patients with cirrhosis, there are no data on the safety limit of RFA. However, information is vital for selection of appropriate patients for the procedure. In this study, we analyzed results from use of RFA on HCC patients and determined the lower limit of liver function with which HCC patients can tolerate RFA.Method
Preoperative variables of 310 patients who underwent RFA for HCC were analyzed to identify the risk factors in RFA intolerance in terms of morbidity associated with stress-induced complications.Results
Thirty-nine (12.6%) patients developed intolerance of RFA. Postoperative morbidity was mainly because of intractable ascites (n = 13), hyperbilirubinemia (n = 10), massive pleural effusion (n = 7), and other complications (n = 14). Multivariate analysis revealed that serum albumin level (P = 0.001), serum bilirubin level (P = 0.000), tumor number (P = 0.002), and RFA duration (P = 0.017) all played a role in this issue.Conclusions
Simple data such as serum bilirubin, serum albumin level, and tumor number can be used to predict HCC patients’ tolerance of RFA. Avoidance of excessive RFA time and careful monitoring of patients at risk are important means of reducing the postoperative morbidity rate. 相似文献9.
Makoto Chuma Shuhei Hige Toshiya Kamiyama Takashi Meguro Atsushi Nagasaka Kazuaki Nakanishi Yoshiya Yamamoto Mitsuru Nakanishi Toshihisa Kohara Takuya Sho Keiko Yamamoto Hiromasa Horimoto Tomoe Kobayashi Hideki Yokoo Michiaki Matsushita Satoru Todo Masahiro Asaka 《Journal of gastroenterology》2009,44(9):991-999
Background
Prediction and prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) recurrence is an important clinical issue. We investigated whether HBV DNA level and antiviral therapy are associated with HCC recurrence.Methods
This retrospective study involved 103 patients who underwent hepatic resection or radiofrequency ablation for initial HCC. Patients were divided into four groups. Thirty had high serum HBV DNA levels (>4 log10 copies/mL) and had not received antiviral therapy (high virus group; HVG). Thirty-four had low HBV DNA levels (≤4 log10 copies/mL) and had not received antiviral therapy (low virus group; LVG). Twenty received antiviral therapy after HCC developed (therapeutic group A, TG-A). Nineteen received antiviral therapy before HCC developed (therapeutic group B, TG-B).Results
Cumulative HCC recurrence rates at 3 years in the HVG, LVG, TG-B, and TG-A were 71.1%, 42.2%, 42.3%, and 52.0%, respectively. Recurrence rates differed significantly between the HVG and LVG (P = 0.016) and between the HVG and TG-B (P = 0.008). Recurrence rate in the TG-A was marginally lower than in the HVG (P = 0.10). On multivariate analysis, high serum hepatitis B virus DNA levels (hazard ratio: HR 2.67; 95% CI 1.31–5.47; P = 0.007) and absence of antiviral therapy (HR 2.57; 95% CI 1.34–4.94; P = 0.005) were independent risk factors for hepatocellular carcinoma recurrence.Conclusion
HBV DNA level and antiviral therapy are associated with HCC recurrence. For patients with high HBV DNA levels, antiviral therapy before the development of HCC is important for prevention of recurrence. 相似文献10.
Ji-Dong Jia Jin-Lin Hou You-Kuan Yin De-Ming Tan Daozhen Xu Jun-Qi Niu Xia-Qiu Zhou Yu-Ming Wang Li-Min Zhu Cheng-Wei Chen Yong-Wen He Hong Ren Mo-Bin Wan Shan-Ming Wu Qin-Huan Wang Lai Wei Weibin Bao Yuhong Dong Aldo Trylesinski 《Hepatology International》2014,8(1):72-82
Purpose
The burden of chronic hepatitis B infection is high in China, where prevalence exceeds 7 %. This was a randomized, double-blinded, phase III study of the efficacy and safety of telbivudine and lamivudine treatment at 104 weeks in Chinese patients with chronic hepatitis B.Methods
Hepatitis B e antigen-positive (n = 290) and -negative (n = 42) adults with nucleoside analog–naïve compensated chronic hepatitis B were randomized to receive telbivudine 600 mg/day or lamivudine 100 mg/day for 104 weeks. The primary endpoint was reduction from baseline in serum hepatitis B virus (HBV) DNA at week 52. Week 104 analyses included HBV DNA reductions, undetectable HBV DNA (<300 copies/mL), ALT normalization, and e-antigen loss/seroconversion. Efficacy at week 104 was also assessed as a function of week 24 HBV DNA.Results
In the intention-to-treat population (n = 332) at week 104, telbivudine was superior to lamivudine for reduction of HBV DNA [?5.48 vs. ?4.00 log10 copies/mL; difference ?1.49 log10 (95 % confidence interval ?2.2, ?0.8); p < 0.0001], for the proportion with undetectable HBV DNA (61.9 vs. 38.5 %; p < 0.0001), for ALT normalization (75.8 vs. 61.3 %; p = 0.0049), and for e-antigen loss (39.9 vs. 28.2 %; p = 0.0373). The cumulative probability of genotypic drug resistance was 15.4 % on telbivudine versus 23.6 % on lamivudine through week 104. Early virologic response at week 24 was associated with improved outcomes at week 104. Adverse events were similar to those seen in the GLOBE study.Conclusions
Telbivudine is superior to lamivudine over 2 years of chronic hepatitis B treatment in Chinese patients. 相似文献11.
Pengjun Zhang Xinyu Wen Feng Gu Xinxin Deng Juan Li Jin Dong Jiao Jiao Yaping Tian 《Hepatology International》2013,7(3):893-900
Background
Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). The methylation status of circulating DNA might serve as a potential biomarker for cancers.Methods
Six early stage HCC patients with chronic hepatitis B virus (HBV) infection and six age-matched healthy controls were selected for genome-scale DNA methylation screening of serum by Illumina Infinium Human Methylation 450 BeadChip. The chosen methylation sites were reassessed by bisulfite sequencing in four healthy controls and four early stage HCC patients with chronic HBV infection and were used for bead array screening. Another 27 healthy controls and 31 early stage HCC patients with chronic HBV infection were also chosen for further bisulfite sequencing validation.Results
Whole-genome methylation was significantly lower in serum from HCC patients than in that from healthy controls. After bioinformatics analysis, methylation at DBX2 and Thy-1 membrane glycoprotein (THY1) was reassessed by bisulfite sequencing. The correlation coefficients of DBX2 and THY1 between the Illumina 450 BeadChip and bisulfite sequencing were respectively 0.9145 and 0.8232. Twenty-seven healthy controls and 31 early stage HCC patients with chronic HBV infection were chosen for further validation. The diagnostic sensitivity and specificity of DBX2 for differentiating healthy controls and early stage HCC were 88.89 and 87.10 % and of THY1 were 85.19 and 80.65 %.Conclusions
The results demonstrated that the 450K BeadChip is a useful tool for whole-genome serum DNA methylation screening of HCC, and some HCC-related DNA methylation sites were screened. 相似文献12.
Wai-Kay Seto Danny Ka-Ho Wong James Fung Ivan Fan-Ngai Hung John Chi-Hang Yuen Teresa Tong Ching-Lung Lai Man-Fung Yuen 《Hepatology International》2013,7(1):119-126
Background
We investigated the differences in HBsAg kinetics at different levels of viremia in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB).Methods
We compared HBsAg levels among HBeAg-negative CHB patients with persistently undetectable HBV DNA (≤20 IU/mL; Group A, n = 100), HBV DNA 20–2,000 IU/mL (Group B, n = 100), and HBV DNA >2,000 IU/mL (Group C, n = 100). HBsAg and HBV DNA levels were measured at three consecutive time points during follow-up (median 21.4 months).Results
Median HBsAg levels were significantly lower in Group A than in Groups B and C at all time points (p < 0.001). HBV DNA and HBsAg levels were weakly correlated (r = 0.180 and 0.151 for Groups B and C, respectively). Among patients with HBsAg <100 IU/mL, Group A patients had the greatest median serum HBsAg reduction (0.341 log IU/mL/year; Group B, 0.122 log IU/mL/year; Group C, 0.057 log IU/mL/year; p = 0.002). Among Group A patients with HBsAg <100 IU/mL, baseline HBsAg achieved an AUROC of 0.876 in predicting >1 log annual HBsAg reduction; 10–100 IU/mL HBsAg was the optimal level for prediction (sensitivity 90 %; specificity 74.6 %). Serum HBsAg/HBV DNA ratios were significantly higher in Group B than in Groups A and C (p < 0.05).Conclusions
HBV DNA and HBsAg were weakly correlated. Only patients with undetectable HBV DNA showed decline in HBsAg levels during follow-up. The greatest reduction in HBsAg levels occurred in patients with baseline HBsAg <100 IU/mL. 相似文献13.
Xiangyu Kong Yiqi Du Guokun Wang Jun Gao Yanfang Gong Lei Li Zhuo Zhang Jiaqi Zhu Qing Jing Yongwen Qin Zhaoshen Li 《Digestive diseases and sciences》2011,56(2):602-609
Background
MicroRNAs (miRNAs) have long been established to remain stable in circulation, and dysregulated miRNAs in serum of tumor patients could potentially serve as novel biomarkers.Aims
To determine whether certain serum miRNAs could represent potential diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC).Methods
About 35 patients diagnosed with PDAC at different stages between August 2007 and January 2009 were enrolled in this study. Sera from 15 chronic pancreatitis (CP) patients and 15 healthy individuals were treated as controls. Quantitative real-time polymerase chain reaction assays specific to mature miRNAs were used to quantify the relative levels of those PDAC-associated serum miRNAs.Results
Of the seven miRNAs detected, three were identified as differentially expressed in PDAC and control groups. miR-21 was able to distinguish PDAC patients from CP (p = 0.033) and healthy subjects (p = 0.001), whereas miR-155 and miR-196a were able to differentiate sera with sick pancreas (PDAC/CP) from normal pancreas (p = 0.0002 and 0.010, respectively). Serum miR-196a expression levels in unresectable PDAC (stages III and IV) patients were significantly higher than those in resectable (stages I and II) patients (p = 0.001). Furthermore, serum miR-196a expression level was found to have a potential value in predicting median survival time of PDAC patients (high-level miR-196a, 6.1 months, (95% CI, 4.49?C7.72) versus low-level miR-196a, 12.00 months, (95% CI, 5.92?C18.08), p = 0.007).Conclusions
Serum miR-196a could be a potential noninvasive marker for PDAC prognosis and selection of laparotomy. 相似文献14.
Yasuto Takeuchi Fusao Ikeda Yuki Moritou Hiroaki Hagihara Tetsuya Yasunaka Kenji Kuwaki Yasuhiro Miyake Hideki Ohnishi Shinichiro Nakamura Hidenori Shiraha Akinobu Takaki Yoshiaki Iwasaki Kazuhiro Nouso Kazuhide Yamamoto 《Journal of gastroenterology》2013,48(3):405-412
Background
The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases.Methods
We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC).Results
NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P < 0.001 and <0.001, respectively; log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P < 0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028).Conclusions
The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients. 相似文献15.
Sen Yang Hong-Li Yan Qi-Fei Tao Sheng-Xian Yuan Guan-Nan Tang Yuan Yang Li-Li Wang Yi-Liang Zhang Shu-Han Sun Wei-Ping Zhou 《Journal of cancer research and clinical oncology》2014,140(1):109-116
Purpose
To investigate the expression and clinical significance of CADM2 in hepatocellular carcinomas (HCC).Methods
The level of expression of CADM2 mRNA was assessed in frozen tumor specimens and adjacent noncancerous tissues from 30 HCC patients by real-time PCR. The protein level was determined by immunohistochemistry on a tissue microarray containing tumor and adjacent noncancerous tissues from 234 HCC patients. Clinicopathological characteristics associated analysis was performed through SPSS18 .Results
CADM2 was strikingly down regulated in HCC. CADM2 expression was associated with differentiation (P = 0.000), serum alpha-fetoprotein (P = 0.003), vascular invasion (P = 0.001), and hepatitis B surface antigen (HBsAg, P = 0.038). Furthermore, patients with low CADM2 expression had significantly poorer recurrence-free survival (RFS) (40.8 and 34.2 % vs. 56.3 and 50.1 % in 3- and 5-year RFS, respectively, P = 0.005). Subgroup analysis revealed that the difference in RFS between groups with low- and high-CADM2 expression still existed among patients belonging to stage 0 or A of BCLC staging system (P = 0.008), patients with tumor ≤5 cm in size (P = 0.013), and alpha-fetoprotein-negative patients (P = 0.003). Moreover, low expression was more frequently observed in the early recurrence group (within 2 years, P = 0.007). Further multivariate Cox regression analysis indicated that CADM2 expression level, tumor size, tumor number, vascular invasion, HBsAg were independent risk factors for HCC recurrence.Conclusion
CADM2 serves as a novel predictor of RFS in HCC patients after curative resection. 相似文献16.
Myron John Tong Thatcher Thi Huynh Surachate Siripongsakun 《Hepatology International》2013,7(4):1019-1029
Purpose
The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated.Methods
Four hundred thirteen HBsAg-positive patients, 173 with HCC and 240 without HCC, were subgrouped into those with or without a family history of HCC and analyzed for risk factors associated with HCC development. In families with HCC clustering, the ages of HCC onset in parents and siblings were compared.Results
Forty-four of 173 (25.4 %) HCC patients, all of Asian descent, had 82 other blood relatives with HCC. Of these, 69 (84.1 %) were first-degree relatives. Compared to HCC patients without HCC family history, male HCC patients with family history developed HCC at a younger age than either their mothers or fathers with HCC (45.2 ± 10.3 years vs. 63.0 ± 6.8 years, p < 0.001 and 41.2 ± 14.8 years vs. 60.5 ± 5.5 years, p = 0.001, respectively); however, this was not observed in female HCC patients. In mothers of index HCC cases, 22/26 (84.6 %) tested were HBsAg positive and 14 (63.6 %) had HCC; in fathers, 11/21 (52.4 %) tested were HBsAg positive and 10 (90.9 %) had HCC. By multivariate analysis, independent risk factors for HCC development included family history (OR = 2.58, p = 0.05), male gender (OR = 3.23, p = 0.03), cirrhosis (OR = 2.4, p = 0.04), Child-Pugh classification (OR = 7.62, p = 0.004), AFP per log10 increase (OR = 1.68, p = 0.01), precore mutation (OR = 3.77, p = 0.003), and basal core promoter mutation (OR = 8.33, p < 0.001).Conclusions
HBsAg-positive male HCC patients presented at a younger age than their parents with HCC. In adult patients with an HCC family history, HCC surveillance should begin at the time of the initial clinic encounter. 相似文献17.
Masataka Tsuge Eisuke Murakami Michio Imamura Hiromi Abe Daiki Miki Nobuhiko Hiraga Shoichi Takahashi Hidenori Ochi C. Nelson Hayes Hiroyuki Ginba Kazuhiro Matsuyama Hiroiku Kawakami Kazuaki Chayama 《Journal of gastroenterology》2013,48(10):1188-1204
Background
Treatment for chronic hepatitis B has improved drastically with the use of nucleot(s)ide analogues (NAs). However, NA therapy typically fails to eliminate Hepatitis B virus (HBV) completely, and it is difficult to discontinue these therapies. We previously demonstrated that NA therapy induced immature viral particles, including HBV RNA in sera of chronic hepatitis B patients. In the study reported here, we analyzed the association between HBV RNA titer and the recurrence rate of hepatitis after discontinuation of NA therapy.Methods
The study cohort comprised 36 patients who had discontinued NA therapy. Serum HBV DNA or DNA plus RNA levels were measured by real time PCR and statistical analyses were performed using clinical data and HBV markers.Results
At 24 weeks after discontinuation of NA therapy, HBV DNA rebound was observed in 19 of the 36 patients (52.8 %), and alanine aminotransferase (ALT) rebound was observed in 12 of 36 patients (33.3 %). Multivariate statistical analysis was used to identify factors predictive of HBV DNA rebound. The HBV DNA + RNA titer following 3 months of treatment was significantly associated with HBV DNA rebound [P = 0.043, odds ratio (OR) 9.474, 95 % confidence interval (CI) 1.069–83.957)]. Absence of hepatitis B e antigen (HBeAg) at the end of treatment was significantly associated with ALT rebound (P = 0.003, OR 13.500, 95 % CI 2.473–73.705). In HBeAg-positive patients, the HBV DNA + RNA titer after 3 months of treatment was marginally associated with ALT rebound (P = 0.050, OR 8.032, 95 % CI 0.997–64.683).Conclusions
Monitoring of serum HBV DNA + RNA levels may be a useful method for predicting re-activation of chronic hepatitis B after discontinuation of NA therapy. 相似文献18.
Chung GE Kim W Lee KL Hwang SY Lee JH Kim HY Jung YJ Kim D Jeong JB Kim BG Kim YJ Yoon JH Lee HS 《Digestive diseases and sciences》2011,56(7):2130-2136
Background/Aims
Lamivudine (LAM) has been extensively used to treat hepatitis B, but high incidence of drug resistance has required rescue studies. We validated the optimum treatment strategy for LAM-resistant patients by means of a comparative study of add-on adefovir (ADV) and a switch to entecavir (ETV).Methods
We assessed the virologic response in consecutive LAM-resistant patients who received add-on ADV or a switch to ETV.Results
The mean reduction of serum hepatitis B virus (HBV) DNA levels was significantly less in the ETV group than in the add-on ADV group (?3.45 vs. ?4.17; P = 0.047 at week 24 and ?3.81 vs. ?4.68 log10 IU/mL; P = 0.044 at week 48). Achievement of undetectable HBV DNA was significantly lower in the ETV group than in the add-on ADV group (P = 0.043). Multivariate analysis showed that add-on ADV, baseline HBV DNA levels, and initial virologic response were significant predictors of HBV DNA negativity (adjusted OR, 2.582; P = 0.008, 0.304; P = 0.001, and 5.928; P = 0.001). Virologic breakthrough was observed for 12 patients, in the ETV group only.Conclusions
Add-on ADV was more effective and durable than ETV as rescue therapy. Therefore, add-on ADV might be the preferred strategy for LAM-resistant patients who need long-term antiviral treatment. 相似文献19.
Dong Hyun Sinn Moon Seok Choi Geum-Youn Gwak Yong-Han Paik Joon Hyeok Lee Kwang Cheol Koh Seung Woon Paik Byung Chul Yoo 《Digestive diseases and sciences》2013,58(3):751-758
Background
Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC).Aims
We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way.Methods
A total of 195 patients with chronic HBV infection [age: 43.7 ± 10.8 years, males: 141 (72.3 %), genotype C: 195 (100 %), hepatitis B e antigen (HBeAg) positive: 109 (55.9 %), cirrhosis: 79 (40.5 %), and pre-S mutation positive: 44 (22.6 %)] were followed up for a median of 7.2 years (range 1.0–7.8 years).Results
HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4 %, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7 %, p < 0.001) and showed higher hazard ratio for HCC [3.04 (95 % CI 1.24–7.42), p = 0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged ≥50 years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3 %), compared to those without (16.1 %, p < 0.001).Conclusions
Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development. 相似文献20.
Jia-Feng Wu Wen-Yu Tsai Yi-Ching Tung Huey-Ling Chen Yen-Hsuan Ni Hong-Yuan Hsu Mei-Hwei Chang 《Journal of gastroenterology》2014,49(5):900-906