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ABSTRACT: BACKGROUND AND AIM: In cases of small hepatocellular carcinoma (HCC) where established curative treatment cannot be applied, stereotactic body radiotherapy (SBRT) has been used as a non-invasive alternative treatment modality. However, short-course SBRT may not be safe if the tumor is located around a critical normal organ. Therefore, we applied hypofractionated radiotherapy for these tumors, and evaluated outcomes of this treatment. METHODS: Between December 2008 and August 2011, 26 patients (28 lesions) with HCC were treated with hypofractionated radiotherapy. Inclusion criteria were HCC not suitable for surgery or other local ablative therapy, a tumor size < 6 cm, adequate hepatic function, a HCC located within 2 cm of a critical organ, and no evidence of vascular invasion. A dose of 4-5 Gy per fraction was given, with a total dose of 40-50 Gy over two weeks. RESULTS: The overall response rate was 67.9%, with 7 complete responses (25.0%) and 12 partial responses (42.9%) at 3 months after radiotherapy. The overall survival rates at 1 and 2 years were 88.5% and 67.2%, respectively. The local control rate at 2 years was 87.6%. The Intrahepatic recurrence-free and distant failure-free survival rates at 2 years were 36.5% and 68.2%, respectively. Grade ≥ 3 hepatic toxicity was observed in 1 patient. CONCLUSIONS: Two-week schedule of hypofractionated radiotherapy for small HCC was feasible with good local control and safety. This fractionation schedule can be used as an alternative treatment option for HCC located close to a critical normal organ if short-course SBRT is not feasible.
Journal of Gastroenterology and Hepatology 04/2013; · 2.87 Impact Factor
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Nae-Yun Heo,
Young-Suk Lim,
Han Chu Lee,
Yung Sang Lee, Kang Mo Kim,
Kwan Soo Byun,
Kwang-Hyub Han,
Kwan Sik Lee,
Seung Woon Paik,
Seung Kew Yoon,
Dong Jin Suh
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ABSTRACT: Identifying the impact of a patient's ethnicity on treatment responses in clinical practice may assist in providing individualized treatment regimens for chronic hepatitis C (CHC). The effectiveness of standard peginterferon plus ribavirin therapy and the need for triple combination therapy with protease inhibitors in Koreans remain matters of debate. These issues were investigated in the present study.
The clinical data of 272 treatment-naïve Korean CHC patients who were treated in a community-based clinical trial (Clinical Trial group; n=51) and in clinical practice (Cohort group; n=221), were analyzed and compared. All were treated with standard protocols of peginterferon alfa-2a plus ribavirin therapy.
For patients with hepatitis C virus (HCV) genotype 1, the sustained virological response (SVR) rates in the Clinical Trial and Cohort groups were 81% (21/26) and 55% (58/106), respectively, by intention-to-treat (ITT) analysis (P=0.02), and 100% (13/13) and 80% (32/40), respectively, in treatment-adherent patients (P=0.18). For patients with HCV genotype 2, the SVR rates in these two groups were 96% (24/25) and 88% (101/115), respectively, by ITT analysis (P=0.31). Adherence and treatment duration were independent predictors of SVR for genotypes 1 and 2, respectively (P<0.01 for each). Korean patients with CHC achieved high SVR rates with peginterferon alfa-2a plus ribavirin in both the clinical trial and clinical practice settings.
Measures to raise adherence to standard therapy in clinical practice may improve the SVR rates in these patients as effectively as adding protease inhibitors, thus obviating the need for the latter.
Clinical and molecular hepatology. 03/2013; 19(1):60-69.
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Young-Joo Jin,
Young-Hwa Chung,
Jeong A Kim,
Wonhyeong Park,
Don Lee,
Ju Hyun Shim,
Danbi Lee, Kang Mo Kim,
Young-Suk Lim,
Han Chu Lee,
Yung Sang Lee,
Pyo Nyun Kim,
Kyu Bo Sung
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ABSTRACT: BACKGROUND AND AIM: The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE). METHODS: A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time. RESULTS: Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥60 years; HR 1.531, P = 0.043), advanced Child-Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR. CONCLUSIONS: Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver.
Digestive Diseases and Sciences 01/2013; · 2.12 Impact Factor
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Wonhyeong Park,
Young-Hwa Chung,
Jeong A Kim,
Young-Joo Jin,
Don Lee,
Ju Hyun Shim,
Danbi Lee, Kang Mo Kim,
Young-Suk Lim,
Han Chu Lee,
Yung Sang Lee,
Pyo Nyun Kim,
Kyu Bo Sung
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ABSTRACT: AIM: In this study, we analyzed the rates and patterns of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE) or radiofrequency ablation (RFA), and also examined the differences of recurrence patterns between TACE-treated and RFA-treated groups. METHODS: We followed 309 consecutive HCC patients who achieved CR following TACE (n = 220) or RFA (n = 89) for a median of 68 months. Recurrence patterns were classified as local recurrence and secondary tumor according to location of recurrence (≤2 cm and >2 cm from primary tumor). RESULTS: Recurred HCC had been found in 231 out of 309 patients (75%) with CR by TACE or RFA; 112 local recurrences (48%), 100 secondary tumor (43%) and 19 both (9%). The cumulative recurrence rates at 1, 3 and 5 years were 22%, 64% and 79%, respectively. The overall recurrences at 1, 3 and 5 years following CR in the TACE-treated group was not different from those in the RFA-treated group (21%, 68% and 81% vs 26%, 56% and 84%, respectively; P = NS) However, the cumulative occurrence rates of local recurrence rates at 1, 3 and 5 years were significantly higher in the TACE-treated group compared to the RFA-treated group (15%, 53% and 65% vs 15%, 27% and 34%, respectively; P = 0.001). CONCLUSION: Recurrence of HCC is very common, even following CR by TACE or RFA. Especially, local recurrences are very frequent in cases who achieved CR by TACE, which suggests that additional ablation therapy may be beneficial to prevent recurrences following CR by TACE.
Hepatology Research 01/2013; · 2.20 Impact Factor
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ABSTRACT: PURPOSE: To determine the usefulness of enhancement by iodized oil deposits on computed tomography (CT) following transarterial chemoembolization for hepatocellular carcinoma (HCC), and to compare the reliability of such CT imaging with that of magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifty-one patients for whom resected or explanted livers containing chemoembolized HCC lesions of at least 1 cm were available. Imaging responses were determined based on modified Response Evaluation Criteria In Solid Tumors (mRECIST) and European Association for the Study of the Liver (EASL) criteria for 59 target tumors on CT and MR scans before surgery. CT-based evaluation was performed per mRECIST and EASL criteria, considering iodized oil retention as indicating necrosis and, alternatively, as enhancing viable tissue ("mRECIST-Lipiodol" and "EASL-Lipiodol"). Pathologic necrosis was graded as 100%, 50%-99%, or less than 50%. RESULTS: Goodman-Kruskal γ-values for radiologic-pathologic correlation were greater than 0.95 for mRECIST and EASL criteria on CT or MR imaging. However, mRECIST-Lipiodol and EASL-Lipiodol measurements showed weaker correlation with pathologic findings, with γ-values of 0.797 and 0.846, respectively. With respect to intermethod agreement, weighted γ-values for mRECIST by CT and MR, and for EASL criteria by CT and MR, both exceeded 0.80, whereas mRECIST-Lipiodol and EASL-Lipiodol showed only moderate levels of agreement with mRECIST/EASL criteria by CT or MR imaging, with γ-values of 0.522-0.631. CONCLUSIONS: Response estimation based on measurement of iodized oil deposits as necrosis on CT when applying enhancement criteria after chemoembolization for HCC correlated well with actual pathologic class, and agreed with MR-based evaluation.
Journal of vascular and interventional radiology: JVIR 01/2013; · 1.81 Impact Factor
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ABSTRACT: Pre-S mutation of hepatitis B virus (HBV) is known to be a risk factor for hepatocarcinogenesis. A previous study suggested that pre-S mutation(s) may associate with increased recurrence after surgical resection. In the present study, 64 patients with HBV-related hepatocellular carcinoma (HCC) were categorized into two groups according to the presence or absence of pre-S mutation(s). The clinicopathological variables of the two groups were analyzed to assess the relationship between pre-S mutations and postoperative recurrence. Nineteen patients (29.7%) had pre-S mutations;13 had a pre-S deletion, three had a pre-S2 start codon mutation, two patients had both a pre-S deletion, and a pre-S2 start codon mutation, and one patient had a pre-S2 insertion. The two groups did not differ in terms of baseline clinicopathological parameters. Cirrhosis and satellite lesion(s) were predictive factors for postoperative recurrence and poor overall survival. Recurrence-free survival (P = 0.320) and overall survival (P = 0.238) did not differ significantly when pre-S mutations were present. In conclusion, this study did not find evidence supporting the notion that pre-S mutation(s) are associated with postoperative recurrence after surgical resection. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
Journal of Medical Virology 01/2013; · 2.82 Impact Factor
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ABSTRACT: OBJECTIVE:: To explore the prognostic value of the postsurgical half-life (HL) of serum alpha-fetoprotein (AFP). BACKGROUND:: There is still a paucity of early surrogate indicators of clinical endpoints after liver resection of hepatocellular carcinoma (HCC). METHODS:: The analysis was based on cohorts of 225 (exploration set) and 117 (validation set) treatment-naïve HCC patients undergoing curative liver resection. We defined 3 categories of AFP HL: early complete resolution of AFP, normal HL, and prolonged HL if the HL exceeded 7 days. Overall, probabilities of recurrence and survival were estimated and compared across the AFP HL categories. RESULTS:: In the exploration cohort, 48 patients (21.3%) achieved early AFP complete resolution, 116 (51.6%) had normal HL, and 61 (27.1%) had prolonged HL. Long AFP HL was significantly associated with early postoperative recurrence (P < 0.001), as was microvascular invasion. Early recurrence within 2 years of resection was observed in 59% of the patients with prolonged AFP HL compared with only 29.3% of those with normal AFP HL (P < 0.001). A log-rank test followed by multivariate Cox analysis identified an independent function of prolonged AFP HL in predicting shorter recurrence-free survival and overall survival time after HCC resection (hazard ratios, 2.81 and 3.58; P < 0.001). When AFP HL analysis was applied to the validation cohort, the association between prolonged AFP HL and survival endpoints (hazard ratio, 11.63 and 16.39; P < 0.001) was confirmed.
Annals of surgery 10/2012; · 7.90 Impact Factor
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ABSTRACT: Background/aimsLittle is known about the long-term outcome of chronic hepatitis B (CHB) patients who discontinued antiviral therapy. We intended to analyze the long-term outcome of CHB patients who discontinued lamivudine therapy and to evaluate predictors for post-treatment outcome.Material/methodsFrom 2007 to 2008, 138 lamivudine off-treated CHB patients with alanine aminotransferase normalization were consecutively enrolled. Post-treatment virologic relapse, biochemical breakthrough, hepatitis flare, and retreatment results were retrospectively analyzed. RESULTS: Among 138 patients, 102 were initially HBeAg-positive at the start of lamivudine treatment. Virologic relapse, biochemical breakthrough, and hepatitis flare were observed in 45.2, 52.9, and 12.7% of HBeAg-positive and 29.4, 30.6, and 8.3% of HBeAg-negative patients during the median follow-up of 28 and 30 months, respectively. The cumulative virologic relapse and biochemical breakthrough rates were significantly lower in patients with HBV DNA <50 copies/mL than 50-104 copies/mL at lamivudine cessation. Hepatitis flare was observed in 4.8 and 11.8% of HBeAg-positive and HBeAg-negative patients with HBV DNA <50copies/mL, respectively. Thirty-eight among 138 patients received retreatment and most of them achieved biochemical (37/38) and virologic response (35/38) within 1 year of retreatment. Undetectable serum HBV DNA (<50 copies/mL) and young age at lamivudine cessation were inversely associated with virologic relapse. Undetectable HBV DNA at cessation, female, and initial HBeAg-negative were inversely associated with biochemical breakthrough. CONCLUSIONS: Post-treatment virologic relapse and biochemical breakthrough incidence were low in patients who achieved undetectable viral titer at lamivudine cessation. Retreatment after biochemical breakthrough or virologic relapse was safe and effective. Intermittent antiviral therapy might be cautiously considered in appropriately selected CHB patients.
Virology Journal 10/2012; 9(1):239. · 2.34 Impact Factor
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ABSTRACT: Serum alpha-fetoprotein (AFP) is frequently used to predict posthepatectomy outcomes in patients with hepatocellular carcinoma (HCC), but its predictive value is still not established. Therefore, we assessed the prognostic significance of AFP status.
Of 525 patients undergoing curative hepatectomy for HCC, 290 had preoperative AFP levels of ≥20 ng/mL (AFP-positive group) and 235 had AFP levels of <20 ng/mL (AFP-negative group). We compared the 2 groups with respect to time-to-recurrence, using the inverse probability of treatment weighted (IPTW) for the entire cohort and propensity score matching, and the cumulative incidence of HCC-specific mortality using competing risks regression.
During follow-up (median duration 64 months, range 2-137 months), HCC recurred in 54.9 % of the AFP-negative group and 52.4 % of the AFP-positive group; there was no death without recurrence. After IPTW adjustment, time-to-recurrence did not differ in the 2 groups (hazard ratio [HR] 0.86, 95 % confidence interval [95 % CI] 0.66-1.12; P = 0.28). In a propensity-score matched cohort (152 pairs), time-to-recurrence data were similar to those obtained by IPTW adjustment (HR 0.91, 95 % CI 0.65-1.25; P = 0.55). There was no difference in recurrence pattern (site and stage) or treatment between the 2 groups even after propensity-score matching. The adjusted HR evaluating the impact of AFP positivity on the risk of HCC-specific mortality was 0.77 (95 % CI 0.54-1.08; P = 0.13) A multivariable competing risks analysis also failed to reveal a significant correlation between baseline AFP level and HCC-specific mortality in the AFP-positive group.
Preoperative AFP levels are not useful for predicting recurrence or survival endpoints following curative hepatectomy for HCC.
Annals of Surgical Oncology 05/2012; 19(12):3687-96. · 4.17 Impact Factor
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ABSTRACT: Serial α-fetoprotein (AFP) measurements are useful for assessing tumor responses to numerous therapies for hepatocellular carcinoma (HCC). This study tested the predictive value of changes in des-γ-carboxy prothrombin (DCP), in parallel with AFP, as an indicator of HCC response after transarterial chemoembolization.
The study group consisted of 327 patients with HCC initially seropositive for DCP (≥ 40 mAU/mL) and/or AFP (≥ 100 ng/mL) who underwent repeated chemoembolization as first-line therapy. Radiologic responses were measured based on modified Response Evaluation Criteria In Solid Tumors guidelines. Serologic response was defined as a decrease of at least 50% in DCP or AFP level from baseline. Radiologic-serologic correlation and disease progression and survival according to serologic responses were analyzed.
Before treatment, 129 patients (39%) had high DCP alone, 66 (20%) had high AFP alone, and 58 (18%) had high levels of both. Radiologic and serologic responses were achieved in 88.2% and 91.4% of patients with high DCP levels and in 89.5% and 91.1% of those with high AFP levels, respectively. Serologic response based on AFP or DCP was significantly correlated with radiologic response, and this was confirmed by landmark analysis (P < .001). DCP and AFP responders had better times to progression and overall survival than nonresponders (P < .001). Cox models revealed that both serologic responses were independent estimates of survival (hazard ratios, 0.11 for DCP and 0.14 for AFP; P < .001).
After transarterial chemoembolization for HCC, DCP response may be a useful surrogate endpoint of immediate and prolonged clinical outcomes, along with AFP response.
Journal of vascular and interventional radiology: JVIR 05/2012; 23(7):927-36. · 1.81 Impact Factor
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Young-Joo Jin, Kang Mo Kim,
Shin Hwang,
Sung Gyu Lee,
Tae-Yong Ha,
Gi-Won Song,
Dong-Hwan Jung,
Ki-Hun Kim,
Eunsil Yu,
Ju Hyun Shim,
Young-Suk Lim,
Han Chu Lee,
Young-Hwa Chung,
YungSang Lee,
Dong-Jin Suh
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ABSTRACT: We evaluated efficacy of exercise and diet modification for steatosis improvement of non-obese non-alcoholic fatty liver disease (NAFLD) patients.
We analyzed retrospectively the clinical and histological parameters of consecutive living liver donors, who experienced repeated liver biopsies due to steatosis and were treated using exercise and diet modification.
From 1995 to 2009, among a total of 1365 potential living liver donors with NAFLD seen on the initial liver biopsy, 120 consecutive donors with steatosis ≥ 30% or an estimated donor-recipient weight ratio < 0.8, underwent exercise and diet modification and received follow-up liver biopsy at our institution. Median age was 33 years, and median interval between the two consecutive biopsies was 10 weeks (range, 1-39). At the time of initial biopsy, the number of normal body mass index, overweight, and obese donors was 49 (40.8%), 65 (54.2%), and 6 (5.0%), respectively. After lifestyle modification, weight reduction and steatosis improvement were observed in 92 (76.7%) and 103 (85.8%) donors, respectively, at the time of follow-up biopsy. On multivariate analysis, initially higher steatosis (hazard ratio [HR] 1.03, P = 0.02), total cholesterol reduction ≥ 10% (HR 5.59, P = 0.02), and weight reduction ≥ 5% (HR 6.63, P = 0.03) were significantly associated with ≥ 20% steatosis improvement in 120 donors with NAFLD, after exercise and diet modification.
Exercise and diet modification were effective in reducing steatosis in potential living liver donors with non-obese NAFLD. Total cholesterol reduction ≥ 10% could be used as a non-invasive predictor for steatosis improvement in liver donors with NAFLD, after exercise and diet modification.
Journal of Gastroenterology and Hepatology 05/2012; 27(8):1341-7. · 2.87 Impact Factor
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Ki Hun Kim,
Sung Gyu Lee,
Eun Hwa Park,
Shin Hwang,
Chul Soo Ahn,
Deok Bog Moon,
Tae Yong Ha,
Gi Won Song,
Dong Hwan Jung, Kang Mo Kim,
Young Suk Lim,
Han Chu Lee,
Young Hwa Chung,
Yung Sang Lee,
Dong Jin Suh
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ABSTRACT: BackgroundCombined hepatocellular carcinoma and cholangiocarcinoma is a very rare form of primary liver cancer containing components
of both tumor types. We evaluated the effectiveness of surgical treatment and factors related to survival and recurrence.
Patients and MethodsOf the 2427 patients who underwent hepatectomy or liver transplantation because of a primary hepatic malignancy from January
1989 to July 2006 at the Asan Medical Center, Seoul, Korea, 29 had hepatocellular carcinoma and cholangiocarcinoma as a single
mixed or transitional tumor. Their medical records were retrospectively reviewed.
ResultsDisease-free survival rates at 6months, 1year, and 3years were 51.1%, 38.3%, and 25.6%, respectively. Univariate analysis
showed that CA 19–9 above 37U/ml was predictive of low overall survival (P=.03) and that TNM stage was significantly associated with disease-free survival (P=.04).
ConclusionsPatients with combined hepatocellular carcinoma and cholangiocarcinoma had poor postoperative survival rates. High CA 19–9
level was associated with poorer survival, suggesting that the cholangiocarcinoma portion may be a major determining factor
for patient prognosis. Aggressive surgical treatment, including lymph node dissection, may improve survival in patients suspected
of or diagnosed with these tumors.
Annals of Surgical Oncology 04/2012; 16(3):623-629. · 4.17 Impact Factor
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ABSTRACT: Although sorafenib has shown survival benefits in patients with hepatocellular carcinoma (HCC), many patients require discontinuation or dose reduction due to adverse events (AEs). We applied a dose escalation scheme to increase patient compliance and avoid AEs.
Of 267 HCC patients treated with first-line sorafenib, 25 at increased risk of AEs, including those with advanced liver cirrhosis, a history of liver transplantation, or cytopenia, received the dose escalation scheme. They started on a reduced dose of sorafenib which increased to the standard dosage according to tolerance in each patient. We analyzed the efficacy and safety of the dose escalation scheme.
Patients with risk factors showed a lower disease control rate, shorter survival, and more frequently grade 3/4 AEs. Among patients presenting risk factors, the dose scheme did not affect the efficacy of sorafenib or survival, but reduced the incidence of grade 3/4 AEs. Rates of sorafenib discontinuation and dose reduction related to AEs were also lower in the dose escalation group. Dose escalation to the standard dose of sorafenib was achieved in 16 of the 25 patients in the dose escalation group (64.0%). After 2 weeks, the dose intensity of sorafenib did not differ between the two dose schemes.
The sorafenib dose escalation scheme may increase patient compliance and tolerance to prolonged treatment, thus enhancing the efficacy of sorafenib in patients at high risk of AEs or with poor tolerance. Further prospective analyses are needed to determine the usefulness of the dose escalation scheme.
Oncology 02/2012; 82(2):119-25. · 2.27 Impact Factor
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ABSTRACT: The value of chest computed tomography (CT) and bone scan (BS) during initial staging workup for hepatocellular carcinoma (HCC) patients has not been evaluated in a large patient group.
A prospective cohort of 381 patients who were initially diagnosed as having HCC at our institution between 2008 and 2010 was enrolled. We evaluated whether chest CT and BS could affect Barcelona Clinic Liver Cancer (BCLC) and Union for International Cancer Control (UICC) (7th) staging, compared with liver dynamic CT (LDCT) and chest X-ray.
Abnormal findings on chest CT and BS were observed in 59.6% and 52.8% of 381 patients, respectively. Thirty and eight patients, respectively, had truly metastatic intrathoracic and bone lesions, with 19 (49.8%) and 7 (87.5%) exhibiting the same lesions on LDCT or chest X-ray. Of the 381 patients, 60 (15.7%), 134 (35.2%), 61 (16.0%), 119 (31.2%), and 7 (1.8%) had BCLC stages 0, A, B, C, and D, respectively; 176 (46.2%), 83 (21.8%), 41 (10.8%), 39 (10.2%), 0 (0%), 8 (2.1%), and 34 (8.9%) had UICC stages I, II, IIIA, IIIB, IIIC, IVA, and IVB, respectively before chest CT and BS. Only three of 381 patients showed a shift in BCLC stage [B→C (3/61, 4.9%)]. Chest CT and BS revealed additional metastases in only 1.1%, 14.0%, and 5.6% of patients with UICC stage T2, T3a, and T3b, respectively.
Chest CT and BS do not provide additional information on metastasis in HCC patients with BCLC 0, A, C, or D stages, and UICC T1 or T4 stages on LDCT.
Journal of Hepatology 02/2012; 56(6):1324-9. · 9.26 Impact Factor
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ABSTRACT: Objectives: The aim of this study was to examine whether interferon-α (IFN-α) therapy may reduce the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) and to determine its effect based on responsiveness to IFN-α therapy. Methods: A total of 641 biopsy-proven CHB patients were treated with IFN-α2b. They were followed by biochemistry and/or imaging studies at 3- to 6-month intervals for a median period of 113 months (range 6-222). Results: HCC was detected in 22 patients and 5- and 10-year cumulative occurrence rates were 0.4 and 3.2%, respectively. In univariate analysis, age (p < 0.001), serum AFP levels (p < 0.001), and serum HBV-DNA levels (p = 0.002) at baseline were associated with HCC development. HCC occurred less frequently in biochemical responders at the end of treatment than in non-responders (p = 0.001). However, virologic response was not associated with HCC development. Multivariate analysis showed that poor biochemical response (p = 0.007) as well as older age (p = 0.018) and a higher serum AFP level (p < 0.001) remained independent predisposing factors of HCC development in CHB patients treated with IFN-α. Conclusion: The results suggest that the biochemical but not virologic response to IFN-α therapy reduces independently the occurrence of HCC in patients with CHB.
Digestive Diseases 01/2012; 30(6):568-73. · 2.37 Impact Factor
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ABSTRACT: Objective: The associations between arrest-defective protein 1 (ARD1) gene expression and the clinicopathological characteristics and clinical outcomes of 94 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) were investigated. Methods: ARD1 mRNA levels in HCC and corresponding non-cancerous tissues were quantified by real-time PCR. The gene expression of the tumor relative to that in the non-tumor tissues was calculated using the 2(-)(ΔΔ)(CT) method. The subjects were classified into high expression (2(-)(ΔΔ)(CT) > 1, n = 38) and low expression (2(-)(ΔΔ)(CT) ≤ 1, n = 56) groups. Results: The HCCs did not differ from matched liver tissues in terms of ARD1 mRNA levels. The high expression group had more often microvascular invasion than the low expression group (32 vs. 14%; p = 0.045). The two groups did not differ significantly in terms of other patient or tumor variables. The median follow-up period was 92.1 months. The 5-year recurrence-free and overall survival rates were 34 and 76% for the high expression group, respectively, which were similar to the rates of the low expression group (46 vs. 73%, p = 0.98 and p = 0.52, respectively). Conclusions: Intratumoral ARD1 mRNA overexpression was involved in the microvascular invasion process in patients with HCC, although it did not associate strongly with postresectional outcomes.
Digestive Diseases 01/2012; 30(6):603-8. · 2.37 Impact Factor
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ABSTRACT: The study was aimed to investigate the relationship between plasma transforming growth factor beta 1 (TGF-β(1)) expression and the characteristics of hepatocellular carcinoma (HCC).
Five hundred and seventy-one patients with HCC were subjected. Plasma TGF-β(1) levels were measured by enzyme-linked immunosorbent assay at diagnosis and compared in accordance with clinical and radiological characteristics.
Plasma TGF-β(1) levels were significantly higher in the diffuse infiltrative type (n = 159) than in the nodular type of HCC (n = 412; 3.94 ± 0.34 vs. 3.79 ± 0.29 log(10) pg/ml; p < 0.001). They were much higher in patients with portal vein thrombosis or extrahepatic metastasis than in those without (3.88 ± 0.34 vs. 3.81 ± 0.29 log(10) pg/ml, p = 0.008; 3.94 ± 0.35 vs. 3.82 ± 0.30 log(10) pg/ml, p = 0.013, respectively). Also, plasma TGF-β(1) levels showed a positive correlation with the size of HCC (r = 0.014, p < 0.001). Additionally, plasma TGF-β(1) levels were inversely related to the survival periods (p < 0.001).
TGF-β(1) was overexpressed in invasive types of HCC and it may be involved in the rapid progression of HCC.
Oncology 01/2012; 82(1):11-8. · 2.27 Impact Factor
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ABSTRACT: To identify differences in radiologic assessment methods and determine optimal imaging criteria for response evaluation in hepatocellular carcinoma (HCC) patients treated with chemoembolization.
Institutional review board approval was obtained, and patient informed consent was waived. The present study included 332 patients with intermediate stage HCC and Child-Pugh A cirrhosis who underwent serial chemoembolization. All measurable target lesions of 1 cm or larger in diameter were uni- and bidimensionally measured both at baseline and during follow-up. Intermodel agreement among the guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST) were examined. The most reliable model was selected on the basis of the correlation with survival prediction.
The κ values of comparisons among WHO, RECIST, and mRECIST guidelines were less than 0.20, whereas the κ value for the comparison of EASL and mRECIST guidelines was 0.94. In patients with a partial response (PR), stable disease (SD), or progressive disease (PD), compared with patients with a complete response (CR), hazard ratios (HRs) for survival were 2.99 (95% confidence interval [CI]: 2.14, 4.17), 3.49 (95% CI: 1.71, 7.10), and 15.63 (95% CI: 9.51, 25.69), respectively, for EASL criteria. In patients with a PR, SD, or PD, compared with patients with a CR, the HRs were 2.75 (95% CI: 1.96, 3.87), 6.32 (95% CI: 3.67, 10.90), and 16.06 (95% CI: 9.76, 26.43), respectively, for mRECIST guidelines (P<.001). The C index for the multivariate model was 0.76 (95% CI: 0.72, 0.79) for both EASL and mRECIST guidelines, thus exhibiting satisfactory capability to help predict survival. The Cox regression model revealed that both mRECIST and EASL guidelines were independent predictors of overall survival (P<.001 for both).
The enhancement models more accurately helped predict long-term survival in HCC patients treated with chemoembolization.
Radiology 12/2011; 262(2):708-18. · 5.73 Impact Factor
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Jong Gi Choi,
Young-Hwa Chung,
Jeong A Kim,
Young-Joo Jin,
Won Hyung Park,
Danbi Lee,
Ju Hyun Shim,
Yoon Seon Lee,
Dong Dae Seo,
Myoung Kuk Jang, Kang Mo Kim,
Young-Suk Lim,
Han Chu Lee,
Yung Sang Lee,
Eunsil Yu,
Young Joo Lee
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ABSTRACT: In this study the authors intended to investigate the relationship between intrahepatic hepatitis B virus (HBV)-DNA concentrations and posthepatectomy recurrence of HBV-associated hepatocellular carcinoma (HCC).
High HBV-DNA level is strongly associated with HCC development in chronic HBV infection and considered to be a risk factor of HCC recurrence.
A total of 109 patients with HBV-associated HCC who underwent curative surgical resection were followed up every 3 to 6 months for a median of 82 months. Intrahepatic total HBV-DNA titer was measured in HCC and surrounding liver tissues using a TaqMan probe-based real-time polymerase chain reaction method. HBV-DNA titers in HCC and surrounding liver were compared in accordance with patients' clinical, radiologic, and histopathological characteristics. The relationships between HBV-DNA titers in HCC or surrounding liver tissues and cumulative HCC recurrence rates were determined.
Of the 109 patients, 67 (62%) showed posthepatectomy recurrence of HCC. In all patients, total HBV-DNA titers were significantly higher in HCCs than in surrounding liver tissues (P=0.019). HCC recurred more frequently in patients with higher than those with lower HBV-DNA titers in surrounding liver tissues (P=0.009). In contrast, the HCC recurrence rates were similar in patients with higher and those with lower HBV-DNA titers in HCC specimens (P=0.301). Multivariate analysis showed that tumor size >5 cm (P=0.008), the presence of portal vein thrombus (P=0.001), and high HBV-DNA titer in surrounding liver tissues (P=0.002) were independent risk factors for posthepatectomy HCC recurrence in patients with HBV-associated HCC.
In patients with HBV-associated HCC, high HBV-DNA titer in surrounding liver rather than in the HCC itself is associated with posthepatectomy HCC recurrence after curative surgical resection.
Journal of clinical gastroenterology 11/2011; 46(5):413-9. · 2.21 Impact Factor
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ABSTRACT: We investigated the efficacy and effectiveness of entecavir in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients.
We enrolled 231 nucleoside-naïve chronic hepatitis B (CHB) patients primarily treated with entecavir 0.5 mg/day for at least 6 months in our institution. Of these, 71 patients had HCC at the start of entecavir treatment (HCC group) and 160 did not (non-HCC group). We compared antiviral responses to entecavir in the two groups, and evaluated the effects of entecavir on the clinical outcomes of curatively-treated HCC patients.
The HCC and non-HCC groups had similar cumulative rates of HBV-DNA negativity, alanine aminotransferase normalization, and hepatitis e antigen loss in year 2 (100% vs 95.4%, 94.7% vs 97.3%, and 40.8% vs 41.8%, respectively; P > 0.05). Entecavir treatment for 12 months decreased mean Model for End-Stage Liver Disease scores in patients with cirrhosis and HCC (7.2 vs 5.6, P < 0.001). Of the 71 HCC patients, 16 underwent curative therapies concurrently with entecavir; hepatectomy in six and radiofrequency ablation in 10, and the 55 remaining patients received transarterial chemoembolization or conservative treatment. In a subgroup of 16 HCC patients receiving curative treatments, patients who became serum HBV DNA negative by week 24 had better overall survival (P = 0.039), but not recurrence-free survival (P = 0.961), than those who did not.
First-line entecavir monotherapy is comparably effective in CHB patients with and without HCC, and improves hepatic function in HBV-related HCC patients. An early virological response to entecavir is prognostic of improved survival following curative therapy against HBV-related HCC.
Journal of Gastroenterology and Hepatology 09/2011; 26(9):1380-8. · 2.87 Impact Factor
