-
[show abstract]
[hide abstract]
ABSTRACT: Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12.
In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months.
Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17-0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83-0.95; P = 0.044).
Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.
Liver international: official journal of the International Association for the Study of the Liver 03/2012; 32(7):1179-85. · 3.82 Impact Factor
-
Young Eun Chon,
Gi Hong Choi, Myoung Ha Lee,
Seung Up Kim,
Do Young Kim,
Sang Hoon Ahn,
Kyung Sik Kim,
Jin Sub Choi,
Kwang-Hyub Han,
Chae Yoon Chon,
Jun Yong Park
[show abstract]
[hide abstract]
ABSTRACT: Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are widely used complementary tumor markers for hepatocellular carcinoma (HCC). In this study, we investigated whether preoperative AFP and DCP levels predict recurrence after curative resection in patients with hepatitis B virus (HBV)-related HCC. Records for 267 patients who were diagnosed with HBV-related HCC and who underwent curative resection for HCC were retrospectively reviewed. Patients were divided into two preoperative groups: pre-op I (AFP ≥20 ng/dL and DCP ≥40 mAU/mL) and pre-op II (AFP ≥20 ng/dL and DCP <40 mAU/mL; AFP <20 ng/dL and DCP ≥40 mAU/mL; or AFP <20 ng/dL and DCP <40 mAU/mL). Among 267 patients, 102 (38.2%) patients were classified as pre-op I, whereas the other 165 (61.8%) belonged to pre-op II. During the post-resection follow-up [69.0 (3.0-136.0) months] period, 154 (57.7%) patients developed recurrences [68 (66.7%) patients in pre-op I vs. 86 (52.1%) in pre-op II, p = 0.029]. A multivariate analysis revealed that multiple tumors [hazard ratio (HR), 2.210; 95% confidence interval (CI), 1.185-4.121] and pre-op I (HR: 1.890; 95% CI; 1.080-3.289) were significant predictors for recurrence. Disease-free survival (DFS) was significantly shorter in pre-op I compared to that in pre-op II (20.0 vs. 46.8 months, p = 0.006). Elevated preoperative AFP and DCP levels were associated with a higher recurrence rate and shorter DFS in patients with HBV-related HCC after curative resection. The combined measurement of preoperative AFP and DCP may be a prognostic factor for future recurrence.
International Journal of Cancer 02/2012; 131(10):2332-41. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Few studies have reported on the clinical characteristics of hepatocellular carcinoma (HCC) at the time of diagnosis with regard to pre-S and basal core promoter (BCP) mutations. In this study, the clinical features and prognosis of 126 Korean HCC patients were examined with respect to pre-S deletion and BCP mutations of hepatitis B virus. The proportion of HCC patients according to tumor-node-metastasis stage are as follows: 8.7% in stage I, 31% in stage II, 30.2% in stage III, 21.4% in stage IV-A, and 8.7% in stage IV-B. Overall, 40.5% of HCC patients were treated by surgery or ablation, 59.5% by other methods. Patients were divided according to pre-S deletion and BCP mutations (103 without pre-S deletion, 23 with pre-S deletion; 44 without BCP mutation, 82 with BCP mutation). The tumor characteristics and prognosis were evaluated between the groups, including size, number, type, vessel invasion, portal vein thrombosis, and metastasis. No significant difference in tumor characteristics between the HCC patients with pre-S deletion was observed, compared with the HCC patients without pre-S deletion. In contrast, the survival rate was lower in those with pre-S deletion than in those without it (P = 0.024). No difference in tumor characteristics was found in non-BCP and BCP mutation patients. Unlike the pre-S deletion group, no difference was observed in survival rate between the non-BCP and BCP patients. In conclusion, pre-S deletion and BCP mutations did not affect the initial tumor features. However, pre-S deletion was an independent risk factor affecting HCC survival.
Journal of Medical Virology 12/2011; 83(12):2088-95. · 2.82 Impact Factor
-
Myoung Ha Lee,
Do Young Kim,
Ja Kyung Kim,
Hye Young Chang,
Se Hun Kang,
Han Jak Ryu,
Hye-Lim Ju,
Seung Up Kim,
Jung Min Lee,
Jun Yong Park,
Kwang-Hyub Han,
Chae Yoon Chon,
Sang Hoon Ahn
[show abstract]
[hide abstract]
ABSTRACT: The interactions among hepatitis B virus (HBV) mutations in developing hepatocellular carcinoma (HCC) remain unclear and thus we investigated the risk of HCC related with single or multiple HBV mutations in Korean patients infected with HBV subgenotype C2.
From January 2003 to December 2008, HBV isolates from 135 patients with HCC were compared with those from 135 patients without HCC, matching for age, gender, and HBeAg status. The prevalence of preS deletions and G1896A and A1762T/G1764A mutations was evaluated.
The frequency of preS deletions significantly differed between the non-HCC and HCC groups, with 6 (4.4%) versus 25 (18.5%) patients, respectively (p < 0.001). Additionally, the frequency of A1762T/G1764A mutations was higher in the HCC than the non-HCC group [82 (60.7%) versus 30 (22.2%), p < 0.001]. For combined mutations, the odds ratio (OR) was highest in patients with both preS deletions and the A1762T/G1764A mutation, with 1 (0.7%) versus 11 (8.1%) patients (p = 0.005; OR 11.887).
HCC was associated with preS deletions and A1762T/G1764A mutations, and the combination of both mutations had a stronger association with HCC in Korean patients infected with HBV subgenotype C2.
Intervirology 08/2011; 55(4):296-302. · 2.34 Impact Factor
-
Myoung Ha Lee,
Seung Up Kim,
Do Young Kim,
Sang Hoon Ahn,
Eun Hee Choi,
Kwang Hun Lee,
Do Yun Lee,
Jinsil Seong,
Kwang-Hyub Han,
Chae Yoon Chon,
Jun Yong Park
[show abstract]
[hide abstract]
ABSTRACT: The clinical utility of alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) as a predictor of treatment outcome in patients with advanced hepatocellular carcinoma (HCC) receiving hepatic artery infusional chemotherapy (HAIC) or concurrent chemoradiation therapy (CCRT) has been poorly defined.
Between January 2003 and December 2007, we enrolled 127 treatment-naïve patients who received HAIC (n = 60) or CCRT (n = 67) as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 20% from the baseline level.
AFP responders showed significantly better overall survival (OS) than non-responders among patients with HAIC (median 17.3 vs 6.4 months, P < 0.001) and with CCRT (median 17.6 vs 8.7 months, P = 0.014). DCP responders in the CCRT group also showed significantly better progression-free survival (PFS) than non-responders (median 9.2 vs 3.1 months, P < 0.001). Multivariate Cox regression analyses showed that AFP response was independently predictive of OS in both groups (P = 0.009 in HAIC and P = 0.008 in CCRT) whereas DCP only predicted PFS in patients with CCRT (P = 0.015).
Early on-treatment AFP response was predictive of OS in treatment-naïve patients with advanced HCC receiving HAIC and CCRT as an initial treatment modality. Furthermore, DCP response was useful for predicting PFS in patients with CCRT.
Journal of Gastroenterology and Hepatology 07/2011; 27(2):313-22. · 2.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: No study has reported on the comparative effect of adefovir (ADV) add-on lamivudine (LAM) versus switching to entecavir (ETV) in LAM-resistant patients with chronic hepatitis B. From October 2007 to September 2008, 92 consecutive LAM-resistant patients were enrolled (47 LAM+ADV and 45 ETV 1 mg). All patients were followed for at least 12 months. The parameters assessed included normalization of ALT, HBeAg seroconversion, undetectable HBV DNA, reduction of HBV DNA, and predictors of virologic response. In the LAM+ADV and ETV groups, the baseline DNA levels were 7.61 (5.19-9.49) and 7.10 (5.43-9.74)log(10)copies/ml, respectively. At month 12, a virologic response occurred in 18/47 (38.3%) and 11/45 (24.4%; P=0.182) patients; ALT normalization, in 39/41 (95.1%) and 36/40 (90.0%; P=0.432); HBeAg seroconversion, in 5.1% and 2.4% (P=0.606); and virologic breakthrough, in 2.1% and 11.1% (P=0.107), respectively. The mean reduction from the baseline HBV DNA level was greater in the LAM+ADV group at month 12 (3.80 ± 1.12 vs. 2.7 ± 1.32 log(10)copies/ml; P<0.001). In the multivariate analysis, the independent parameters related to a virologic response at month 12 were baseline ALT (OR=1.003, 95% CI=1.000-1.006, P=0.026) and baseline HBV DNA (OR=0.495, 95% CI=0.298-0.823, P=0.007). Compared with switching to ETV monotherapy, ADV add-on LAM therapy was more effective at reducing the viral load in patients with LAM resistance, and the baseline HBV DNA and ALT levels were independent predictors of the virologic response. However, ADV add-on therapy had limitations in patients with a higher baseline HBV DNA in LAM rescue therapy.
Journal of Medical Virology 11/2010; 82(11):1835-42. · 2.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This report describes a patient with hepatic congestion due to right heart failure mimicking liver tumor. The patient had a history of breast cancer and left total mastectomy 30 years ago, tricuspid valve regurgitation and tricuspid valve replacement 4 years ago. Three years ago, abdominal contrast-enhanced computed tomography (CT) was performed to evaluate inguinal hernia, which revealed multiple small hepatic nodules. After 1 year, the number and size of liver nodules were increased in CT scan. The patient underwent gun biopsy and histopathology revealed sinusoid enlargement. The patient recently had jaundice, abdominal distension, and peripheral edema. Liver dynamic CT scan was done to evaluate the palpable liver. The number and size of liver nodules were more increased in CT than 2 years ago. In magnetic resonance imaging (MRI), numerous variable sized ill-defined nodules replacing entire liver with progressing centripetal enhancement, which were suggestive of malignancy such as angiosarcoma, were noted. MRI finding suspects malignancy or hemangiosarcoma. Finally, the patient received repeated gun biopsy, and histopathology revealed findings compatible with hepatic congestion.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 10/2010; 56(4):264-7.
