Hyung-Don Kim

Quantitative polymerase chain reaction assay for serum hepatitis B virus DNA as a predictive factor for post-treatment relapse after lamivudine induced hepatitis B e antigen loss or seroconversion

Background and aims: Lamivudine induces favourable virological and biochemical responses but post-treatment relapses are frequent, even in patients with hepatitis B e antigen (HBeAg) loss or seroconversion. The aim of this study was to determine whether extended lamivudine therapy for up to 12 months after HBeAg loss/seroconversion could decrease the risk of post-treatment virological relapse. In addition, we monitored serum hepatitis B virus (HBV) DNA levels using a quantitative polymerase chain reaction (PCR) assay during extended lamivudine therapy and analysed predictive factors for post-treatment relapse. Patients and methods: A total of 49 patients who exhibited HBeAg loss/seroconversion during lamivudine therapy received extended lamivudine therapy for six months (group 1, n = 23) or 12 months (group 2, n = 26) after HBeAg loss/seroconversion. Serum HBV DNA levels were quantified by a PCR based assay at the time of HBeAg loss/seroconversion, and at cessation of therapy. Results: Post-treatment virological relapse rates at two years were 59% in group 1 and 50% in group 2. Age, time interval to HBeAg loss/seroconversion, and serum HBV DNA levels at the time of cessation of therapy were independent predictive factors for post-treatment relapse. The post-treatment relapse rate was 37% at two years in patients with serum HBV DNA levels of <200 copies/ml but 73% in those with ⩾103 copies/ml. Conclusions: Extended lamivudine therapy for up to 12 months did not decrease the rate of post-treatment virological relapse, and monitoring of serum HBV DNA by a quantitative PCR method was helpful in predicting post-treatment relapse.

Evaluation of Early-Stage Hepatocellular Carcinoma by Magnetic Resonance Imaging With Gadoxetic Acid Detects Additional Lesions and Increases Overall Survival

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) has a high rate of intrahepatic recurrence after curative treatment, possibly because metastases are not always identified before treatment. Magnetic resonance (MR) imaging with a liver-specific contrast agent, gadoxetic acid, can detect small HCCs with high levels of sensitivity. We investigated whether MR imaging with gadoxetic acid increases overall and recurrence-free survival of patients initially assessed by computed tomography (CT). METHODS We performed a retrospective study of data from 700 patients diagnosed with a single-nodular HCC by dynamic 4-phase CT in Seoul, Korea, from January 2009 through December 2010. Of these patients, 323 underwent additional evaluation with gadoxetic acid-enhanced MR imaging (CT+MR group). The 377 patients who did not undergo MR imaging analysis are referred to as the CT group. RESULTS The CT and CT+MR groups were comparable in most baseline characteristics (Child-Pugh class A, 93.1% vs 94.7%; and median size of the primary HCCs, 2.8 vs 2.6 cm, respectively). Seventy-four additional HCC nodules were detected in 53 (16.4%) of the patients who underwent MR evaluation after CT (CT+MR group). These detections increased the Barcelona Clinic Liver Cancer stages for 43 patients (13.3%) and modified their treatment plans. On multivariable analyses, the CT+MR group had a significantly lower rate of HCC recurrence (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.54-0.96) and lower overall mortality (HR, 0.65; 95% CI, 0.44-0.96) than the CT group. In an analysis of 285 pairs of patients matched on the basis of the propensity score, the CT+MR group had significantly lower overall mortality (HR, 0.66; 95% CI, 0.44-0.99). CONCLUSIONS Among patients who underwent dynamic CT analysis of a single-nodular HCC, additional evaluation by MR imaging with gadoxetic acid led to the detection of additional HCC nodules in 16% of patients, reduced the risk of disease recurrence, and decreased overall mortality.

Optimal methods for measuring eligibility for liver transplant in hepatocellular carcinoma patients undergoing transarterial chemoembolization

BACKGROUND & AIMS We investigated the optimal radiologic method for measuring hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) in order to assess suitability for liver transplantation (LT). METHODS 271 HCC patients undergoing TACE prior to LT were classified according to both Milan and up-to-seven criteria after TACE by using the enhancement or size method on computed tomography images. The cumulative incidence function curves with competing risks regression was used in post-LT time-to-recurrence analysis. The predictive accuracy for recurrence was compared using area under the time-dependent receiver operating characteristic curves (AUC) estimation. RESULTS Of the 271 patients, 246 (90.8%) and 164 (60.5%) fell within Milan and 252 (93.0%) and 210 (77.5%) fell within up-to-seven criteria, when assessed by enhancement and size methods, respectively. Competing risks regression analyses adjusting for covariates indicated that meeting the criteria by enhancement and by size methods was independently related to post-LT time-to-recurrence in the Milan or up-to-seven model. Higher AUC values were observed with the size method only in the up-to-seven model (p<0.05). Mean differences in the sum of tumor diameter and number of tumors between pathologic and radiologic findings were significantly less by the enhancement method (p<0.05). Cumulative incidence curves showed similar recurrence results between patients with and without prior TACE within the criteria based on either method, except for the within up-to-seven by the enhancement method (p=0.017). CONCLUSIONS The enhancement method is a reliable tool for assessing the control or downstaging of HCC within Milan after TACE, although the size method may be preferable when applying the up-to-seven criterion.

Isolated perihepatic tuberculosis: imaging findings

AIM To review the imaging findings of isolated perihepatic tuberculosis without coexistent active tuberculosis elsewhere in the body. MATERIALS AND METHODS Over a 9-year period, six patients with histopathologically proven perihepatic tuberculosis without simultaneous active tuberculosis elsewhere in the body were included in this study. Two radiologists retrospectively evaluated in consensus the location (right, left, or both perihepatic spaces), size (maximum diameter), morphology (ovoid or round), number, attenuation (low-, iso-, or high-attenuation compared with the adjacent liver parenchyma), and the presence or absence of contrast enhancement of the lesions on computed tomography (CT), and echogenicity (low-, iso-, or high-echogenicity compared with the adjacent liver parenchyma) of the lesions on ultrasonography. RESULTS On CT, an isolated perihepatic lesion was located in the right perihepatic space in five patients, whereas three lesions were located in both perihepatic spaces in the remaining patient. The mean maximum diameter of the isolated perihepatic tuberculosis lesions was 29.7 mm. Isolated perihepatic tuberculosis appeared as an ovoid-shaped, homogeneous, and low-attenuating (n=5) or high-attenuating (n=1) lesion relative to the liver. There was peripheral rim enhancement of the lesion in two patients. On ultrasonography, isolated perihepatic tuberculosis was revealed as a homogeneous, low-echoic (n=5) or iso-echoic (n=1) lesion relative to the liver. CONCLUSION Although various inflammatory or malignant lesions can be located in the perihepatic space, isolated perihepatic tuberculosis appears an ovoid-shaped, homogeneous, and low-attenuating or low-echoic lesion compared with the liver parenchyma on CT or ultrasonography.

Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis B vs Chronic Hepatitis C after Achievement of Virologic Response

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg‐interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow‐up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30‐3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg‐interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.

Correction to: Tumor Volume Doubling Time as a Dynamic Prognostic Marker for Patients with Hepatocellular Carcinoma

The original version of this article unfortunately contained an error in corresponding author e-mail. It was submitted and published as kimkim70@amc.seoul.kr instead of kimkm70@amc.seoul.kr.

Impact of the Interval between Transarterial Chemoembolization Sessions on Survival in Patients with Unresectable Hepatocellular Carcinoma

PURPOSE To evaluate clinical impact of different intervals between multiple transarterial chemoembolization sessions in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS A retrospective cohort study of 305 consecutive patients with HCC who underwent multiple sessions of on-demand transarterial chemoembolization by two independent physicians with different management policies in terms of transarterial chemoembolization interval was performed; 180 patients had intervals between the first and second transarterial chemoembolization session of < 60 days (short-interval group), and 125 patients had transarterial chemoembolization intervals of ≥ 60 days (conventional-interval group). RESULTS The short-interval group had more cases of advanced-stage HCC, less favorable response to transarterial chemoembolization, and higher likelihood of having Child-Pugh class A. The short-interval group underwent more transarterial chemoembolization sessions (6.6 vs 5.5, P = .011), although the total number of admissions and total hospital stay were similar to the conventional-interval group. Overall survival was similar in the two groups in the full and the propensity score-matched cohorts. Although the overall survival of patients with Child-Pugh class A was comparable between the two groups in the full and propensity score-matched cohorts, the short-interval group showed inferior survival (P = .005) and a nonsignificant trend toward inferior survival (P = .117) in the full and propensity score-matched cohorts, respectively, for patients with Child-Pugh class B. CONCLUSIONS Transarterial chemoembolization interval did not affect survival outcomes of patients with Child-Pugh class A. A shorter transarterial chemoembolization interval showed a nonsignificant trend of adversely affecting survival for patients with Child-Pugh class B.

[296] DOWN-REGULATION OF SURVIVIN IN GROWTH INHIBITION OF HEPATOMA CELLS INDUCED BY SELECTIVE CYCLOOXYGENASE-2 INHIBITOR

Background/Aims: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. Methods: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 µM), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. Results: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. Conclusions: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC. (Korean J Hepatol 2008;14:351-359)