Moon Seok Choi

Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: Analysis of prognostic factors

BACKGROUND & AIMS The aim was to assess 10-year outcomes of radiofrequency ablation as a first-line therapy of early-stage hepatocellular carcinoma with an analysis of prognostic factors. METHODS From April 1999 to April 2011, 1305 patients (male:female=993:312; mean age, 58.4 years) with 1502 early-stage hepatocellular carcinomas (mean size, 2.2 cm) were treated with percutaneous radiofrequency ablation as a first-line option. Follow-up period ranged from 0.4 to 146.6 months (median, 33.4 months). We assessed the 10-year follow-up results of recurrences and survival with the analyses of prognostic factors. RESULTS Recurrences occurred in 795 patients (1-17 times), which were managed with various therapeutic modalities. The cumulative local tumor progression rates were 27.0% and 36.9% at 5 and 10 years, respectively, for which the only significant risk factor was large tumor size (B=0.584, p=0.001). Cumulative intrahepatic distant and extrahepatic recurrence rates were 73.1% and 88.5%, and 19.1% and 38.2% at 5 and 10 years, respectively. Corresponding overall survival rates were 59.7% and 32.3%, respectively. Poor survival was associated with old age (B=0.043, p=0.010), Child-Pugh class B (B=-1.054, p<0.001), absence of antiviral therapy during follow-up (B=-0.699, p=0.034), and presence of extrahepatic recurrence (B=0.971, p=0.007). CONCLUSIONS Ten-year survival outcomes after percutaneous radiofrequency ablation as a first-line therapy of hepatocellular carcinoma were excellent despite frequent tumor recurrences. Overall survival was influenced by age, Child-Pugh class, antiviral therapy, or extrahepatic recurrence.

Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease

Background It is generally stated that oral antiviral therapy in patients with chronic hepatitis B (CHB) decreases the risk of developing hepatocellular carcinoma (HCC). Although oral nucleos(t)ide analogues (NUCs) may induce a state similar to inactive stage CHB, the long-term risk for HCC in patients treated with NUCs compared with inactive CHB is unclear. Methods A total of 1378 patients who were treatment naïve and started NUC therapy and 1014 patients with inactive stage CHB who were HBeAg-negative and continuously had hepatitis B DNA <2000 IU/mL during follow-up were enrolled. The NUC group was divided into two groups by continuous viral suppression: NUC complete responder (CR) group and NUC incomplete responder (IR) group. Cumulative HCC incidence rates were compared between the groups. Results The risk of developing HCC was significantly higher in the NUC CR group compared with the inactive CHB group, regardless of the presence of baseline liver cirrhosis (p<0.001). Risk factors associated with the development of HCC were treatment groups (p<0.001), age (p<0.001), sex (p<0.001) and the presence of liver cirrhosis at baseline (p=0.005). Of the NUC group, the cumulative incidence of HCC in the NUC IR group was significantly higher compared with the NUC CR group (p=0.028). Conclusions The use of potent oral antiviral therapy can effectively suppress HBV replication in patients with CHB. However, the risk of HCC development in patients treated with oral antiviral agent is still significantly higher than patients with inactive stage CHB.

2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma

The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.

Inactive Hepatitis B Surface Antigen Carrier State and Hepatotoxicity During Antituberculosis Chemotherapy

STUDY OBJECTIVES To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide. DESIGN Retrospective case-control study. SETTING Tertiary university medical center. PATIENTS One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects. RESULTS The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects). CONCLUSIONS Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.

Ultrasonographically Detected Non-Alcoholic Fatty Liver Disease Is an Independent Predictor for Identifying Patients With Insulin Resistance in Non-Obese, Non-Diabetic Middle-Aged Asian Adults

OBJECTIVES:We assessed the association among ultrasonographically detected non-alcoholic fatty liver disease (US-NAFLD), metabolic syndrome (MetS), and insulin resistance (IR) in non-obese, non-diabetic middle-aged adults, to find out whether US-NAFLD is independently associated with IR in this population.METHODS:A total of 5,878 non-obese (body mass index, ≥18.5 and <25), non-diabetic individuals were analyzed. IR was estimated with the homeostasis model assessment index (HOMA2–IR) and defined when HOMA2–IR ≥1.5. MetS was defined by the Adult Treatment Panel III (ATP III) criteria.RESULTS:MetS was present in 381 (6.5%) participants, IR was present in 801 (13.6%) participants, and US-NAFLD was present in 1,611 (27.4%) participants. The increase in the prevalence of US-NAFLD closely followed the increase in the number of metabolic components diagnosed according to the ATP III criteria (15.2%, 28.5%, 48.0%, 65.7%, 71.4%, and 100% for 0, 1, 2, 3, 4, and 5 metabolic components, respectively, P<0.001). US-NAFLD showed a significantly higher odds ratio (OR) for IR, regardless of the number of metabolic components (OR (95% confidence interval) of 3.48 (2.45–4.94), 3.63 (2.74–4.82), 3.19 (2.29–4.44), and 2.43 (1.43–3.81) for 0, 1, 2, and ≥3 metabolic components, respectively, P<0.001 for all values). MetS showed a low sensitivity (0.22) for the identification of individuals with IR, and either US-NAFLD alone (0.60) or US-NAFLD with MetS (0.66) improved sensitivity with acceptable trade-off in specificity.CONCLUSIONS:US-NAFLD was an independent predictor for IR, irrespective of the number of metabolic components of MetS in the non-obese, non-diabetic middle-aged Asian adults. US-NAFLD could identify individuals with IR that cannot be identified by MetS in this population.

Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in Asian patients.

Background and Aims:  A single nucleotide polymorphism near the interleukin‐28B (IL28B) gene has been shown to predict hepatitis C virus (HCV) treatment response. We aim to determine the role of the IL28B genotype in Asian patients.

Disease progression and the risk factor analysis for chronic hepatitis C

Background/Aims: The present study aimed to assess the incidence of advanced cirrhotic complications and to identify the risk factors associated with such complications in chronic hepatitis C.

Effect of balloon-occluded retrograde transvenous obliteration on the natural history of coexisting esophageal varices.

Background and Aims Balloon-occluded retrograde transvenous obliteration (BRTO) provides an effective mean of controlling gastric variceal (GV) bleeding; however, increased portal pressure after the obliteration of gastrorenal shunts may lead to a worsening and subsequent rupture of esophageal varices (EV). The aim of this study was to determine whether the natural history of coexisting EV is affected by BRTO. Methods Two hundred thirty-seven patients with gastric varices and no history of EV or GV bleeding at the time of diagnosis were included. Clinical, laboratory, and endoscopic features were compared between 25 patients who underwent BRTO due to GV bleeding (BRTO group) and 198 patients who never experience GV bleeding (control group) during follow-up. The incidences of EV bleeding were evaluated and compared between these 2 groups. Results The BRTO and control groups were not significantly different with respect to baseline characteristics including age, sex, etiologies of cirrhosis, hepatic function, and the classification or extent of EV and GV. During follow-up (median 48 mo), the overall incidence of first EV bleeding in the patients with fundal varices was significantly higher in the BRTO group (P=0.04). The incidences of EV bleeding were not different at 1 or 3 years (10.1% vs. 12.9%, P=0.32 and 39.3% vs. 38.4%, P=0.57), but became significantly higher in the BRTO group at 5 (72.2% vs. 48.5%, P=0.02) and 7 years (90.7% vs. 50.6%, P<0.01). Conclusions BRTO increased the bleeding rate of coexisting EV in the long term. Close monitoring and prophylaxis of EV bleeding may be warranted after BRTO.

Hepatocellular carcinoma risk in chronic hepatitis B virus–infected compensated cirrhosis patients with low viral load

Controversy exists about whether antiviral therapy (AVT) should be recommended for compensated cirrhosis patients with chronic hepatitis B virus (HBV) infection and detectable, but low, serum HBV‐DNA levels. A retrospective cohort of 385 treatment‐naïve, HBV‐related compensated cirrhosis patients (mean age: 51.1 ± 9.7 years; 66% male) with low HBV‐DNA levels (<2,000 IU/mL) was assessed for the development of hepatocellular carcinoma (HCC). During a median of 5.6 years of follow‐up, HCC had developed in 37 (9.6%) patients. The 5‐year cumulative HCC incidence rate was 2.2%, 8.0%, and 14.0% for patients with undetectable HBV DNA (<12 IU/mL), low HBV‐DNA levels plus normal alanine aminotransferase (ALT) levels, and low HBV‐DNA levels plus elevated ALT levels at baseline (P = 0.011). During follow‐up, 71 patients maintained undetectable HBV‐DNA levels, and 126 experienced HBV‐DNA elevation over 2,000 IU/mL. AVT was initiated in 77 patients. In patients without AVT, the 5‐year cumulative HCC incidence rates were 13.3%, 8.8%, and 1.4% for those who experienced HBV‐DNA elevation, those who maintained detectable, but low, HBV‐DNA levels, and those who maintained undetectable HBV‐DNA levels, respectively. The 5‐year cumulative HCC incidence rate was 5.9% for patients who started AVT; longer AVT duration and longer complete virological response (<12 IU/mL) duration was associated with lower HCC risk. Conclusion: Compensated cirrhosis patients with detectable, but low, viral load were not at low risk for HCC, and AVT was associated with lower HCC risk, suggesting that prompt AVT should be considered for these patients. (Hepatology 2015;62:694–701)

Early three-dimensional conformal radiotherapy for patients with unresectable hepatocellular carcinoma after incomplete transcatheter arterial chemoembolization: a prospective evaluation of efficacy and toxicity.

Purpose:We prospectively evaluated the efficacy and toxicity of early 3-dimensional conformal radiotherapy (3D-CRT) for patients with unresectable hepatocellular carcinoma (HCC) after incomplete transcatheter arterial chemoembolization (TACE). Methods:Patients with unresectable HCC who failed 1 or 2 courses of TACE were eligible for this study. Three dimensional-CRT was added for HCC with incomplete uptake of iodized oil. Between January 2006 and February 2007, 40 patients (43 lesions) were enrolled. TACE was performed by using Lipiodol and adriamycin, followed by Gelfoam embolization. Two cycles of TACE were performed in 24 patients (60%), whereas 16 patients (40%) underwent one cycle. The median dose of 54 Gy (3 Gy daily) was delivered with 3D-CRT. Tumor response was evaluated by changes in tumor size on serial computed tomography scans and toxicity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. Results:An objective response was achieved in 27 of 43 lesions (62.8%), with a complete response in 9 lesions (20.9%) and partial response in 18 lesions (41.9%). The overall survival rate was 72.0% at 1 year and 45.6% at 2 years. There was no grade 3 or greater acute toxicity. Nine patients (22.5%) showed progression of the disease within the irradiated field during the follow-up and intrahepatic metastases developed in 16 patients (40.0%). Conclusion:Early 3D-CRT for HCC unresponsive to 1 or 2 cycles of TACE resulted in a 62.8% tumor response rate and relatively high complete response rates (20.9%) with acceptable toxicity. This study shows that the application of 3D-CRT could be considered for patients with incomplete TACE.