Kyu Won Chung

Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection. Stereotactic radiotherapy for liver cancer

BackgroundWe evaluated the long-term effect of stereotactic body radiation therapy (SBRT) for primary small hepatocellular carcinoma (HCC) ineligible for local therapy or surgery.MethodsForty-two HCC patients with tumors ≤ 100 cc and ineligible for local ablation therapy or surgical resection were treated with SBRT: 30-39 Gy with a prescription isodose range of 70-85% (median 80%) was delivered daily in three fractions. Median tumor volume was 15.4 cc (3.0-81.8) and median follow-up duration 28.7 months (8.4-49.1).ResultsComplete response (CR) for the in-field lesion was initially achieved in 59.6% and partial response (PR) in 26.2% of patients. Hepatic out-of-field progression occurred in 18 patients (42.9%) and distant metastasis developed in 12 (28.6%) patients. Overall in-field CR and overall CR were achieved in 59.6% and 33.3%, respectively. Overall 1-year and 3-year survival rates were 92.9% and 58.6%, respectively. In-field progression-free survival at 1 and 3 years was 72.0% and 67.5%, respectively. Patients with smaller tumor had better in-field progression-free survival and overall survival rates (<32 cc vs. ≥32 cc, P < 0.05). No major toxicity was encountered but one patient died with extrahepatic metastasis and radiation-induced hepatic failure.ConclusionsSBRT is a promising noninvasive-treatment for small HCC that is ineligible for local treatment or surgical resection.

Serum interleukin-6 and C-reactive protein as a prognostic indicator in hepatocellular carcinoma

The development of hepatocellular carcinoma (HCC) is often associated with chronic inflammation, suggesting a strong relationship between inflammation and carcinogenesis. This study evaluated the prognostic values of inflammatory and T-helper (Th) cytokines in the clinical outcome and survival of HCC. The study included 110 patients with HCC undergoing loco-regional therapy and 24 healthy controls. Five Th1/Th2 cytokines and C-reactive protein (CRP) were quantified before and after loco-regional treatment, using enzyme-linked immunosorbent assays. Levels of CRP, interleukin (IL)-4, and IL-6 were higher in patients with HCC than those in healthy subjects. Tumor characteristics, Child-Pugh class, and CRP, IL-6, and IL-10 levels were associated with HCC survival (all P<0.05). With multivariate analysis, higher IL-6 levels were identified as the independent cytokine for shorter survival (P=0.010). Higher CRP and IL-6 levels correlated well with larger tumor size, poor Child-Pugh function, and shorter survival, with a significant inter-correlation (r=0.667). On serial measurements, the association of CRP with tumor response was stronger than that of α-fetoprotein or other cytokines. IL-6 and CRP are strong inflammatory indicators predictive of outcome in patients with HCC receiving loco-regional therapy. This study suggests that inflammatory activation of the IL-6/CRP network may be a potential therapeutic target and biomarker for HCC.

The Human Cervical Cancer Oncogene Protein Is a Biomarker for Human Hepatocellular Carcinoma

Human cervical cancer oncogene (HCCR) was identified and appeared to function as a negative regulator of p53 gene. The objective of this study was to validate HCCR expression as a candidate marker for human hepatocellular carcinoma. HCCR epitope was identified as Y355LGTRR360. According to immunofluorescence study, HCCR was predominantly localized in the plasma membrane and cytoplasm of hepatocellular carcinoma. HCCR proteins were overexpressed in the tumorous compared with the nontumorous cirrhosis tissues. However, HCCR was not detected in normal liver tissue. Concentration of HCCR protein in the serum was measured in a total of 570 subjects, and comparisons were made to α-fetoprotein. Serological studies revealed 78.2% sensitivity of HCCR (cutoff value, 15 μg/ml), which was significantly higher than 64.6% of α-fetoprotein (P = 0.0098) and 95.7% specificity for hepatocellular carcinoma. Forty of 52 (76.9%) patients with carcinoma negative for α-fetoprotein showed positive values for HCCR. A positive rate of 69.2% in carcinoma patients with tumor sizes <2 cm was found to be a higher rate than measurement of α-fetoprotein. Furthermore, HCCR expression was also detected in liver cirrhosis at an intermediate level between carcinoma and normal groups, which gave 88.1% sensitivity and 79.0% specificity using 8 μg/ml as a cutoff value. In summary, the HCCR assay may have an advantage over the α-fetoprotein assay in that it is elevated according to disease progression from liver cirrhosis to carcinoma, and it is more frequently positive in patients with early, small hepatocellular carcinoma.

Spontaneous regression of a large hepatocellular carcinoma with skull metastasis

Abstract  Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. This case of a 65‐year‐old Korean man with HCC and metastatic frontal bone mass that regressed after radiotherapy for frontal bone mass without any other therapeutic modalities is described. The clinical diagnosis of HCC was made because of the presence of a liver mass on abdominal computed tomography (CT) scan, high serum α‐fetoprotein value and tissue diagnosis on frontal bone biopsy. The patient refused any other recommended treatments, but accepted the radiation therapy due to a painful frontal bone mass, and ingested mushroom called Phellinus linteus for one and a half years. Ten months after radiation therapy, he experienced a reduction in size of the frontal bone mass and improvement of lesions in the liver, sternum and ribs. The patient is alive and in good condition without any symptoms or tumor aggravation in August 2002. It was concluded that a rare case of spontaneous regression of HCC had occurred.

Long-Term Results of Lamivudine Monotherapy in Korean Patients with HBeAg-Positive Chronic Hepatitis B: Response and Relapse Rates, and Factors Related to Durability of HBeAg Seroconversion

Objective: The aim of this study was to evaluate retrospectively the long-term effects of lamivudine in 461 Korean patients with chronic hepatitis B who were treated for more than 12 months. Methods: The annual rates of virological response and breakthrough were examined and the predictive factors for post-treatment relapse in 114 patients who achieved hepatitis B e antigen (HBeAg) loss or seroconversion after lamivudine therapy were also analyzed. Results: During follow-up, the rates of HBeAg seroconversion after 1, 2, 3, 4 and 5 years of treatment were 22.9, 33.2, 47.6, 54.2 and 58.8%, respectively, while those for virological breakthrough at 1, 2, 3 and 4 years were 8.2, 41.7, 55.7 and 64.8%, respectively. Ninety-five patients (20.6%) had HBeAg seroconversion and 19 (4.1%) showed HBeAg loss alone with disappearance of hepatitis B virus DNA in serum. Seroconversion was higher with prolonged treatment in patients who had elevated serum alanine aminotransferase. The cumulative relapse rates in the seroconversion group were 52.0 and 55.7% 1 and 2 years after treatment, respectively. Age and the duration of additional treatment were significant predictive factors for post-treatment relapse. Patients aged ≤40 who had additional treatment for >12 months after seroconversion had the lowest relapse rate (p < 0.001). Conclusions: These results suggest that additional treatment for over 12 months after HBeAg seroconversion in younger patients may produce a better long-term outcome.

A case of acute cholestatic hepatitis associated with the seeds of Psoralea corylifolia (Boh-Gol-Zhee).

The potential hepatotoxicity of herbal remedies is usually ignored in daily life. One such compound, Boh-Gol-Zhee (in Chinese, Bu Ku Zi), appeared to be associated with the occurrence of acute cholestatic hepatic injury in the following case. Some alternative medicine therapists claim that Psoralea corylifolia is effective for the treatment of osteoporosis. We observed a case of acute cholestatic hepatitis associated with the use of the seeds of Psoralea corylifolia in amounts over 10 times the usual dose in a postmenopausal woman. Liver biopsy showed zone three necroses, degenerating cells, cholestasis, and infiltrations with inflammatory cells. This case stresses the need to warn of the potential hepatotoxicity of the seed of Psoralea corylifolia, especially in a large dose.

Risk of HBV reactivation according to viral status and treatment intensity in patients with hepatocellular carcinoma.

BACKGROUND There are no convincing data supporting the routine use of pre-emptive therapy against HBV reactivation in various loco-regional therapies for hepatocellular carcinoma (HCC). This study investigated the incidence, severity and risk factors of HBV reactivation during loco-regional therapies. METHODS A total of 205 prospectively enrolled patients were classified in order of increasing intensity of loco-regional therapies: local ablation therapy (LAT; 43 patients), transarterial chemotherapy using adriamycin (TAC-ADR; 93 patients) or combined epirubicin-cisplatin (TAC-EC; 26 patients), and combined chemo-radiotherapy (TAC-EC+RT; 43 patients). RESULTS During the follow-up, 62 (30.2%) patients developed HBV reactivation. Multivariate analysis identified HBV DNA levels >10⁴ copies/ml (P=0.041) and treatment option (P=0.001) to be independent predictors of HBV reactivation. There was a significant trend for increasing risk of reactivation with increasing intensity of therapy, with hazard ratios of 1.0 for LAT, 2.45 for TAC-ADR, 4.19 for TAC-EC and 10.17 for TAC-EC+RT. The severity of reactivated disease was also increased with increasing treatment intensity (P-value for trend <0.05). Only one of the patients with low-level viraemia receiving LAT alone developed reactivation, whereas a substantial number of patients with high-level viraemia eventually developed reactivation. CONCLUSIONS High-level viraemia and high-level treatment intensity are the major risk factors for HBV reactivation during loco-regional therapy. Trends are evident for the increased risk and severity of reactivation with the aggressiveness of treatment. Pre-emptive antiviral therapy should be recommended for all patients with high-level viraemia irrespective of treatment option, or those undergoing any intensive therapy.

Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation -- a pilot study.

Abstract: Purpose: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute‐on‐chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT).

Association between human leukocytes antigen alleles and chronic hepatitis C virus infection in the Korean population.

Abstract: Background/Aim: Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population.

Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases.

Background and Aim:  There has been little information about the long‐term outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. The purpose of this study was to investigate the clinical factors affecting survival after extrahepatic metastasis and to determine the survival benefit of controlling intrahepatic HCC.