Jung Woo Shin

Transforming growth factor‐β1 as a useful serologic marker of small hepatocellular carcinoma

Although alpha‐fetoprotein (AFP) is a useful serologic marker of hepatocellular carcinoma (HCC), it has been reported insufficiently sensitive in detecting small HCCs. Plasma transforming growth factor‐β1 (TGFβ1) has been reported to be elevated in HCC patients compared with liver cirrhosis patients. It has been reported that TGFβ1 mRNA was overexpressed in HCC, especially in patients with small HCC and well‐differentiated HCC compared with patients with liver cirrhosis. The current study investigated the usefulness of TGFβ1 compared with AFP in the diagnosis of small HCCs.

Long-term additional lamivudine therapy enhances durability of lamivudine-induced HBeAg loss: a prospective study

BACKGROUNDS/AIMS In the treatment of chronic hepatitis B (CHB) with lamivudine, adequate duration of the therapy remains to be determined. In this prospective study, the authors intended to investigate whether long-term additional administration of lamivudine might enhance the durability of lamivudine-induced HBeAg seroconversion. METHODS Eighty-five CHB patients who achieved HBeAg seroconversion by lamivudine received additional lamivudine therapy for at least 24 months at a dose of 100 mg per day. Among them, 61 patients whose serum HBeAg and HBV-DNA (solution hybridization assay) had been negative persistently for >24 months discontinued lamivudine therapy and followed-up for >12 months. We calculated the cumulative reappearance rate of serum HBV-DNA and HBeAg and also evaluated the predictive factors for post-treatment virologic relapse. RESULTS The cumulative reappearance rates of serum HBV-DNA following cessation of lamivudine therapy at 6 months, 1 year and 2 years were 15%, 21%, and 31%, respectively. The cumulative reappearance rates of serum HBeAg at 6 months, 1 year and 2 years were 11%, 13% and 16%, respectively. Old age and presence of precore mutant were two independent predictive factors for viral relapse. CONCLUSION These results suggested that long-term additional administration of lamivudine might enhance the durability of lamivudine-induced HBeAg seroconversion.

Molecular Epidemiology of Hepatitis B Virus (HBV) Genotypes and Serotypes in Patients with Chronic HBV Infection in Korea

Objectives: Although hepatitis B virus (HBV) is endemic to Korea, no large-scale survey of HBV genotypes and serotypes based on sequence analysis has been performed. Methods: In the present study, we genotyped and serotyped HBV strains from 209 patients in two Korean regions, Seoul (107 patients) and Jeju (102 patients), an island off the southeastern Korean coast. Analyses were conducted using the direct sequencing method targeting the partial surface (S) gene (541 bp). Results: Phylogenetic analysis showed that all HBV strains from the 209 patients belonged to genotype C2 (100%). Of the 209 patients, 193 (92.3%), 12 (5.7%) and 1 (0.5%) were found to have the adr, adw and ayr serotypes, respectively. The other three strains (1.5%) showed unique serotype and were not typeable by sequence analysis. No HBV strains characteristic of Jeju island were observed. Conclusions: The extraordinary predominance of genotype C2 in chronic Korean patients, which is known to be associated with more severe liver disease than genotype B, suggests that the clinical manifestations of Korean HBV chronic patients are likely to differ from those found in other Asian countries, especially in Japan and Taiwan, where genotypes B and C coexist.

Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization1

Background and Aims: The aim of this study was: (i) to define the characteristics of hepatocellular carcinoma (HCC) associated with recurrences following initial remission by transcatheter arterial chemoembolization (TACE); (ii) to evaluate the patterns of recurrences; and (iii) find a better surveillance method of detecting recurrent HCC.

Recent increase in antibiotic‐resistant microorganisms in patients with spontaneous bacterial peritonitis adversely affects the clinical outcome in Korea

Background and Aim:  Recently, antibiotic‐resistant microorganisms have been increasingly noted in Korean patients with spontaneous bacterial peritonitis (SBP). The present study investigated the changing pattern of antibiotic resistance and its effects on the clinical outcome in treating SBP.

Molecular targeted therapy for hepatocellular carcinoma: current and future.

Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide. The majority of HCC cases occur in patients with chronic liver disease. Despite regular surveillance to detect small HCC in these patients, HCC is often diagnosed at an advanced stage. Because HCC is highly resistant to conventional systemic therapies, the prognosis for advanced HCC patients remains poor. The introduction of sorafenib as the standard systemic therapy has unveiled a new direction for future research regarding HCC treatment. However, given the limited efficacy of the drug, a need exists to look beyond sorafenib. Many molecular targeted agents that inhibit different pathways involved in hepatocarcinogenesis are under various phases of clinical development, and novel targets are being assessed in HCC. This review aims to summarize the efforts to target molecular components of the signaling pathways that are responsible for the development and progression of HCC and to discuss perspectives on the future direction of research.

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.

Whole Blood and Red Blood Cell Manganese Reflected Signal Intensities of T1-Weighted Magnetic Resonance Images better than Plasma Manganese in Liver Cirrhotics

Whole Blood and Red Blood Cell Manganese Reflected Signal Intensities of T1‐Weighted Magnetic Resonance Images better than Plasma Manganese in Liver Cirrhotics: Younghee Choi, et al. Department of Occupational and Environmental Medicine, Ulsan University Hospital, South Korea—We examined whole blood (MnB), red blood cell (MnRBC), plasma (MnP) and urinary Mn (MnU) concentrations in 22 liver cirrhotics and 10 healthy controls to evaluate Mn concentration in which a fraction of biological samples best reflects pallidal signal intensities (pallidal index; PI) on T1‐weighted magnetic resonance images (MRI) in liver cirrhotics. Increased signal intensity in the globus pallidus was observed in 18 (81.8%) of the 22 patients with liver cirrhosis. In a transplanted patient, increased pallidal signals also resolved as his liver function tests normalized after liver transplantation. There were significant correlations between MnB/MnRBC and PI (ρ=0.529, ρ=0.573, respectively) in liver cirrhotics, although no significant correlation was observed between MnP/MnU and PI. According to a multiple linear regression, MnB and MnRBC reflected the signal intensities of T1‐weighted MRI better than MnP or MnU.

Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy for HBeAg positive chronic hepatitis B.

Summary.  The aim of this study was to determine whether the changing patterns of quantitative hepatitis B e antigen (HBeAg) levels by serial monitoring could predict HBeAg seroconversion and viral breakthrough during lamivudine therapy. We retrospectively analysed 340 HBeAg positive naïve chronic hepatitis B patients treated with lamivudine. The mean duration of lamivudine therapy was 18.7 (range 6–56) months. The changing patterns and reduction rates of pretreatment HBeAg levels by serial monitoring were categorized into three groups: Decrescendo group (n = 195), Decrescendo‐crescendo group (n = 65) and no changing or fluctuating group (n = 80). Of 109 patients who had achieved HBeAg seroconversion, 105 (96.3%) were included in the decrescendo group. The decrescendo group, pretreatment quantitative HBeAg levels, alanine aminotransferase levels, and the duration of lamivudine therapy were independent predictive factors for HBeAg seroconversion. Of 82 patients who had viral breakthrough, 53 (64.6%) were in the decrescendo‐crescendo group and 21 (25.6%) were in the no changing or fluctuating group. The only predictive factor for viral breakthrough was the changing patterns of quantitative HBeAg levels, especially, the decrescendo‐crescendo group and the no changing or fluctuating group. The mean time of turning points in the decrescendo‐crescendo group was 7.1 months earlier than the mean time of viral breakthrough (9.0 months vs 16.5 months). Therefore, the changing patterns of quantitative HBeAg levels by serial monitoring during lamivudine therapy may allow not only the prediction of treatment responses, but also an early recognition of a viral breakthrough.

Characteristic clinical features of hepatocellular carcinoma associated with Budd-Chiari syndrome: evidence of different carcinogenic process from hepatitis B virus-associated hepatocellular carcinoma.

Objective Budd–Chiari syndrome (BCS) is a known risk factor for hepatocellular carcinoma (HCC). Considering the pathophysiological mechanism of BCS, BCS-associated HCC may have a different carcinogenic process to hepatitis B virus (HBV)-associated HCC, resulting in different characteristic clinical features. Methods The clinical, radiological and histopathological characteristics of 15 HCCs associated with BCS were analysed and compared with 211 HBV-associated HCCs. Results HCC associated with BCS showed a female predominance in contrast to a male predominance in HCC associated with HBV infection. Child classes of BCS-associated HCC patients were not different from the classes of HBV-associated HCC. BCS tended to be associated with the single nodular type of HCC. Only one BCS-associated HCC patient had portal vein invasion at the time of diagnosis, compared with 96 patients with HBV-associated HCC. No HCC patients with BCS showed biliary invasion, compared with 47 HBV-associated HCC patients. The median survival period of HCC patients associated with BCS was 58 months, which was much longer than the median survival period of 10 months in HBV-associated HCC. All of the three BCS-associated HCCs available for histological examination were well differentiated. Conclusions Patients with HCC associated with BCS seemed to survive for much longer periods than those with HBV due to the low invasiveness of the tumour. Such unique clinical features may be evidence of different carcinogenic processes in BCS-associated and HBV-associated HCC.