Sang Wook Choi

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.

Polymorphism near the IL28B gene in Korean hepatitis C virus-infected patients treated with peg-interferon plus ribavirin

BACKGROUND Single nucleotide polymorphisms (SNPs) near the IL28B gene have recently been described as predictors of antiviral therapy responses in patients with hepatitis C virus (HCV) genotype-1. OBJECTIVES The aim of this study was to investigate the association between genetic variation near the IL28B gene and treatment outcome prediction in Korean patients receiving peg-interferon (PEG-IFN) plus ribavirin therapy. STUDY DESIGN The allelic discrimination assay by Taqman real-time PCR was developed to determine genotypes of SNPs, rs12979860 and rs8099917, which were analyzed in 65 Korean patients with HCV genotype-1. RESULTS For rs12979860, the frequency of patients with sustained virological response (SVR) was 70.2% in those with the CC genotype and 25% in those with the CT genotype. Early virological response (EVR) in patients with the CC genotype (84.2%) was higher than in those with the CT genotype (25.0%). For rs8099917, patients with the TT genotype showed significantly higher in SVR and EVR than those with the TG/GG genotype (69.6% vs 33.3% and 82.1% vs 44.4%, respectively). With regards to the genotype frequency of the SNPs, the homozygous genotypes for rs12979860 (CC) or rs8099917 (TT) in Korean patients showed a significantly higher frequency as compared with other ethnicities; Caucasians, African-American, Hispanic, and Japanese. CONCLUSIONS These results demonstrate that the genotypes rs12979860 CC and rs8099917 TT were more frequently observed in Korean patients compared to other ethnicities, and suggest that the genetic characteristics of patients may be prognostic factor that predicts antiviral response to PEG-IFN therapy for chronic hepatitis C.

Role of long-term lamivudine treatment of hepatitis B virus recurrence after liver transplantation.

In this study, the long‐term (>3 years) efficacy of combination therapy for hepatitis B virus (HBV) recurrence and the associated factors were investigated. One hundred and sixty‐five consecutive HBsAg‐positive patients (92 with liver cirrhosis, 73 with hepatocellular carcinoma; HCC) who underwent liver transplantation were assessed with a median follow‐up time of 40 months. One hundred and twenty‐one patients (121/165, 73.3%) were treated with lamivudine before transplantation for a mean of 8.4 months (range 0.1–72 months). The post‐transplantation treatment protocol consisted of a high dose intravenous hepatitis B immunoglobulin (HBIg) followed by a low dose intramuscular HBIg and lamivudine combination therapy. Seven (4.2%, 7/165) recipients experienced HBV recurrence at a median time of 19 months (range 5–36 months) following transplantation. Six of seven cases of HBV recurrence were treated with lamivudine before transplantation for a median period of 15 months (range 0.6–30 months). Eighteen (24.6%, 18/73) patients had HCC recurrences after transplantation. Of the four patients with both HCC and HBV recurrence, three experienced HBV recurrence after recurrence of HCC. The clinical factor associated with HBV recurrence in the total cohort (n = 165) was the duration of antiviral treatment (over 6 months) before transplantation (P = 0.004). In the HCC group, HCC recurrence after transplantation (P = 0.002), tumor burden before transplantation (P = 0.005), and postoperative adjuvant chemotherapy (P = 0.002), were additional factors for HBV recurrence. Combination therapy of HBIg and antiviral drugs was effective over 3 years regardless of the pretransplantation viral load. However, the possible recurrence of HBV needs to be monitored cautiously in patients treated with long‐term (over 6 months) lamivudine. J. Med. Virol. 80:1891–1899, 2008.

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease.

Background/Aims The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. Methods One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. Results According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. Conclusions Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.

Early virological response predicts outcome during extended lamivudine retreatment in patients with chronic hepatitis B who relapsed after initial HBeAg responses

Background and Aim:  Studies from hepatitis B virus endemic areas have shown less durable lamivudine‐induced responses and have raised issues about the management of a post‐treatment relapse.

Hepatitis B Virus Load in Serum Does Not Reflect Histologic Activity in Patients With Decompensated Cirrhosis

BACKGROUND & AIMS Little is known about whether histologic data can predict which patients with hepatitis B virus (HBV)-related decompensated cirrhosis will respond to antiviral therapies. We assessed the relationship between serum HBV DNA load and histologic activity by analyzing liver specimens from patients with decompensated cirrhosis. METHODS The study included 72 consecutive patients who underwent liver transplantation for HBV-related decompensated cirrhosis between November 2000 and March 2008. None of the patients had received nucleoside or nucleotide analogues more than 2 weeks before transplantation. Serum HBV DNA levels at the time of transplantation were compared with histologic activity in explanted liver specimens. RESULTS The median HBV DNA level of the 72 patients was 5.40 log(10) copies/mL (range, 1.45-8.00 log(10) copies/mL). There were no differences in HBV DNA level between patients grouped according to lobular or portoperiportal activity (P = .678, P = .291, respectively). Of 16 patients (22.2%) with HBV DNA levels less than 2000 copies/mL, 8 patients (50.0%) had moderate or severe portoperiportal activity; their median alanine aminotransferase level was 30.5 U/L (range, 12-135 U/L). CONCLUSIONS HBV DNA load does not reflect histologic activity in patients with HBV-related decompensated cirrhosis. Although patients with decompensated cirrhosis might have normal levels of alanine aminotransferase and a low level of viremia (<2000 copies/mL), they still can have significant portoperiportal activity.

Subgenotype and genetic variability in the precore/core regions of hepatitis B virus in Korean patients with chronic liver disease.

Objective: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) subgenotypes, the spectrum of mutations in the precore/core region through phylogenetic analysis, and the relevance of viral characteristics in disease progression in Korean patients. Methods: 133 patients with chronic HBV infection were enrolled. The precore and core region of HBV was amplified and sequenced. Phylogenetic analysis was performed for subgenotyping and the changes of nucleotides and amino acid were compared in liver disease stages. Results: HBV/C2 subgenotype was predominant in chronic HBV carriers (98.5%), followed by HBV/A2 (0.75%) and HBV/C7 (0.75%). The mutations of the precore region were not different between liver disease stages. However, amino acid changes in the cytotoxic T lymphocyte epitope (p < 0.020), CD4+ T cell epitope (p < 0.027), or B cell epitope (p < 0.029) were significantly higher in liver cirrhosis patients than in chronic hepatitis patients, but not in hepatocellular carcinoma patients. Conclusion: HBV/C2 is the most prevalent subgenotype in Korea, and HBV/C7 subgenotype found in the Philippines was first identified in the Korean population. Mutations in immune epitopes within the core gene were significantly associated with disease progression.

Ultrastructural Changes of Hepatic Stellate Cells in the Space of Disse in Alcoholic Fatty Liver

Background : Hepatic stellate cell (HSC) has been suggested to play a role in fibrogenesis in alcoholic liver disease. We evaluate the correlation with fibrogenesis and ultrastructure of hepatic stellate cells in alcoholic fatty liver. Methods : We studied 6 patients with alcoholic fatty liver and 5 non-alcoholic fatty liver. The numbers of fat droplets in hepatic stellate cell was determined by electron microscopy. We also studied the grading of deposition of collagen fibers in the space of Disse. We were to evaluate the structure of hepatic stellate cells in the space of Disse by light and electron microscopy. Results : Wider distribution of fat droplets in hepatic stellate cells in alcoholic fatty liver than in normal liver. The hypertrophied endoplasmic reticulum in hepatic stellate cells is a prominent findings in alcoholic fatty liver. We observed basement membrane-like materials in patients with alcoholic fatty liver with hepatic fibrosis. Conclusion : The results demonstrate that, in patients with alcoholic fatty liver by alcoholic liver injury, the hepatic stellate cells may play an important role in the fibrogenesis of perisinusoidal spaces in the liver.

A Case of Ulcerative Colitis Following Acute Hepatitis Induced by Epstein-Barr Virus Infection

Epstein-Barr virus (EBV) infection varies in its clinical manifestations and severity. EBV can be a causative agent of hepatitis and may have a role in the pathogenesis of chronic autoimmune diseases including inflammatory bowel disease. A 24-year-old woman was admitted to our hospital, presenting with fever and elevated liver enzymes. She was diagnosed with acute hepatitis and EBV infection according to serologic tests and liver biopsy. Within two months, she was re-admitted to our hospital, presenting with hematochezia and lower abdominal pain. She was diagnosed with ulcerative colitis. In situ hybridization for EBV was positive in initial liver biopsy and colon biopsy. Here we report an unusual case of acute EBV hepatitis followed at a short interval by ulcerative colitis.