Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

Vigorous Periprocedural Hydration With Lactated Ringer's Solution Reduces the Risk of Pancreatitis After Retrograde Cholangiopancreatography in Hospitalized Patients.

BACKGROUND & AIMS: Vigorous intravenous fluid resuscitation (IVFR) was reported to reduce post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in a pilot study. We performed a randomized, double-blind controlled trial to establish whether periprocedural vigorous IVFR reduces the risk of post-ERCP pancreatitis. METHODS: A total of 510 patients with native papilla at 3 tertiary referral centers in Korea were randomly assigned (1:1) to groups given vigorous IVFR (lactated Ringer's solution in an initial bolus of 10 mL/kg before the procedure, 3 mL/kg/h during the procedure, for 8 hours after the procedure, and a post-procedure bolus of 10 mL/kg) or a standard IVFR (lactated Ringer's solution at 1.5 mL/kg/h during and for 8 hours after the procedure). The primary end point of the study was the development of post-ERCP pancreatitis, and the secondary end point was severity of pancreatitis, hyperamylasemia, and fluid overload. RESULTS: The main indications for ERCP were choledocholithiasis (58%) and malignant biliary stricture (27%). Post-ERCP pancreatitis developed in 11 patients in the vigorous IVFR group (4.3%) and 25 patients in the standard IVFR group (9.8%) (relative risk, 0.41; 95% CI, 0.20-0.86; P = .016). Moderate or severe acute pancreatitis occurred in a significantly smaller proportion of patients in the vigorous IVFR group (0.4%) than in the standard IVFR group (2.0%; P = .040). One patient in the vigorous IVFR group developed peripheral edema. CONCLUSIONS: In a double-blind, randomized controlled trial, we found vigorous periprocedural intravenous hydration with lactated Ringer's solution to reduce the incidence and severity of post-ERCP pancreatitis in average-risk and high-risk cases. IVFR is not associated with increased adverse events. ClinicalTrials.gov number: NCT02308891.

Impact of antiviral therapy on hepatocellular carcinoma and mortality in patients with chronic hepatitis C: systematic review and meta-analysis.

BACKGROUND: The long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and mortality according to the response to antiviral therapy. This study aimed to assess the impact of antiviral treatment on the development of HCC and mortality in patients with chronic HCV infection. METHODS: A systematic review was conducted for studies that evaluated the antiviral efficacy for patients with chronic hepatitis C or assessed the development of HCC or mortality between SVR (sustained virologic response) and non-SVR patients. The methodological quality of the enrolled publications was evaluated using Risk of Bias table or Newcastle-Ottawa scale. Random-effect model meta-analyses and meta-regression were performed. Publication bias was assessed. RESULTS: In total, 59 studies (4 RCTs, 15 prospective and 40 retrospective cohort studies) were included. Antiviral treatment was associated with reduced development of HCC (vs. no treatment; OR 0.392, 95% CI 0.275-0.557), and this effect was intensified when SVR was achieved (vs. no SVR, OR: 0.203, 95% CI 0.164-0.251). Antiviral treatment was associated with lower all-cause mortality (vs. no treatment; OR 0.380, 95% CI 0.295-0.489) and liver-specific mortality (OR 0.363, 95% CI 0.260-0.508). This rate was also intensified when SVR was achieved [all-cause mortality (vs. no SVR, OR 0.255, 95% CI 0.199-0.326), liver-specific mortality (OR 0.126, 95% CI 0.094-0.169)]. Sensitivity analyses revealed robust results, and a small study effect was minimal. CONCLUSIONS: In patients with chronic hepatitis C, antiviral therapy can reduce the development of HCC and mortality, especially when SVR is achieved.

Clinical outcomes of patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective study of routine clinical practice in multi-institutions.

BACKGROUND: Sorafenib is an orally administered multikinase inhibitor with antiangiogenic and antiproliferative properties. The results of large clinical trials demonstrate that sorafenib prolongs survival and the time to progression of patients with advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the outcomes of such patients who were routinely treated with sorafenib at multi-institutions in Korea, in contrast to formal clinical trials. METHODS: Between August 2007 and March 2012, patients with advanced HCC in seven referral medical centers in Daejeon-Chungcheong Province of Korea were retrospectively enrolled to evaluate treatment response, survival, and tolerability following administration of sorafenib. The treatment response was assessed in accordance with the Response Evaluation Criteria in Solid Tumor 1.1 guidelines. RESULTS: Among 116 patients, 66 (57%) had undergone treatment for HCC, and 77 (66%) were accompanied with Child-Pugh A cirrhosis. The median duration of sorafenib treatment was 67 days (range 14-452 days). Median overall survival and median time to progression were 141 days and 90 days, respectively. Complete response, partial response, and stable disease were achieved for 0%, 2%, and 29% of patients, respectively. Overall median survival, but not the median time to progression, was significantly shorter for patients with Child-Pugh B cirrhosis compared with those with Child-Pugh A cirrhosis (64 days vs 168 days, P = 0.004). Child-Pugh B cirrhosis (P = 0.024) and a high level of serum alpha-fetoprotein (P = 0.039) were independent risk factors for poor overall survival. Thirty-nine (34%) patients experienced grade 3/4 adverse events such as hand-foot skin reactions and diarrhea that required dose adjustment. CONCLUSIONS: The clinical outcomes of sorafenib-treated patients with advanced HCC were comparable to those reported by formal clinical trial conducted in the Asia-Pacific region. Underlying hepatic dysfunction was the most important risk factor for shorter survival.

Nonalcoholic steatohepatitis associated with metabolic syndrome: relationship to insulin resistance and liver histology.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome. We aimed to assess the relationship of metabolic syndrome-associated NASH and insulin resistance (IR), and to define the correlation of chemicometabolic components with different degree of liver histology in NASH subjects. STUDY: Ninety-four subjects with NASH (mean age, 38±14 y; 77% male) were enrolled. IR was calculated using a homeostasis model assessment of insulin resistance (HOMA-IR). Clinical characteristics including IR and accompanying metabolic risk components in NASH subjects were compared with those of 52 diabetics and 21 healthy controls. The relationship between IR and chemicometabolic variables was analyzed according to different clustering of metabolic risk components and the histologic activity. RESULTS: NASH subjects had a stronger association with metabolic syndrome than healthy controls. HOMA-IR was significantly higher in NASH subjects than in healthy controls (4.4±2.5 vs. 1.7±0.6; P<0.001) but not than in diabetics. NASH subjects with metabolic syndrome were more likely to have higher HOMA-IR compared with that of NASH subjects without metabolic syndrome (5.0±2.9 vs. 3.6±1.7; P=0.032). HOMA-IR showed a positive correlation with body mass index (r=0.428, P=0.015) and serum fasting blood sugar (r=0.365, P=0.037). Serum aspartate aminotransferase/alanine aminotransferase ratio (P=0.029) and high-density lipoprotein cholesterol level (P=0.034) were significantly affected according to the degree of fibrotic activity in 41 histology-proven NASH subjects. CONCLUSIONS: NASH subjects showed increased IR with a significant association of metabolic syndrome. The severity of hepatic fibrosis revealed a strong correlation with serum aspartate aminotransferase/alanine aminotransferase ratio and high-density lipoprotein cholesterol level.

Incremental value of cell block preparations over conventional smears alone in the evaluation of EUS-FNA for pancreatic masses.

BACKGROUND/AIMS: The effectiveness of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established for a definite pathological diagnosis of pancreatic solid masses. We investigated the usefulness of cell block preparations in EUS-FNA, by evaluating the added value of cell block preparations over conventional smears alone. METHODOLOGY: Between March 2011 and June 2013, 61 patients were retrospectively evaluated who underwent EUS-FNA for pancreatic solid masses. Diagnostic values for diagnosing pancreatic malignancy were compared for a combination of the conventional smear and cell block (CSCB) and the conventional smear alone (CS). RESULTS: The addition of the cell block technique increased the sensitivity of conventional smear for diagnosing the pancreatic malignancy from 79% (CS) to 90% (CSCB, p=0.0313) and the accuracy from 81% to 91% (p=0.0313). The specificity and positive predictive value were 100% in both methods. The negative predictive value was increased from 33% (CS) to 50% (CSCB), but this difference was not statistically significant (p=0.0833). CONCLUSION: The addition of the cell block method after a conventional smear may increase the sensitivity and negative predictive value for diagnosing the pancreatic malignancy in patients with pancreatic masses who undergo EUS-FNA. Further study may be warranted to determine whether the cell block method can replace the conventional smear.

Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma.

UNLABELLED: Primary liver cancer is the third most common cause of cancer-related death worldwide, with a rising incidence in Western countries. Little is known about the genetic etiology of this disease. To identify genetic factors associated with hepatocellular carcinoma (HCC) and liver cirrhosis (LC), we conducted a comprehensive, genome-wide variation analysis in a population of unrelated Asian individuals. Copy number variation (CNV) and single nucleotide polymorphisms (SNPs) were assayed in peripheral blood with the high-density Affymetrix SNP6.0 microarray platform. We used a two-stage discovery and replication design to control for overfitting and to validate observed results. We identified a strong association with CNV at the T-cell receptor gamma and alpha loci (P < 1 × 10(-15)) in HCC cases when contrasted with controls. This variation appears to be somatic in origin, reflecting differences between T-cell receptor processing in lymphocytes from individuals with liver disease and healthy individuals that is not attributable to chronic hepatitis virus infection. Analysis of constitutional variation identified three susceptibility loci including the class II MHC complex, whose protein products present antigen to T-cell receptors and mediate immune surveillance. Statistical analysis of biologic networks identified variation in the "antigen presentation and processing" pathway as being highly significantly associated with HCC (P = 1 × 10(-11)). SNP analysis identified two variants whose allele frequencies differ significantly between HCC and LC. One of these (P = 1.74 × 10(-12)) lies in the PTEN homolog TPTE2. CONCLUSION: Combined analysis of CNV, individual SNPs, and pathways suggest that HCC susceptibility is mediated by germline factors affecting the immune response and differences in T-cell receptor processing.

Ruptured duodenal varices arising from the main portal vein successfully treated with endoscopic injection sclerotherapy: a case report.

Duodenal varices result from retroperitoneal portosystemic shunts that usually come from the pancreaticoduodenal vein and drain into the inferior vena cava. Because they are a rare but fatal cause of gastrointestinal bleeding, a prompt hemostatic intervention is mandatory. A 62-year-old man who had a history of excessive alcohol consumption presented with massive hematemesis and melena. Emergent endoscopy revealed ruptured varices with an adhering whitish fibrin clot on the postbulbar portion of the duodenum. Abdominal computed tomography demonstrated a cirrhotic liver with venous collaterals around the duodenum and extravasated contrast in the second and third portions. The collaterals originated from the main portal vein and drained via the right renal vein into the inferior vena cava. Endoscopic injection sclerotherapy with cyanoacrylate was successful in achieving hemostasis, and resulted in the near eradication of duodenal varices at a 6-month follow-up.

Cystic Primary Hepatic Neuroendocrine Tumor.

Neuroendocrine tumors (NETs) can arise throughout the body. Most NETs in the liver are metastatic tumors; primary hepatic NET (PHNET) is extremely rare. A diagnosis of PHNET is very difficult. No single modality can diagnose PHNET by itself, and it often resembles other hypervascular masses of the liver. This paper reports the case of a 51-year old female with a large hepatic mass. Unlike most of PHNETs reported previously, it was composed of a solid mass with mainly multiple cystic lesions, which led to an erroneous diagnosis of hepatic mucinous cystadenoma or cystadenocarcinoma. PHNET with cystic lesions is extremely rare, and the features are not well studied. This case may help physicians suspect PHNET in a differential diagnosis of an atypical hepatic mass.

The clinical impact of gut microbiota in chronic kidney disease.

Gut microorganisms play critical roles in both maintaining host homeostasis and the development of diverse diseases. Gut dysbiosis, an alteration of the composition and function of gut microorganisms, is commonly seen in patients with chronic kidney disease (CKD). CKD itself contributes to a disruption of the symbiotic relationship between the gut microbiota and the host, while the resulting gut dysbiosis may play a part in stage progression of CKD. This bidirectional relationship supports the concept that the gut microbiota is considered a novel focus for the pathogenesis and management of CKD. This article examines the interaction between the gut microbiota and the kidney, the mutual effects of dysbiosis and CKD, and possible treatment options to restore gut eubiosis, and reduce CKD progression and its related complications.

Clinical Patterns and Outcome of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) may develop into liver cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to compare the clinical patterns and survival outcomes of NAFLD-related HCC patients and those of alcoholic liver disease (ALD)-related or hepatitis B virus (HBV)-related HCC patients. Methods: A total of 622 HCC patients with associated NAFLD (n = 56), ALD (n = 173), or HBV infection (n = 393) were enrolled. The clinical characteristics and survival were analyzed according to the underlying liver diseases. Results: NAFLD-related HCC patients were more commonly older women and had more metabolic risk factors but were less likely to have cirrhosis and ascites, compared to ALD-related or HBV-related HCC patients. NAFLD-related HCC more often had an infiltrative pattern (P=0.047), a larger tumor (P=0.001), more macrovascular invasion (P=0.022), and exceeded the Milan criteria (P=0.001), but was less frequently diagnosed during tumor surveillance (P=0.025). Survival analysis did not show any difference among NAFLD-related, ALD-related, and HBV-related HCC patients. Furthermore, propensity score matching analysis did not reveal a significant difference in the median survival between the different groups (NAFLD vs. ALD, 14.0 months [95% confidence interval (CI), 2.0-26.0] vs. 13.0 months [95% CI, 0-26.3]; P=0.667, NAFLD vs. HBV, 14.0 months [95% CI, 2.0-26.0] vs. 12.0 months [95% CI, 4.3-17.8]; P=0.573). Conclusions: NAFLD-related HCCs were more often detected at an advanced stage with infiltrative patterns, although they showed no significant difference in survival compared to ALD-related or HBV-related HCCs. A future prospective research should be focused on identifying NAFLD patients who require strict surveillance in order to early detect and timely treat HCC.

Perception and attitudes of medical students on clinical clerkship in the era of the Coronavirus Disease 2019 pandemic.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) has been placing severe strain on global healthcare systems and medical education programs, leading to growing demands for medical students to assume the role of preliminary healthcare providers. OBJECTIVES: To assess the perception and attitudes of medical students about clinical clerkship training during the COVID-19 pandemic. DESIGN: A cross-sectional survey with web-based 3-fields/14-items questionnaire was conducted, from April 7 to 14, 2020, to evaluate their self-assessed perception and attitudes on clerkship training of hospital practice under the COVID-19 outbreak and spread among 161 (78 on pre-clerkship course, 83 on clinical clerkship course) medical students at Dankook University College of Medicine, Cheonan, Republic of Korea. RESULTS: Of the 151 medical students who completed the survey, 81 students (53.7%) considered themselves familiar with COVID-19. Although the students were concerned about the spread of the virus during clinical clerkship training, 118 (78.1%) students preferred the clerkship training in a hospital practice. The students in the clinical clerkship program preferred this over those in the pre-clerkship program (85.7% vs. 70.2%, P = 0.03), primarily because a clinical clerkship could not be replaced by an online class during the COVID-19 pandemic. In addition, their responses indicated, in order of significance, fear of not completing the clerkship course on time, willingness to participate as a preliminary healthcare provider in pandemic, the potential waste of tuition, and belief that a hospital is rather safe. The change in the academic calendar had not a positive impact on the lifestyles of many students. CONCLUSIONS: In circumstances such as the COVID-19 pandemic, educational strategies to clinical clerkship training for medical students should be developed to provide them with the opportunity to be actively involved in hospital practice under strict safety guidance focused on preventing virus infection and transmission.

Phlebosclerotic colitis in a cirrhotic patient with portal hypertension: the first case in Korea.

Phlebosclerotic colitis is a rare form of ischemic colitis characterized by the thickening of the wall of the affected colon due to fibrous degeneration of submucosal layer of colon and fibrotic obstruction of the colono-mesenteric vein, resulting in the disturbance of venous return from the colon. The pathogenic mechanism of this entity remains unknown but chronic liver disease with portal hypertension is maybe thought to be one of the speculated mechanisms. Here we first report the case of surgically confirmed phlebosclerotic colitis, that was in the early stage but showed the aggressive nature, in a 61-yr-old cirrhotic patients with portal hypertension in Korea.

Molecular targeting for treatment of advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major global health problem, which has a grave morbidity and mortality. Over the past few decades, no effective systemic therapeutic modalities have been established for patients with the unresectable HCC in advanced stage. Sorafenib is a small molecule that blocks cancer cell proliferation by targeting the intracellular signaling pathway at the level of Raf-1 and B-Raf serine-threonine kinases, and exerts an anti-angiogenic effect by targeting the vascular endothelial growth factor receptor-1, 2 and 3, and platelet-derived growth factor receptor-beta tyrosine kinases. Recently, two clinical successful applications, SHARP and Asia-Pacific trial, of multikinase inhibitor sorafenib represent a significant advance in the treatment of advanced HCC patients without a curative chance. However, because the results of clinical trials show diverse responses in a subset of HCC patients, a molecular classification of HCC through the excavation of specific biomarkers related to its biological behavior is necessary for sorting HCC patients to each group with a biological homogeneity, ultimately leading to the most suitable individualization of molecular targeted therapy in HCC.

Current status of liver diseases in Korea: hepatocellular carcinoma.

Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. During the last two decades, the incidence rate of primary liver cancer has shown a modest decrease, but its mortality rate has slightly increased. The incidence of HCC, according to age, peaks in the late sixth decade in men and in the early seventh decade in women. Hepatitis B virus (HBV) is the most important risk factor, which represents approximately 70% of all HCC, and hepatitis C virus (HCV) and alcohol are the next in order of major risk factors for the development of HCC in Korea. HBV-associated HCC occurs 10 years earlier than HCV-associated HCC due to a more prolonged exposure to HBV, which is vertically transmitted almost from HBsAg-positive mother in HBV-endemic area. National Cancer Control Institute, which was reorganized in 2005, is now working for several national projects such as National Cancer Registration Program, National R&D Program for Cancer Control and National Cancer Screening Program. International collaboration for the clinico-epidemiologic research would be needed to provide the specific measures for managing HCC in diverse etiologic situations. Finally, the mechanisms of hepatitis virus-associated hepatocellular carcinogenesis might be clarified to provide insights into the advanced therapeutic and preventive approaches for HCC in Korea, where the majority of HCC originate from chronic HBV and HCV infections.

[A case of hepatocellular carcinoma presented as a huge intrahepatic hematoma].

Spontaneous intrahepatic bleeding is a rare condition. In the absence of trauma, intrahepatic hematoma may be due to underlying liver disease. We report a case of hepatocellular carcinoma in the patient who had huge intrahepatic hematoma without definite intrahepatic tumor at the time of initial presentation. A 54-year-old man was admitted to our hospital with a sudden onset of upper abdominal pain. Initial abdominal CT scan showed huge hematoma measuring more than 13 cm in diameter in the right lobe of the liver. However, there was no enhancing lesion in the liver. Laboratory data showed high alanine aminotransferase, alpha-fetoprotein and positive HBsAg. The MRI and angiography could not also depict any mass in the liver. The patient was treated with percutaneous drainage on the intrahepatic hematoma. The cytology from drainaged blood revealed no malignant cell. After hematoma decreased, follow-up CT scan depicted an enhancing tumor in the liver. He underwent right hepatic lobectomy and histopathological examination showed hepatocellular carcinoma.

[Clinical, radiological and pathological exploration of focal nodular hyperplasia of liver reported in Korea].

BACKGROUND/AIMS: Focal nodular hyperplasia (FNH) is mandatory to be differentiated from other hepatic tumorous conditions such as hepatocellular carcinoma and adenoma. The purpose of this study was to explore the clinical, radiological and pathological features of FNH cases reported in Korea. METHODS: We have searched the journals from the web site "http://koreamed.org" using keywords "focal nodular hyperplasia" and "liver" - total of 38 cases of FNH, 37 cases from 17 published articles and one case from our experience confirmed histologically, were reviewed and analyzed. RESULTS: Thirty eight cases were diagnosed between gestational age of 36 weeks and 67 years. Seventeen female patients (45%) had no history of taking oral contraceptives. Twenty cases (52.6%) experienced clinical symptoms such as abdominal pain and palpable mass. Computed tomography revealed contrast-enhancement in 34 nodules (85%) and typical central stellate scar in 9 (22.5%) of 40 nodules. Magnetic resonance imaging showed T1 weighted low signal in 18 (60%) and T2 weighted high signal in 22 (73.3%) of 30 nodules. Six (60%) of 10 cases showed hypervascular staining on hepatic angiography. Among 38 cases, 32 (84.2%) cases had single nodule and their mean size was 3.9 cm (0.5-16 cm). Pathologically, fibrous septa, proliferation of bile ductules and arterial wall thickening were seen in most cases. CONCLUSIONS: Of all the FNH cases reported in Korea, there were some differences in clinical aspects of sex ratio, accompanying clinical symptoms, and relationship with oral contraceptives, compared with previous reports. Further prospective studies are needed by means of nation-wide clinical survey and analysis.

[Down-regulation of survivin in growth inhibition of hepatoma cells induced by a 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 micrometer), 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.

[Efficacy of initial treatment with peginterferon alpha-2a versus peginterferon alpha-2b in combination with ribavirin in naive chronic hepatitis C patients living in Daejeon and Chungcheong Province in Korea: a comparative study].

BACKGROUNDS/AIMS: Peginterferon alpha-2a or -2b is the standard treatment regimen in chronic hepatitis C. However, there have been few comparative studies of the efficacies of these two types of peginterferon. We evaluated their efficacies in combination with ribavirin as a initial treatment for chronic hepatitis C. METHODS: Ninety-seven patients were treated with peginterferon alpha-2a (180 microg/week, n=48) or peginterferon alpha-2b (1.5 microg/kg/week, n=49) plus ribavirin (800 mg/day for 24 weeks in genotype non-1 or 1,000-1,200 mg/day for 48 weeks in genotype 1). Virologic responses including the early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and adverse effects were analyzed retrospectively. RESULTS: The virologic response rates did not differ significantly between peginterferon alpha-2a and -2b: 89.6% and 89.7% for EVR, 79.2% and 79.5% for ETR, 72.9% and 73.5% for SVR, respectively. Analysis of the virologic responses according to genotype also revealed no significant differences in SVR between peginterferon alpha-2a and -2b (59.3% vs. 59.7% for genotype 1 and 90.5% vs. 83.3% for genotype non-1, respectively), or in adverse effects including flu-like symptom, rash, itching, neutropenia, and thrombocytopenia. CONCLUSIONS: We found no significant differences in therapeutic efficacies and adverse effects between the alpha-2a and -2b types of peginterferon as the initial treatment regimen in naive chronic hepatitis C patients.