Preservation of a traditional Korean dietary pattern and emergence of a fruit and dairy dietary pattern among adults in South Korea: secular transitions in dietary patterns of a prospective study from 1998 to 2010.

Transitions in nutrition patterns tend to emerge through industrialization and economic development. We hypothesized that the dietary patterns among South Korean adults who were 20 years or older have changed significantly from 1998 to 2010. Herein, a repeated cross-sectional analysis of data was followed for 140601 adults. We noted changes in consumption, after adjusting for age, sex, body mass index, and exercise, and tested the trends across the study period. Factor and cluster analyses were used to derive dietary patterns. A decrease in traditional Korean food consumption, including cereals, vegetables (252-176 g), and Kimchi (127-82 g), occurred, whereas fruit (172-252 g), egg, and fried food intakes increased (P < .05). Total daily energy intake declined steadily from 1931 in 1998 to 1691 kcal in 2010. Carbohydrate intakes were unchanged over the study period; however, fat-derived energy intake increased slightly from 19.7% to 20.0% (P < .05). Our factor and cluster analyses identified 3 dietary patterns: "Korean" diet (rice, vegetables, and Kimchi), "Western" diet (soda, eggs, and oil), and "New" diet (low sugar and high fruit and dairy product intakes). Compared to 1998, approximately 40% of participants still followed a Korean diet in 2010. Interestingly, the popularity of the Western diet fell by approximately 20%, whereas the new diet pattern increased 2-fold over the study period. Overall, these data show secular trends in dietary patterns that included a preservation of the traditional Korean diet and the emergence of a new diet pattern, and it demonstrated a unique transition in food and nutrient intakes in Korea.

Serum uric acid and chronic kidney disease: the Severance cohort study.

BACKGROUND: Both serum uric acid (SUA) and chronic kidney disease (CKD) are associated with the risk of cardiovascular disease; however, it is unclear whether SUA independently increases the risk of CKD based on longitudinal data. METHODS: To investigate the relationship between SUA levels and CKD development, we initiated a 10.2-year prospective cohort study. Data from 14 939 Koreans, 20-84 years of age, who completed a questionnaire and medical examination at the Severance Health Promotion Center were evaluated. The outcome of interest, CKD, was defined as an estimated glomerular filtration rate (GFR) of <60 mL/min/1.73m(2) via the simplified Modification of Diet in Renal Disease equation. RESULTS: A multivariate Cox proportional hazard model, controlling for age, life style and other cardiovascular risk factors, showed an increased risk of developing CKD for men [hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.9] and women (HR = 1.3; 95% CI = 1.0-1.8) in the highest quartiles of SUA compared to their counterparts in the lowest quartiles. The relationship between SUA and CKD was linear and stepwise in men. The HRs for renal function Grade 2 (75-89.9 mL/min/1.73m(2)), Grade 3 (60-74.9 mL/min/1.73m(2)) and Grade 4 (<60 mL/min/1.73m(2)) increased with an increase in SUA quartiles as compared to the baseline GFR group (Grade 1, ≥90 mL/min/1.73m(2)). CONCLUSIONS: Higher SUA levels increased the risk of CKD, suggesting that at least part of the reported association between SUA and cardiovascular disease may be connected to CKD.

Recombinant interferon-Beta-1alpha plus ribavirin for the treatment of chronic HCV infection: a prospective, randomized, comparative pilot study.

BACKGROUND/AIMS: Interferon beta (IFN-beta) has been shown to have antiviral activity, and thus could be useful in treating viral infections. Therefore, we compared the efficacy and safety of recombinant IFN-beta (IFN-beta-1a) plus oral ribavirin versus interferon alpha (IFN-alpha) plus ribavirin therapy for the treatment of chronic hepatitis C (HCV). METHODS: Twenty treatment-naïve patients were randomized into two equal-sized treatment groups. Both IFN-beta-1a (44 microg) and IFN-alpha (3 MIU) were given subcutaneously three times a week, while ribavirin was given orally at 1,000-1,200 mg/day. Patients were treated for 24 weeks and followed for an additional 24 weeks. RESULTS: After 24 weeks of treatment, six (60%) and four patients (40%) in the IFN-beta-1a group and IFN-alpha groups, respectively, achieved viral clearance. The sustained virological response (SVR) at the end of the observation period was similar in both groups (40%). However, the baseline viral load was significantly higher (p=0.034) in the IFN-beta-1a group than in the IFN-alpha group, and there were more HCV genotype 1 patients in the IFN-beta-1a group (eight versus seven). The IFN-beta-1a group was associated with similar adverse events in terms of frequency and severity. CONCLUSIONS: The SVR rate and safety profile were similar for the combination of IFN-beta-1a and ribavirin and that of IFN-alpha and ribavirin.

Combination therapy of thymosin alpha-1 and lamivudine for HBeAg positive chronic hepatitis B: A prospective randomized, comparative pilot study.

BACKGROUND AND AIM: Monotherapy of lamivudine, interferon-alpha (IFN-alpha), and thymosin alpha-1 (Talpha1) is unlikely to be sufficient for the eradication of a chronic hepatitis B virus (HBV) infection. The aim of our study is to elucidate whether the combination of Talpha1 and lamivudine is superior to lamivudine monotherapy in hepatitis B e antigen (HBeAg) positive naïve patients with chronic hepatitis B. METHODS: Sixty-seven patients were assigned to two different groups in a randomized manner. The combination group (n = 34) received Talpha1 (1.6 mg subcutaneously, twice a week) and lamivudine (100 mg orally, daily) for 24 weeks, followed by continuous lamivudine therapy. The monotherapy group (n = 33) received lamivudine monotherapy continuously. RESULTS: The incidence of HBeAg seroconversion at 24 weeks was 26.5% (9/34) in the combination group and 6.1% (2/33) in the monotherapy group (P = 0.024). However, there was no statistically significant difference between 26.5% (9/34) in the combination group and 12.1% (4/33) in the monotherapy group at 52 weeks (P = 0.138). The emergence of viral breakthrough gradually increased to 35.3% (12/34) in the combination group, and to 21.2% (7/33) in the monotherapy group at 52 weeks (P = 0.201). CONCLUSIONS: The combination treatment of Talpha1 and lamivudine did not have an obvious benefit of virological and biochemical response as compared to the lamivudine monotherapy during the combination period. In addition, after the cessation of Talpha1 treatment, the combination therapy did not prevent the occurrence of viral and biochemical breakthroughs.

Prediction of microvascular invasion before curative resection of hepatocellular carcinoma.

BACKGROUND: The accurate staging of hepatocellular carcinoma (HCC) is important in establishing treatment strategies and prognosis. Among tumor factors, microvascular invasion, one of TNM staging components and prognostic factors, is underestimated preoperatively, due to inaccuracy of imaging modalities. We investigated preoperative predictors of microvascular invasion. METHODS: We reviewed 190 consecutive HCC patients given curative resection from 1999 to 2006. All were treatment-naive and monitored every 3 months after resection. Tumor recurrence, survivals, and clinicopathological factors associated with microvascular invasion were analyzed. RESULTS: The 5-year disease-free survival (DFS) rate was 39.4%(median follow-up duration: 35 months). On resection pathology, 38.9% (74/190 patients) had microvascular invasion undetected preoperatively, using liver spiral computed tomography (CT) or angiography. Independent predictors of microvascular invasion were tumor size (P = 0.043), number (P = 0.011), and Edmondson grade (P = 0.001). Patients with Edmondson grade 1 and size <5 cm had no microvascular invasion, while those with grade > or =2 had higher incidences (7/18 patients, 38.8%) even in small tumor (<2 cm). When tumors recurred, presence of microvascular invasion independently increased incidences of multiple tumors, portal vein invasion, and diffuse-infiltrative patterns significantly. CONCLUSIONS: Preoperative predictors of microvascular invasion are tumor size, number, and Edmondson grade, which may be useful for making clinical decisions in both non-surgical and surgical candidates.

Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection.

BACKGROUND: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence. PATIENTS AND METHODS: We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow-up), fluctuating DNA (cut-off value: 100,000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non-viraemia group) had consistently negative DNA (<100,000 copies/ml), while 68 (viraemia group) had consistently positive DNA (>100 000copies/ml). Serum DNA level, biochemical tests, alpha-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery. RESULTS: There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow-up duration between the two groups. During follow-up (median: 35 months), patients in the non-viraemia group had a lower 5-year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P=0.043). In multivariate analysis, sustained viraemia (P=0.041) increased recurrence independently. CONCLUSIONS: Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA.

Telbivudine versus lamivudine in patients with chronic hepatitis B.

BACKGROUND: Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B. METHODS: In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. RESULTS: At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7% vs. 56.3%, P=0.01); telbivudine also was not inferior to lamivudine for these end points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients, telbivudine was superior to lamivudine with respect to the mean reduction in the number of copies of HBV DNA from baseline, the proportion of patients with a reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of resistance to the drug. Elevated creatine kinase levels were more common in patients who received telbivudine, whereas elevated alanine aminotransferase and aspartate aminotransferase levels were more common in those who received lamivudine. CONCLUSIONS: Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine. (ClinicalTrials.gov number, NCT00057265 [ClinicalTrials.gov].).

[The efficacy and safety of telbivudine in korean patients with chronic hepatitis B].

BACKGROUND AND AIMS: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. METHODS: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. RESULTS: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. CONCLUSIONS: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.

[Clinical features and treatment outcome of advanced hepatocellular carcinoma with inferior vena caval invasion or atrial tumor thrombus].

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) with an extension to the inferior vena cava (IVC) or right atrium is uncommon, and its prognosis remains unclear due to the few case reports. In order to elucidate the natural history and treatment outcome, this study investigated advanced HCC patients with an IVC invasion or atrial tumor thrombus. METHODS: Between November 1987 and June 2004, a total of 41 patients were diagnosed as having HCC with IVC or right atrial involvement using the new imaging techniques including a two-dimensional echocardiography. Those patients were stratified into the untreated 'control group' (n=17) and 'treated group' (n=24). The clinical features, treatment outcome and prognosis including patient survival were analyzed. RESULTS: The mean age of the total patients was 55 years (male:female, 33:8). The most common cause of HCC was a hepatitis B virus infection (85.4%), followed by a hepatitis C virus infection (7.4%). According to the Child-Pugh classification, 24 patients were Child-Pugh class A (58.5%), 15 were Child-Pugh class B (36.6%), and 2 were Child-Pugh class C (4.9%). Lung metastases were identified in 10 patients (24.5%). The treatment modalities of the treated group included 11 systemic chemotherapy regimens (5-FU and cisplatin), 10 transarterial chemotherapy regimens, 2 chemoradiation procedures and 1 hepatic resection. The overall survival was 3.0 months (range, 1-29 months). The 6 month survival rate was 23.5% (4/17) in the control group and 29.2% (7/24) in the treated group. The 12 months survival rate was 0% (0/17) and 25.0% (6/24), respectively. Independent prognostic factor affecting the survival was whether or not any treatment had been carried out. CONCLUSIONS: Although the prognosis of advanced HCC with IVC invasion or a right atrial tumor thrombi is poor, treatment might improve the survival rate.

Noninvasive models to predict liver cirrhosis in patients with chronic hepatitis B.

OBJECTIVES: Few noninvasive models of chronic hepatitis B (CHB) to predict liver cirrhosis have been studied. The aim of the current study is to investigate the diagnostic accuracy of two simple novel models of spleen-platelet ratio index (SPRI) and age-spleen-platelet ratio index (ASPRI) in patients with CHB. PATIENTS AND METHODS: A total of 346 consecutive treatment-naïve patients with CHB were retrospectively studied. The aspartate to alanine aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), SPRI, and ASPRI were compared with liver histology. RESULTS: AAR, APRI, SPRI, API, and ASPRI correlated significantly to fibrosis stage (all P<0.001). The diagnostic accuracy of ASPRI was the highest among five tests for prediction of cirrhosis (area under receiver operating characteristic curve, AUROC=0.893). Using a cutoff score of ASPRI>12, the presence of cirrhosis could be correctly identified with a high accuracy (96.3% positive predictive value) in 35 (10.1%) of 346 patients. Similarly, using a cutoff of <5, the presence of cirrhosis could be totally excluded with 100% of negative predictive value in 120 (34.7%) of 346 patients. CONCLUSION: ASPRI was accurate in predicting cirrhosis and screening with ASPRI has the potential to reduce the number of liver biopsies in CHB patients.

Repetitive short-course hepatic arterial infusion chemotherapy with high-dose 5-fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has often been selected as a therapeutic option for patients with advanced hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the efficacy and safety of repetitive HAIC with high-dose 5-fluorouracil (5-FU) and cisplatin given for 3 days in patients with advanced HCC. METHODS: Between January 2001 and December 2004, a total of 41 patients with unresectable advanced HCC were enrolled. The patients underwent HAIC via the implantable port system with 5-FU (at a dose of 500 mg/m(2) on Days 1-3) and cisplatin (at a dose of 60 mg/m(2) on Day 2) every 4 weeks. Tumor response was assessed at the end of every 3 cycles. RESULTS: The median age of the patients was 53 years and 34 patients (82.9%) had evidence of portal vein thrombosis. In total, 230 cycles of HAIC were administered to the 41 patients, with a median of 6 cycles given (range, 1-14 cycles). Nine patients (22.0%) achieved a partial response and 14 patients (34.1%) had stable disease. The median time to disease progression and overall survival were 7.0 months and 12.0 months, respectively. The overall survival was found to be significantly longer in the successful disease control group (patients with a complete response, partial response, and stable disease) than in the disease progression group (median of 14.0 months vs 6.0 months; P < .001). Adverse reactions were tolerable and successfully managed with conservative treatment. CONCLUSIONS: HAIC with high-dose 5-FU and cisplatin given for 3 days achieved effective and safe results in patients with advanced HCC. Therefore, repetitive short-course HAIC with high-dose 5-FU and cisplatin may be useful as an alternative therapeutic option for patients with advanced HCC.

Changes in serum and ascitic monocyte chemotactic protein-1 (MCP-1) and IL-10 levels in cirrhotic patients with spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis (SBP) is a prototypical infectious disease of cirrhotic patients. It has been suggested that cirrhotic patients' response to infection is less effective because of differences in the inflammatory and immune reactions. This study aimed to investigate the expression of the inflammatory cytokines monocyte chemotactic protein-1 (MCP-1) and interleukin-10 (IL-10) in cirrhotic patients with SBP. The MCP1 and IL-10 levels in the sera and ascitic fluids of cirrhotic patients with (n = 40) or without SBP (n=17) were serially analyzed by ELISA. In the non-SBP group, the mean MCP-1 levels in sera and ascites were 53.0 +/- 45.8 pg/mL and 197.5 +/- 109.5 pg/mL, respectively, and the IL-10 levels were 10.9 +/- 9.5 pg/mL and 77.6 +/- 79.7 pg/mL, respectively. In the SBP group, the mean MCP-1 levels in serum and ascites before treatment were 164.7 +/- 126.4 pg/mL and 365.3 +/- 583.0 pg/mL, respectively, and the IL-10 levels were 31.4 +/- 44.1 pg/mL and 188.1 +/- 189.5 pg/mL, respectively. The sera MCP-1 and ascites IL-10 levels differed significantly between the two groups. In the SBP group, sera and ascitic MCP-1 and IL-10 levels fell during treatment. The low MCP-1 and IL-10 levels on the seventh day of treatment were found to have a statistically significant relationship to patient survival. MCP-1 and IL-10 levels in sera and ascites may be related to the clinical course of SBP.

Long-term outcome of chronic hepatitis B based on histological grade and stage.

BACKGROUND AND AIM: This study evaluated the long-term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage. METHODS: A total of 188 patients with chronic hepatitis B were followed for a mean 119.8 months. Ultrasonography and clinical assessment were performed regularly. In addition, liver biopsy specimens were re-evaluated based on histological grade and stage. RESULTS: During follow-up, cirrhosis developed in 62 patients, decompensation in 20 patients, and hepatocellular carcinoma (HCC) in 21 patients. The serum alanine aminotransferase (ALT) level at the time of liver biopsy was significantly correlated with the grades of lobular and porto-periportal activity. The development of cirrhosis correlated well with the grade of porto-periportal activity and stage of fibrosis. The probabilities of developing cirrhosis, decompensation and HCC were significantly higher in patients whose ALT levels were persistently elevated without flares or flared-up without normalization than in patients whose ALT levels flared-up then normalized or were normally sustained. By multivariate analysis, age and biochemical profile during follow-up were independent prognostic factors for chronic hepatitis B. CONCLUSIONS: The results demonstrate that histological grade and stage, and biochemical profile during follow-up in patients with chronic hepatitis B are important prognostic factors. Therefore, effective control of hepatitis activity might improve the long-term outcome of chronic hepatitis B patients.

Efficacy and long-term follow up of combination therapy with interferon alpha and ribavirin for chronic hepatitis C in Korea.

Combination therapy with interferon alpha (IFN-alpha) and ribavirin for 24 or 48 weeks according to HCV genotype has improved the overall sustained virological response (SVR) rates to approximately 40%. The aim of this study was to investigate the long-term efficacy of combination therapy with IFN-alpha and ribavirin for chronic hepatitis C in Koreans. One hundred thirty-eight patients with chronic hepatitis C who received this combination therapy between 1995 and 2003 were analyzed retrospectively. All patients were treated with IFN-alpha 3-6 million units three times weekly in combination with 900-1200 mg/day of ribavirin for 24 weeks. The overall SVR rate was 41.3%. Patients were followed up for a median of 41 months (range, 12-105 months) after completion of therapy. In all of the SVR patients (57 patients), SVR was conserved during the follow-up period. None of the patients progressed to decompensated liver disease or hepatocellular carcinoma (HCC). However, 5 of the 81 non-SVR patients (6.2%) progressed to decompensated liver disease or HCC. In conclusion, combination therapy with IFN-alpha and ribavirin shows good long-term efficacy in patients with chronic hepatitis C in Korea, one of the highest endemic areas of hepatitis B virus (HBV) infection.

Association of genetic variations in CCR5 and its ligand, RANTES with clearance of hepatitis B virus in Korea.

Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. The aim of current study was to investigate the association of clearance of hepatitis B virus (HBV) with promoter polymorphisms within the CC chemokine receptor 5 (CCR5) and its major ligand, regulated upon activation, normal T cells expressed and secreted (RANTES) genes. Five chemokine system polymorphisms (CCR5 Delta32, CCR5 promoter 59029G/A, 59353C/T, RANTES -403G/A, and -28C/G) were studied in a total of 698 subjects. The carriage of each genetic variant was compared among "spontaneously recovered" group (n = 243), "chronic carrier" group (n = 349), and "unexposed" group (n = 106). CCR5 59029G promoter variant was associated with clearance of HBV infection in an acute phase (OR = 1.71, P = 0.006, dominant model; OR = 2.17, P < 0.001, recessive model) and amelioration of hepatic inflammation (P = 0.003) with the control of HBV replication (P = 0.04) in chronic carriers. Interestingly, CCR5 59029 was linked completely to CCR5 59353, and CCR5 Delta32 homozygosity or heterozygosity was not found in any Korean patient. No association was seen with RANTES polymorphisms at position -403 and -28. The CCR5 59029G/CCR5 59353T polymorphism may play a role in the clearance of HBV infection.

The clinical impact of early detection of the YMDD mutant on the outcomes of long-term lamivudine therapy in patients with chronic hepatitis B.

The early emergence of lamivudine (3TC)-resistant tyrosine-methionine-aspartate-aspartate (YMDD) mutants has been reported during 3TC therapy in patients with chronic hepatitis B (CHB) in hepatitis B virus (HBV)-endemic areas; however, its clinical impact during long-term 3TC therapy is unknown. This study was performed to investigate the impact of the early emergence of YMDD mutants 3 months after the initiation of treatment on the outcomes of long-term 3TC therapy in HBV e antigen (HBeAg)-positive CHB. We analysed YMDD genotypes in consecutive samples from 30 patients with HBeAg positive CHB throughout 3TC treatment using both restriction fragment length polymorphism and mass spectrometric assays. Long-term outcome was compared between patients who had YMDD mutations detected at 3 months and those who had no mutations. YMDD mutation was detected in 16 (53.3%) out of 30 patients at 3 months and only the rtM2041 mutation was found. Cumulative HBeAg loss rates at 3 years was 12.5% and 57.4% in patients who had the rtM2041 mutant and wild-type virus at 3 months, respectively (P=0.010). Cumulative viral breakthrough rates at 3 years was 75.0% and 14.3% in patients who had the rtM204I mutant and wild-type virus at 3 months, respectively (P=0.002). Logistic regression revealed that YMDD mutation at 3 months was significantly related to viral breakthrough within 24 months (P=0.003). In conclusion, early detection for HBV YMDD mutation at 3 months may be useful to predict the long-term outcomes of 3TC therapy in patients with HBeAg-positive CHB in HBV-endemic areas.

[Natural history of HBeAg negative chronic hepatitis B virus infection: a cohort study].

BACKGROUND/AIMS: The long-term virologic and biochemical changes in patients with HBeAg negative HBV infection, especially in Asia, remain unclear. To address this issue, we conducted a 3 year- retrospective, cohort study. METHODS: A total of 157 patients with HBeAg negative HBV infection who were monitored without treatment were reviewed between January 1999 and March 2004. Those patients were followed up every 3 months with liver function tests and serologic tests. All patients were stratified into 3 groups; inactive carrier (IC), viremic carrier (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization assay (sensitivity: 1.4 x 10(5)) genomes/mL, Digene Diagnostics, Silver Spring, USA). RESULTS: The median age of enrolled patients was 42.7 years (M:F=2.3:1). By single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over time (P=0.002) and transition rates among three groups after 3 years of follow-up are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a disease state in the middle of transition from IC to CH. CONCLUSIONS: We demonstrated the dynamic changing patterns of HBeAg negative CH with time, of which the change from IC or VC to CH was dominant.

Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid.

Gram-positive bacterial products such as peptidoglycan (PGN) and lipoteichoic acid (LTA) are potent stimulators of innate inflammatory responses. We previously reported that lipopolysaccharide (LPS), a major biologically active agent of gram-negative bacteria, induces a proinflammatory response via the Toll-like receptor (TLR) 4 in hepatic stellate cells (HSCs). Here we investigated the mechanism of proinflammatory action by PGN and LTA in activated human HSCs. Following treatment with either TNF-alpha or IL-1beta, expression of TLR2 and CD14 was determined by real-time PCR and Western blotting. NF-kappaB activation was assessed by NF-kappaB-driven luciferase assay and electrophoretic mobility shift assay. Interleukin-8 (IL-8) from culture supernatant was measured by ELISA. Activated human HSCs express TLR2 and CD14, which are receptors for PGN and LTA signaling. TNF-alpha and IL-1beta significantly upregulated the expression of TLR2 mRNA and protein in HSCs. PGN and LTA induced NF-kappaB activation and stimulated production of IL-8 in HSCs. Pretreatment with TNF-alpha or IL-1beta augmented NF-kappaB activation and IL-8 production in response to PGN or LTA. Both PGN- and LTA-induced NF-kappaB activation and IL-8 secretion were completely inhibited by anti-TLR2 blocking antibody (T2.5). These findings suggest that TNF-alpha or IL-1beta primed HSCs enhance the production of IL-8 in response to PGN and LTA through augmentation of the TLR2 system.

Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma.

PURPOSE: The purpose of this study was to evaluate the long-term tumor response after phase IIb clinical study and the safety of percutaneous holmium-166 ((166)Ho)/chitosan complex injection (PHI) therapy for small hepatocellular carcinoma as a local ablative treatment. (166)Ho is a radioactive isotope derived from natural holmium-165. We developed a (166)Ho/chitosan complex (Milican, Dong Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the radioactive material within the tumor. EXPERIMENTAL DESIGN: Forty patients with single hepatocellular carcinoma < 3 cm in maximal diameter were enrolled in this study. The patients either had refused surgery or were poor surgical candidates and were treated with only single session of PHI. RESULTS: Two months after PHI, complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with hepatocellular carcinoma lesions < 3 cm and in 11 of 12 patients (91.7%) with hepatocellular carcinoma < 2 cm. Tumors recurred in 28 patients during the long-term follow-up period, of which 24 recurred at another intrahepatic site. The 1-year and 2-year cumulative local recurrence rates were 18.5% and 34.9%, respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and 65.3%, respectively. Transient bone marrow depression was serious adverse event requiring hospitalization in two patients. CONCLUSIONS: PHI was found to be a safe and novel local ablative procedure for the treatment of small hepatocellular carcinoma and could be used as a bridge to transplantation. A phase III randomized active control trial is clearly warranted among a larger study population.

Usefulness of urine strip test in the rapid diagnosis of spontaneous bacterial peritonitis.

PURPOSE: Rapid and accurate diagnosis of spontaneous bacterial peritonitis (SBP) is mandatory for timely treatment in cirrhotic patients. The purpose of this study was to assess the usefulness of two different reagent strips, the UriSCAN and the Multistix10SG, for the rapid bedside diagnosis of SBP. METHODS: A total of 75 paracenteses in 53 cirrhotic patients with ascites were performed. All ascitic fluid was analyzed with the two reagent strips, and compared with the manual cell count with differential and ascitic fluid culture. SBP was defined as an ascitic polymorphonuclear cell count > or =250/mm3. RESULTS: SBP was diagnosed in 18 of the 75 samples. If we considered the positive UriSCAN result of 2 or more, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. When we considered the positive UriSCAN result of 3, the sensitivity, specificity, PPV, and NPV were 67%, 100%, 100%, and 89%, respectively. When we considered the positive Multistix10SG result of 3, the sensitivity, specificity, PPV, and NPV were 50%, 100%, 100%, and 87%, respectively. CONCLUSION: Urine reagent strip might be useful for rapid and accurate diagnosis of SBP in cirrhotic patients with ascites.