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Transient elastography (TE) is useful for predicting the fibrosis stage, but it is unsatisfactory as a substitute for liver biopsy, especially in patients with chronic hepatitis B (CHB). This study was performed to establish a reliable model for predicting significant fibrosis (SF) in patients with CHB. All CHB patients who were admitted to undergo liver biopsy were enrolled. They were randomly classified into either a training set ( n = 139) or a validation set ( n = 69). A model for predicting SF was established in the training set and validated in the validation set. Low and high cutoff values (COVs) were chosen for sensitivity ≥ 99% and specificity ≥ 99%, respectively. A total of 208 patients were enrolled. Age was 39 ± 12 years and 149 (71.6%) were men. In the training set, liver stiffness values and serum haptoglobin, apolipoprotein A1, and α2-macroglobulin levels were independent predictors of SF on multivariate analysis. These variables were used to construct a novel model, called the HALF index. The area under the receiver operating characteristics curve of the HALF index for predicting SF was significantly higher than that of TE alone (0.915 vs 0.877, P = 0.010). Using low and high COVs of the HALF index, it appears that approximately half (47.1%) of patients could avoid liver biopsy, with an associated accuracy of 99.0%. A combination of liver stiffness and serum markers identified SF with a high degree of accuracy. Approximately half of all patients with CHB could avoid liver biopsy through the utilization of the HALF index. [ABSTRACT FROM AUTHOR]

We investigated the accuracy of liver stiffness measurement (LSM) in chronic hepatitis C (CHC) in a multicenter, prospective study in South Korea. Between June 2005 and July 2009, 91 CHC patients without a previous history of antiviral treatment, clinical evidences of cirrhosis, coinfection with other viruses, and heavy alcohol consumption and with alanine aminotransferase (ALT) ≤ 5x upper limit of normal, total bilirubin ≤ 1.5 mg/dL, sufficient liver biopsy quality (≥ 15 mm and more than six portal tracts), interquartile range to median liver stiffness (LS) value ratio ≤ 0.21, and more than 10 valid measurements, were recruited. The Batts and Ludwig scoring system was used for histologic assessment. Age-platelet index (API), aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and age-spleen-platelet ratio index (ASPRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of LSM and other noninvasive models. The mean age was 47.9 years, and the mean LS value was 7.7 kPa (44 men and 47 women). LS value was highly correlated to the fibrosis stages ( r = 0.835, P < 0.001). The AUROCs of LSM were 0.909 for ≥ F2, 0.993 for ≥ F3, and 0.970 for F = 4 and were superior to those of API (0.72, 0.858, and 0.948, respectively), APRI (0.780, 0.887, and 0.904, respectively), and ASPRI (0.713, 0.862, and 0.957, respectively). The optimal cutoff LS values were 6.2 kPa for ≥ F2, 7.7 kPa for ≥ F3, and 11.0 kPa for F = 4. Our data suggest that LSM can accurately assess liver fibrosis in patients with CHC and be applied in South Korea. [ABSTRACT FROM AUTHOR]

Background and Aims: The cytokine interleukin (IL)-27 is composed of two subunits, Epstein–Barr virus-induced gene 3 (EBI3) and p28, and IL-27 is a novel IL-12 family member that mediates between the innate and adaptive immune systems. We previously identified four polymorphisms in the human IL-27 gene and we suggested that the polymorphism of IL-27 is associated with the susceptibility to asthma. IL-27 transcripts are significantly elevated in active Crohn's disease (CD) but not in ulcerative colitis (UC). To determine whether these IL-27 single nucleotide polymorphisms are associated with the susceptibility to inflammatory bowel disease (IBD), the genotype and allelic frequencies of the IL-27 polymorphisms were analyzed between the IBD patients and the healthy controls. Methods: Genotype analysis of the IL-27 gene was performed by the single-base extension (SBE) method. The haplotype frequencies of IL-27 for multiple loci were estimated using the expectation maximization (EM) algorithm. Results: The genotype frequencies of the g.-964A > G polymorphism in the IBD patients were significantly different from those of the healthy control group ( P = 0.001). In both the UC and CD patients, the genotype frequencies of the g.-964A > G polymorphism were also significantly different from the frequencies of the healthy control group ( P = 0.009). The frequencies of the AGT and GGT haplotypes were significantly different between the healthy control group and the IBD patient group ( P = 0.00004 and 0.021, respectively). Conclusion: Our results suggest that the g.-964A > G polymorphism of the IL-27 gene located on the IBD1 locus might be associated with the susceptibility to IBD. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine (LAM)- resistant patients. Methods: We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using the restriction fragment mass polymorphism (RFMP) method. Results: Reversion to pure YMDD wild-type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. Adefovir-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild-type HBV (−3.1 log10 copies/mL vs−3.4 log10 copies/mL, P > 0.05). Conclusions: ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM-resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance. [ABSTRACT FROM AUTHOR]

Background/Aims: Psychological factors and subtle histopathological changes have been implicated in irritable bowel syndrome (IBS). The aims of the present study were to investigate whether the numbers of enterochromaffin (EC) cells, mast cells, and lamina propria T lymphocytes are altered in IBS, and evaluate the relationship of such alterations with psychological factors. Methods: Forty-two consecutive IBS patients (M : F = 17:25, mean age 48 years) fulfilling the Rome III criteria and twelve asymptomatic healthy controls underwent rectal biopsy. Immunostaining was performed for EC cells, mast cells, and lamina propria T lymphocytes. Results: The IBS group included five post-infectious (PI) IBS and 37 non-PI IBS patients. Significantly more EC cells, mast cells and lamina propria T lymphocytes were observed in PI IBS patients. Mast cells significantly increased in non-PI IBS-D (diarrhea) patients, but not in non-PI IBS-C (constipation) and non-PI IBS-M (mixed) patients. Enterochromaffin cell numbers were not significantly altered in non-PI IBS patients. Anxiety and depression scores did not differ between IBS patients with and without abnormal increase in EC cell or mast cell counts, defined as more than the mean of controls + 2 standard deviations. Enterochromaffin cell, mast cell, or lamina propria T lymphocyte numbers were poorly correlated with anxiety and depression scores in the IBS group. Conclusions: Enterochromaffin cells, mast cells, and lamina propria T lymphocytes significantly increase in PI IBS, whereas only mast cells significantly increase in non-PI IBS-D. Such histopathological changes do not seem to be directly associated with psychological factors. [ABSTRACT FROM AUTHOR]

Background and Aims: There has been no reliable and valid instrument to measure health-related quality of life for Asian patients with chronic liver disease. The aim of the present study was to develop and evaluate a chronic liver disease-specific quality of life (CLD-QOL) questionnaire for Korean patients with chronic liver disease. Methods: Content-validated items were evaluated psychometrically in 271 patients with chronic liver disease recruited from seven university hospitals in Korea. The participants were asked to complete a preliminary questionnaire comprising the content-validated items and the Short Form-36 Health Survey. The Child–Pugh classification was used to classify the severity of liver cirrhosis. Results: Factor analysis extracted a five-factor solution from 27 preliminary items, which were generated by an expert panel and a pilot study, but factor and a multidimensional scaling analysis revealed that four items were not loaded significantly on any factor, suggesting that the four items might be heterogeneous. After deletion of these four items, a multiscaling analysis strongly supported item convergence and discriminant validity. The CLD-QOL was associated significantly with the Child–Pugh classification and the type of patient status (inpatient/outpatient) and was moderately correlated with the subscales of the Short Form-36 Health Survey. The values of Cronbach's alpha for the subscales of the novel CLD-QOL questionnaire were all greater than 0.70. Conclusions: The novel CLD-QOL questionnaire we developed is an easily applicable tool that exhibits excellent psychometric properties for Korean patients with chronic liver disease. It is recommended for the CLD-QOL to apply for Asian patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

Background: The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)-α and interleukin(IL)-10 gene promoter. Methods: A total of 412 Korean patients with HBV infection (72 inactive carriers, 261 witih chronic hepatitis, 79 with liver cirrhosis) and 204 healthy individuals who recovered from HBV infection, were studied. The polymorphisms in IL-10 gene promoter (−1082, −819, −592), and TNF-α gene promoter (−308, −238) were assessed by single base primer extension assay. Results: The frequency of C/C genotype at position −592 of IL-10 gene promoter was higher in the HBV clearance group than that in the persistence group in univariate analysis (12.7% vs 7.5%, P = 0.036). The IL-10 gene promoter −592 C/C genotype was related to clearance of HBV infection in logistic regression analysis after adjusting for age and sex ( P = 0.003). Genotype frequencies of TNF-α gene promoter at position −308 and −238 were not different between the clearance and the persistence group in univariate analysis, but in multivariate analysis after adjusting for age and sex, −308G/−238G homozygotes were associated with HBV persistence ( P = 0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease. Conclusions: The carriers of the −592A allele in the IL-10 promoter and −308G/−238G haplotype homozygotes in the TNF-α promoter region have higher risk of persistent HBV infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Duodenal acidification might increase sensitivity to gastric distension, which seems to play a role in the genesis of dyspeptic symptoms in a subset of patients with functional dyspepsia. The aim of the present study was to investigate the characteristics of dyspeptic symptoms associated with hypersensitivity to gastric distension induced by duodenal acidification. Methods: An infusion tube and a barostat bag were positioned in the duodenum and gastric fundus, respectively. Sensitivity to stepwise fundic distensions with severity scoring of the seven dyspeptic symptoms was assessed before and during duodenal acid infusion in 20 healthy subjects. Results: Acid infusion significantly decreased the pressures and the corresponding wall tensions at the thresholds for discomfort. At the distending level of minimal distending pressure (MDP) + 2 mmHg, significantly higher scores of fullness and bloating were obtained during acid infusion. With distending stimuli of MDP + 4 and 6 mmHg, fullness, bloating, nausea, satiety, epigastric burning and epigastric pain were significantly more severe during acid infusion than before acid infusion. At the level of MDP + 8 mmHg, the severity of epigastric pain was significantly greater, compared with that before acid infusion. Conclusions: Duodenal acidification might aggravate dyspeptic symptoms through the induction of hypersensitivity to gastric distension in healthy individuals. Those symptoms are diverse and variable, depending on the strength of the distending stimuli. [ABSTRACT FROM AUTHOR]