Changes in liver stiffness values assessed using transient elastography in chronic hepatitis B patients treated with tenofovir disoproxil fumarate: a prospective observational study.

BACKGROUND/AIMS: Regression of liver fibrosis during antiviral therapy in chronic hepatitis B (CHB) patients has been demonstrated, but data on the influence of long-term treatment with tenofovir disoproxil fumarate (TDF) on liver stiffness (LS) measured by transient elastography are scarce. We aimed to investigate the changes in LS values during the 144-week TDF therapy in treatment-naïve CHB patients. METHODS: This prospective observational study was conducted from April 2015 to July 2020 at CHA Bundang Medical Center. Laboratory tests and LS measurements were performed at baseline and repeated at weeks 12, 24, 48, 96, and 144. A significant decline in LS was defined as ≥ 30% decrease in LS value at week 96 from baseline. RESULTS: A total of 48 treatment-naïve CHB patients initiating TDF therapy were screened, and 36 patients were included in the final analysis (median age, 46 [interquartile range, 34.5-55.8] years; 19 men [52.8%]). During TDF therapy, the median LS values decreased from 13.8 kPa at baseline to 8.7 kPa, 6.5 kPa, and 6.4 kPa at weeks 48, 96, and 144, respectively (all P < 0.001). At week 96, virological and biochemical responses were achieved in 34 (94.4%) patients and 20 (76.9%) patients, respectively. Moreover, 21 of 36 (58.3%) patients showed a significant decline in LS value. A higher baseline LS value was a single independent predictor for the reduction in LS value at week 96 from baseline (P < 0.001). CONCLUSIONS: During the 144-week TDF therapy, LS values declined significantly in treatment-naïve CHB patients.

Validation of risk prediction scores for hepatocellular carcinoma in patients with chronic hepatitis B treated with entecavir or tenofovir.

Several prediction scores for the early detection of hepatocellular carcinoma (HCC) are available. We validated the predictive accuracy of age, albumin, sex, liver cirrhosis (AASL), RESCUE-B, PAGE-B and modified PAGE-B (mPAGE-B) scores in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF). Between 2007 and 2014, 3171 patients were recruited (1645, ETV; 1517, TDF). The predictive accuracy of each prediction score was assessed. The mean age of the study population (1977 men; 1194 women) was 48.8 years. Liver cirrhosis was present in 1040 (32.8%) patients. During follow-up (median, 58.2 months), 280 (8.8%) patients developed HCC; these patients were significantly older; more likely to be male; had significantly higher proportions of liver cirrhosis, hypertension and diabetes; and had significantly higher values for the four risk scores than those who did not develop HCC (all P < .05). Older age (hazard ratio [HR] = 1.048), male sex (HR = 2.142), liver cirrhosis (HR = 3.144) and prolonged prothrombin time (HR = 2.589) were independently associated with an increased risk of HCC (all P < .05), whereas a higher platelet count (HR = 0.996) was independently associated with a decreased risk of HCC (P < .05). The predictive accuracy of AASL score was the highest for 3- and 5-year HCC predictions (areas under the curve [AUCs] = 0.818 and 0.816, respectively), followed by RESCUE-B, PAGE-B and mPAGE-B scores (AUC = 0.780-0.815 and 0.769-0.814, respectively). In conclusion, four HCC prediction scores were assessed in Korean CHB patients treated with ETV or TDF. The AASL score showed the highest predictive accuracy.

Validation of the CAMD Score in Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy.

BACKGROUND & AIMS: Researchers previously developed a scoring system to determine the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, based on the presence of cirrhosis, patient age, male sex, and diabetes (called the CAMD scoring system). We validated the CAMD scoring system and compared its performance with that of other risk assessment models in an independent cohort. METHODS: We followed up 3277 patients with chronic HBV infection (mean age, 48.7 y; 62.6% male; 32.4% with cirrhosis) who were treated with entecavir (n = 1725) or tenofovir (n = 1552) as the first-line antiviral agent in 4 academic teaching hospitals in the Republic of Korea. The primary outcome was development of HCC. We evaluated the ability of the CAMD, PAGE-B, and mPAGE-B scoring systems to identify patients who would develop HCC using integrated area under the curve (iAUC) analysis. RESULTS: Over a median follow-up period of 58.2 months, 8.9% of the patients developed HCC. Patients who developed HCC were older, more likely to be male, and had higher proportions of cirrhosis and diabetes than patients who did not develop HCC (all P < .05). CAMD scores identified patients who developed HCC with an iAUC of 0.790, mPAGE-B scores with an iAUC of 0.769, and PAGE-B scores with an iAUC of 0.760. The 5-year cumulative risks of HCC were 1.3% in patients with low CAMD scores (<8), 8.0% in patients with intermediate CAMD scores (8-13), and 24.3% in patients with high CAMD scores (>13) (P < .001 for comparison of low- vs intermediate-score groups and between intermediate- vs high-score groups). The predicted and observed probabilities of HCC had excellent agreement. CONCLUSIONS: We validated the CAMD scoring system in determining the risk of HCC in patients with chronic HBV treatment receiving entecavir or tenofovir treatment. Validation was performed in a cohort of patients in the Republic of Korea, where most patients have genotype C2 HBV infection.

A multicenter study of entecavir vs. tenofovir on prognosis of treatment-naïve chronic hepatitis B in South Korea.

BACKGROUND & AIMS: It is currently unclear which antiviral agent, entecavir (ETV) or tenofovir disoproxil fumarate (TDF), is superior for improving prognosis in patients with chronic hepatitis B (CHB). Here, we assessed the ability of these 2 antivirals to prevent liver-disease progression in treatment-naïve patients with CHB. METHODS: From 2012 to 2014, treatment-naïve patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from 4 academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed. RESULTS: In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was not statistically different between the ETV and TDF groups (1.92 vs. 1.69 per 100 person-years [PY], respectively; adjusted hazard ratio [HR] 0.975 [p = 0.852] by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR 1.021 [p = 0.884] and 0.998 [p = 0.988], respectively). The annual incidence of death or OLT was not statistically different between the ETV and TDF groups (0.52 vs. 0.53 per 100 PY, respectively; adjusted HR 1.202 [p = 0.451]). PS-matched and ITPW analyses yielded similar patterns of results (HR 1.248 [p = 0.385] and 1.239 [p = 0.360], respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all p >0.05). CONCLUSIONS: The overall prognosis in terms of HCC and death or OLT was not statistically different between the ETV and TDF groups. Further studies are needed to validate our results. LAY SUMMARY: It is currently unclear which antiviral agent, entecavir or tenofovir disoproxil fumarate, is superior for improving prognosis in patients with chronic hepatitis B virus infection. In this analysis we found that there was no difference in terms of overall prognosis, including risk of hepatocellular carcinoma, death, or the need for a liver transplant, in patients receiving either antiviral.

Validation of PAGE-B model in Asian chronic hepatitis B patients receiving entecavir or tenofovir.

BACKGROUND & AIMS: A new hepatocellular carcinoma risk prediction model, PAGE-B, which includes age, gender and platelet count as constituent variables, has recently been proposed in Caucasian chronic hepatitis B patients. We validated PAGE-B model and compared its accuracy with that of conventional risk prediction models in Asian chronic hepatitis B patients. METHODS: Chronic hepatitis B patients treated with entecavir or tenofovir were consecutively recruited. The performance of PAGE-B and three conventional risk prediction models (CU-HCC, GAG-HCC and REACH-B) were analysed. RESULTS: A total of 1092 chronic hepatitis B patients (668 men, 61.2%) were selected between August 2006 and January 2015. The mean age was 48 years. During the follow-up period (median, 43.6 months), 36 (3.3%) patients developed hepatocellular carcinoma. Older age (hazard ratio [HR]=1.077), male gender (HR=3.676) and lower platelet count (HR=0.984) were independent predictors of hepatocellular carcinoma development. The PAGE-B showed similar area under receiver operating characteristic curves (AUROCs) to GAG-HCC and CU-HCC at 3 years (0.777 vs 0.793 and 0.743, respectively; all P>.05) and 5 years (0.799 vs 0.803 and 0.744, respectively; all P>.05), whereas the AUROCs of PAGE-B were significantly higher than those of the REACH-B (0.602 at 3 years and 0.572 at 5 years, P<.05). CONCLUSIONS: Our study demonstrated that PAGE-B is applicable to Asian chronic hepatitis B patients receiving ETV or TDF therapy. The PAGE-B showed similar predictive performance to GAG-HCC and CU-HCC.

Multicenter comparison of PEG-IFN α2a or α2b plus ribavirin for treatment-naïve HCV patient in Korean population.

BACKGROUND: Two recent Italian studies suggested that Pegylated-interferon (PEG-IFN) alfa-2a achieves a higher sustained virological response (SVR) rate than PEG-IFN alfa-2b. We intended to compare the efficacy and safety of PEG-IFN alfa-2a with those of PEG-IFN alfa-2b in Korean patients with chronic hepatitis C virus (HCV). METHODS: This retrospective, multi-center trial was conducted on 661 treatment-naïve chronic HCV patients. Patients received PEG-IFN alfa-2a (180 µg/week; n=402) or PEG-IFN alfa-2b (1.5 µg/kg/week; n=259) with ribavirin (800-1200 mg/day) for 24 or 48 weeks according to HCV genotypes. RESULTS: Early virologic response and sustained virologic response (SVR) rates were not significantly different between two PEG-IFN groups both in patients with HCV genotype 1 (all P-values>0.05) and 2/3 (all P-values>0.05). SVR rates were not different between two groups in each categorized baseline characteristics: age (years) (≤ 50 and >50), HCV viral load (IU/mL) (≤ 7 × 10(5) and >7 × 10(5)), and hepatic fibrosis (F0-2 and F3-4) (all P-values >0.05). In additional analysis for 480 patients who sufficiently complied with treatment doses and duration (80/80/80 rule) and propensity-score matched analysis, SVR rates were not different between two groups both in patients with HCV genotype 1 and 2/3 (all P-values >0.05). Adverse event rates were similar between two groups. CONCLUSIONS: Unlike the Western data, efficacy and safety of PEG-IFN alfa-2a were similar to those of PEG-IFN alfa-2b in chronically HCV-infected Korean patients regardless of age, HCV viral load, and hepatic fibrosis.

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir.

UNLABELLED: Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (-0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(-) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients. CONCLUSION: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated.

Hepatitis A virus genotype and its correlation with the clinical outcome of acute hepatitis A in Korea: 2006-2008.

Korea has recently experienced a nationwide outbreak of hepatitis A. This study aimed to investigate hepatitis A virus (HAV) genotypes and to compare clinical features between patients infected with HAV genotype IA and those with genotype IIIA. From September 2006 to August 2008, 595 patients with symptomatic hepatitis A were enrolled prospectively in four hospitals in Korea. Among them, 556 patients participated in this study by providing serum or stool samples for genotypic analysis. HAV RNA was detected in 499 patients (89.7%). Major genotypes included IA (n = 244, 48.9%) and IIIA (n = 244, 48.9%), and the remaining genotype was IB (n = 11, 2.2%). From September 2006 to August 2007, the distribution of genotypes IA and IIIA were 64.6% and 35.6%, respectively, which changed to 42.3% and 54.6%, respectively, from September 2007 to August 2008, indicating change of circulating HAV genotypes in the study period from IA to IIIA. Major patterns of amino acid substitution in the VP3/VP1 junction region were observed at position 512 (P → L) in genotype IA and at 520 (R → K) in genotype IIIA. Patients with genotype IIIA infection showed significantly higher aminotransferase levels, prothrombin time, and leukocyte count, with more severe symptoms than those with genotype IA at the time of admission. These results suggest the occurrence of a change of circulating HAV genotypes in recent community-wide outbreaks of hepatitis A in Korea, and genotype IIIA infection, compared with genotype IA infection, might show more severe clinical manifestations.

Atypical manifestations of hepatitis A infection: a prospective, multicenter study in Korea.

The clinical outcome of symptomatic hepatitis A and the incidence and clinical characteristics of atypical presentation of hepatitis A were studied using prospective, multicenter design. The atypical presentation included delayed anti-hepatitis A virus (HAV) immunoglobulin M (IgM) seroconversion defined as positive anti-HAV IgM on the repeated test within 7 days of hospital admission after the initially negative result, prolonged cholestasis, and acute kidney injury (AKI). A total of 595 patients with symptomatic hepatitis A requiring hospital admission were enrolled prospectively from September 2006 to August 2008 in four major hospitals in a Korean city with a population of approximately 1 million. Clinical outcomes of symptomatic hepatitis A showed a case fatality rate of 0.2%, and fulminant hepatitis in 0.5%. Delayed anti-HAV IgM seroconversion was found in 6.4%, and was significantly associated with shorter intervals from symptom onset to hospital admission, higher body mass index, and lower alanine aminotransferase (ALT) level at admission. Prolonged cholestasis was found in 4.7% of patients, and could be predicted by preexisting chronic hepatitis B viral infection, prolonged prothrombin time, and higher total bilirubin level. AKI was complicated in 1.5%, which could be predicted by lower albumin level, higher ALT level, and higher white blood cell (WBC) count. More than half of the patients required hemodialysis. Substantial occurrence of delayed anti-HAV IgM seroconversion, prolonged cholestasis, and AKI was confirmed with various predictable factors, which could be helpful for accurate diagnosis and management of hepatitis A patients.

Decrease in waist-to-hip ratio reduced the development of chronic kidney disease in non-obese non-alcoholic fatty liver disease.

To date, there are few studies that have evaluated the prognostic impact of changes in abdominal obesity or weight on long-term adverse kidney outcomes in non-alcoholic fatty liver disease (NAFLD). We investigated the effect of changes in waist-to-hip ratio (WHR) and body weight (BW) on chronic kidney disease (CKD) development, especially in non-obese NAFLD patients. We included 6,137 participants from a community-based prospective cohort with 12-year follow-up in Korea. NAFLD patients were categorized according to time-averaged percent changes in WHR and BW (≤-5%, >-5% to <5%, and ≥5%). Compared to non-obese controls, non-obese NAFLD was significantly associated with an increased risk of incident CKD (hazard ratio [HR] = 1.238, 95% confidence interval [CI] = 1.006-1.524). In 1,563 NAFLD patients, compared to patients with minimal changes in WHR (>-5% to <5%), patients with a decreased WHR (≤-5%) had a significantly attenuated risk of CKD development (HR = 0.300; 95% CI = 0.194-0.464). Furthermore, risk reduction from decreased WHR for developing CKD remained significant in non-obese NAFLD patients (HR = 0.290; 95% CI = 0.114-0.736). In conclusion, a decrease in WHR of more than 5% significantly reduced the risk of CKD development in NAFLD patients, even in those who were non-obese. Thus, serial monitoring of WHR may be prioritized in the management of NAFLD.

STAT3 expression in gastric cancer indicates a poor prognosis.

BACKGROUND AND AIM: Signal transducers and activators of transcription (STAT) behave as signal transducers in the cytoplasm and as transcription factors in the nucleus. In the current study, we analyzed the immunohistochemical staining patterns of gastrectomy tissue specimens. We investigated the expression of STAT3 and STAT5 and estimated the relationship between STAT and cancer prognosis. METHODS: One hundred patients who underwent gastrectomy due to gastric adenocarcinoma at Bundang CHA hospital between January 2000 and May 2005 were studied. Immunohistochemistry was carried out using antibodies against STAT3 and STAT5. The interpretation of the immunohistochemical staining was based on the proportion of stained cells in the field: positive, > 10% stained cells; and negative, < 10% stained cells. RESULTS: The longest diameter of tumor was 4.67 cm in the positive group and 3.76 cm in the negative group, and these results were not statistically different (P-value = 0.112). Higher T (primary tumor) value (P-value = 0.05), more regional lymph node invasion (P-value = 0.008) and higher TNM staging (P-value = 0.069) were significantly related to STAT3 positivity, but Helicobacter pylori infection or atrophic gastritis were not related. A lower survival rate was observed in the STAT3-positive group (P-value = 0.001). The results of STAT5 were not statistically different with respect to TNM staging and survival (P-value = 0.958). We thus report that the immunohistochemical results of STAT3 revealed a significant association with TNM staging and survival. CONCLUSION: We anticipate that STAT3 may be used as a molecular staging biomarker predicting poor prognosis of gastric cancer.

Bowel obstruction caused by an intramural duodenal hematoma: a case report of endoscopic incision and drainage.

Complications associated with an intramural hematoma of the bowel, is a relatively unusual condition. Most intramural hematomas resolve spontaneously with conservative treatment and the patient prognosis is good. However, if the symptoms are not resolved or the condition persists, surgical intervention may be necessary. Here we describe internal incision and drainage by endoscopy for the treatment of an intramural hematoma of the duodenum. A 63-yr-old woman was admitted to the hospital with hematemesis. The esophagogastroduodenoscopy (EGD) showed active ulcer bleeding at the distal portion of duodenal bulb. A total of 10 mL of 0.2% epinephrine and 2 mL of fibrin glue were injected locally. The patient developed diffuse abdominal pain and projectile vomiting three days after the endoscopic treatment. An abdominal computed tomography revealed a very large hematoma at the lateral duodenal wall, approximately 10 x 5 cm in diameter. Follow-up EGD was performed showing complete luminal obstruction at the second portion of the duodenum caused by an intramural hematoma. The patient's condition was not improved with conservative treatment. Therefore, 21 days after admission, endoscopic treatment of the hematoma was attempted. Puncture and incision were performed with an electrical needle knife. Two days after the procedure, the patient was tolerating a soft diet without complaints of abdominal pain or vomiting. The hematoma resolved completely on the follow-up studies.

Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake. METHODS: Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors. RESULTS: Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9-8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122-8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404-7.228; P=0.47). CONCLUSION: Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

Development of a New Nomogram Including Neutrophil-to-Lymphocyte Ratio to Predict Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

The neutrophil-to-lymphocyte ratio (NLR) has recently been reported to predict the prognosis of hepatocellular carcinoma (HCC). We explored whether NLR predicted the survival of patients with HCC undergoing transarterial chemoembolization (TACE), and developed a predictive model. In total, 1697 patients with HCC undergoing TACE as first-line therapy at two university hospitals were enrolled (derivation set n = 921, internal validation set n = 395, external validation set n = 381). The tumor size, tumor number, AFP level, vascular invasion, Child-Pugh score, objective response after TACE, and NLR, selected as predictors of overall survival (OS) via multivariate Cox's regression model, were incorporated into a 14-point risk prediction model (SNAVCORN score). The time-dependent areas under the receiver-operating characteristic curves for OS at 1, 3, and 5 years predicted by the SNAVCORN score were 0.812, 0.734, and 0.700 in the derivation set. Patients were stratified into three risk groups by SNAVCORN score (low, 0-4; intermediate, 5-9; high, 10-14). Compared with the low-risk group, the intermediate-risk (HR 3.10, p < 0.001) and high-risk (HR 7.37, p < 0.001) groups exhibited significantly greater mortality. The prognostic performance of the SNAVCORN score including NLR in patients with HCC treated with TACE was remarkable, much better than those of the conventional scores. The SNAVCORN score will guide future HCC treatment decisions.

Occult hepatitis B virus infection in pregnant woman and its clinical implication.

BACKGROUND/AIMS: The objective of this study was to document the prevalence rate of occult hepatitis B virus (HBV) in healthy pregnant woman and the possibility of transmission to the foetus. METHODS: This study was performed prospectively with 202 healthy pregnant women. HBV-DNA testing was performed using two specific quantitative tests with two independent sets of sera and cord blood. DNA sequencing analysis was carried out to confirm the specificity of polymerase chain reaction (PCR) product of HBV-DNA testing. RESULTS: Eight of 202 (4%) individuals with the TaqMan PCR assay and 23 of 202 (11.4%) with the COBAS Amplicor HBV Monitor test were HBV-DNA positive. Six (3%) individuals were positive with both methods. Sequencing and genotyping analysis of HBV polymerase gene with sera of the 75th subject resulted in genotype C. HBV-DNA testing with four cord blood samples showed that all were HBV-DNA negative. CONCLUSION: Occult HBV infection shows a difference in prevalence rate depending on the test method but the existence has been confirmed by sequencing analysis. Our results also suggest that vertical transmission through the cord blood is not so high as to be clinical problems and warrants further investigation.

[Clinical characteristics of health screen examinees with nonalcoholic fatty liver and normal liver function test].

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is known to be closely associated with various metabolic abnormalities including metabolic syndrome. However, there are few data available on the association of metabolic syndrome with the sonographically fatty liver and normal range of liver function test. The purposes of this study were to find the incidence of ultrasonographic fatty liver with normal range of liver function test and to evaluate the association with metabolic syndrome in apparently healthy Korean adults. METHODS: We examined 538 men and women, aged 30-80 years, who participated in a health screening test. Among the people with normal ALT level, we compared clinical characteristics and prevalence of metabolic disorders according to the presence of nonalcoholic sonographyally fatty liver, and then they were subdivided into upper normal range and lower normal range of ALT level. RESULTS: Compared to the people without sonographic fatty liver, people with sonographic fatty liver and normal range of ALT level had odds ratios for metabolic syndrome of 4.53, insulin resistance 4.83, hypertension 2.69, dyslipidemia 6.90, and obesity 5.39, respectively. Furthermore, the prevalence of metabolic syndromes and other metabolic disorders were increased in both sonographically fatty liver group or ultrasonographically normal liver group with upper normal range of ALT level compared with lower normal ALT level (p<0.01). CONCLUSIONS: The nonalcoholic sonographically fatty liver was strongly associated with metabolic syndrome and common metabolic abnormalities even with normal liver function test.

[Hepatitis B core antigen expression pattern predicts response to lamivudine therapy in patients with chronic hepatitis B].

BACKGROUNDS/AIMS: Negative hepatitis B core antigen (HBcAg) staining in hepatocytes is indicative of viral replication by an active immune response. HBcAg is expressed mainly in the cytoplasm in patients with active hepatitis and hepatocyte regeneration, and mainly in the nuclei of hepatocytes in patients with minimal liver injury in the absence of hepatocyte regeneration. The aim of this study was to elucidate whether the existence and expression pattern of HBcAg predicts the response to antiviral treatment. METHODS: The study involved 58 patients with biopsy-proven chronic hepatitis B who were treated with lamivudine. Hepatitis B e antigen (HBeAg), antibody to HBeAg, hepatitis B virus DNA, and alanine aminotransferase in serum were recorded every 3 months. The inflammation grade and the fibrosis stage of chronic hepatitis were scored from 0 to 4 according to lobular inflammation, portal inflammation, periportal inflammation, and fibrosis. RESULTS: The 58 patients included 49(84%) HBcAg-positive patients, with HBcAg staining confined to the cytoplasm in 15(31%) and in both cytoplasm and nuclei in 34(69%). The grade of lobular inflammation and the total histology score were significantly higher in patients with cytoplasmic expression of HBcAg than in HBcAg-negative patients (lobular inflammation: 2.9 vs 2.1, P=0.02; total histology score: 12.2 vs 10.3, P=0.04). The virologic responses at 3, 6, 9, and 12 months differed significantly between the cytoplasmic and mixed expression groups (P<0.01). CONCLUSIONS: The expression pattern of HBcAg (including its possible absence) before initial therapy appears to predict the response to antiviral treatment.

Sarcopenia Predicts Prognosis in Patients with Newly Diagnosed Hepatocellular Carcinoma, Independent of Tumor Stage and Liver Function.

PURPOSE: The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a three-dimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatmentweighting (IPTW) method was used to minimize confounding bias. RESULTS: Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ≤ 45.8 cm/m2 for males and ≤ 43.0 cm/m2 for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associatedwith prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival. CONCLUSION: The presence of sarcopenia at HCC diagnosis is independently associated with survival.

Low hair copper concentration is related to a high risk of nonalcoholic fatty liver disease in adults.

Copper, an essential micronutrient, is required for lipid metabolism, mitochondrial function, iron metabolism, and antioxidant defense. Copper deficiency has been linked to alterations in lipid metabolism and various metabolic processes of the liver, including nonalcoholic fatty liver disease (NAFLD); however, most of these studies relied on copper measurements in the blood or tissues. In this study, we investigated the association between hair copper concentration and NAFLD in Korean adults, independent of metabolic syndrome status. Clinical and laboratory parameters, including factors of metabolic syndrome, were analyzed in 751 Korean adults divided into quintiles, according to hair copper concentration. Lower hair copper concentration was significantly correlated with higher body mass index, waist circumference, blood pressure, and lower levels of high-density lipoprotein cholesterol. Subjects with NAFLD showed significantly lower hair copper concentrations, and the risk of NAFLD was significantly higher for the lower hair copper quintile groups even after adjusting for metabolic syndrome-related factors. Overall, this study suggests that lower hair copper concentration could be associated with NAFLD, independent of metabolic syndrome factors.

[Abnormal liver function tests in pregnancy: a single institution experience].

BACKGROUND/AIMS: Elevated transaminase levels are often detected during pregnancy. Causes are variable and difficult to differentiate. Furthermore, there is no practical guideline for abnormal transaminase levels in pregnancy. The aim of this study was to suggest a strategy for managing elevated transaminase level during pregnancy. METHODS: One hundred and fifty-five women with elevated transaminase level were included from an antenatal care center between January 1, 2003 and December 31, 2004. Another 221 women with normal transaminase levels were enrolled as control group. We analyzed documented causes, changes in laboratory tests, and pregnancy outcomes. RESULTS: Two groups showed no difference in baseline characteristics except the duration of pregnancy, parity, and albumin level. Of abnormal results, 39.4% occurred between 30 and 40 gestational weeks while 29% occurred between 10 and 20 gestational weeks. Common causes were hyperemesis gravidarum followed by pre-eclampsia, viral hepatitis, and HELLP syndrome. Excluding viral hepatitis, 69 patients showed abnormal results in the first two trimesters and the results were normalized during the follow-up period. AST and ALT levels were 52.9 (+/-49.6) IU/L and 83.3 (+/-77.0) IU/L during the first two trimesters in the patient group. Abnormal results during the third trimester were associated with shorter duration of pregnancy. CONCLUSIONS: Elevated transaminase levels up to 3 to 4 times of the upper normal limit during the first two trimesters could be safely observed with careful history taking and hepatitis viral antigen tests. However, abnormal results in the third trimester were associated with a shorter duration of pregnancy and should be managed carefully.