rt269L-Type hepatitis B virus (HBV) in genotype C infection leads to improved mitochondrial dynamics via the PERK-eIF2α-ATF4 axis in an HBx protein-dependent manner.

BACKGROUND: In our previous report, the rt269I type versus the rt269L type in genotype C2 infection led to poor clinical outcomes and enhanced mitochondrial stress in infected hepatocytes. Here, we sought to investigate differences between the rt269L and rt269I types in mitochondrial functionality in hepatitis B virus (HBV) genotype C2 infection, mainly focusing on endoplasmic reticulum (ER) stress-mediated autophagy induction as an upstream signal. METHODS: Mitochondrial functionality, ER stress signaling, autophagy induction, and apoptotic cell death between rt269L-type and rt269I-type groups were investigated via in vitro and in vivo experiments. Serum samples were collected from 187 chronic hepatitis patients who visited Konkuk or Seoul National University Hospital. RESULTS: Our data revealed that genotype C rt269L versus rt269I infection led to improved mitochondrial dynamics and enhanced autophagic flux, mainly due to the activation of the PERK-eIF2α-ATF4 axis. Furthermore, we demonstrated that the traits found in genotype C rt269L infection were mainly due to increased stability of the HBx protein after deubiquitination. In addition, clinical data using patient sera from two independent Korean cohorts showed that, compared with rt269I, rt269L in infection led to lower 8-OHdG levels, further supporting its improved mitochondrial quality control. CONCLUSION: Our data showed that, compared with the rt269I type, the rt269L type, which presented exclusively in HBV genotype C infection, leads to improved mitochondrial dynamics or bioenergetics, mainly due to autophagy induction via activation of the PERK-eIF2α-ATF4 axis in an HBx protein-dependent manner. This suggests that HBx stability and cellular quality control in the rt269L type predominating in genotype C endemic areas could at least partly contribute to some distinctive traits of genotype C infection, such as higher infectivity or longer duration of the hepatitis B e antigen (HBeAg) positive stage.

MELD-GRAIL-Na Is a Better Predictor of Mortality Than MELD in Korean Patients with Cirrhosis.

Background and Objectives: The Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) are classical systems for predicting mortality in patients with liver cirrhosis (LC). The MELD-GFR assessment in liver disease-sodium (MELD-GRAIL-Na) was designed to better reflect renal function and, therefore, provide better mortality predictions. This study aimed to compare the prediction accuracy of MELD-GRAIL-Na compared to CP and MELD in predicting short-term (1- and 3-month) mortality in Korean patients. Materials and Methods: Medical records of patients with LC admitted to the Konkuk University Hospital from 2015 to 2020 were retrospectively reviewed. Predictive values of the CP, MELD, and MELD-GRAIL-Na for 1-month and 3-month mortality were calculated using the area under the receiver operating curve (AUROC) and were compared using DeLong's test. Results: In total, 1249 patients were enrolled; 102 died within 1 month, and 146 within 3 months. AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.831, 0.847, and 0.857 for 1-month mortality and 0.837, 0.827, and 0.835 for 3-month mortality, respectively, indicating no statistical significance. For patients with CP classes B and C, AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.782, 0.809, and 0.825 for 1-month mortality and 0.775, 0.769, and 0.786 for 3-month mortality, respectively. There was a significant difference between CP and MELD-GRAIL-Na in predicting 1-month mortality (p = 0.0428) and between MELD and MELD-GRAIL-Na in predicting 1-month (p = 0.0493) and 3-month mortality (p = 0.0225). Conclusions: Compared to CP and MELD, MELD-GRAIL-Na was found to be a better and more useful system for evaluating short-term (1- and 3-month) mortality in Korean patients with cirrhosis, especially those with advanced cirrhosis (CP class B and C).

Switching from Tenofovir-Based Combination Therapy to Tenofovir Monotherapy in Multidrug-Experienced Chronic Hepatitis B Patients: a 5-Year Experience at Two Centers.

Patients with chronic hepatitis B (CHB) who were administered tenofovir disoproxil fumarate (TDF)-based combination therapy after receiving multiple drugs are frequently switched to TDF monotherapy in South Korea. We evaluated the efficacy and safety of switching to TDF monotherapy from TDF-based combination therapy over 5 years. This was a retrospective study of multidrug-experienced CHB patients who switched from TDF-based combination therapy to TDF monotherapy after achieving a virologic response (VR; <20 IU/mL) at Konkuk University Hospital and Sanggye Paik Hospital. The biochemical response was defined as a normalized serum ALT level during follow-up. Each patient was assessed from the date of switching to TDF monotherapy to the date of the last follow-up over 5 years. A total of 39 patients who received at least one antiviral therapy before TDF-based combination therapy were analyzed. The median duration of VR before switching to TDF monotherapy was 18 months and the median duration of TDF monotherapy was 55 months. In this study, except for one patient who had poor compliance, all patients maintained a VR. Three patients had a temporarily increased HBV DNA level and 91.2% of the patients showed a biochemical response. Switching multidrug-experienced patients to TDF monotherapy is generally safe and effective.

Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study.

OBJECTIVE: Direct comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study. DESIGNS: This multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance: 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC). RESULTS: During follow-up (median=26.9 months, IQR=12.2-49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38). CONCLUSION: The discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA.

Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors.

GOALS: We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF). BACKGROUND: The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known. STUDY: A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition. RESULTS: The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode. CONCLUSIONS: A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.

Three types of preS1 start codon deletion variants in the natural course of chronic hepatitis B infection.

BACKGROUND AND AIM: Naturally occurring hepatitis B virus variants carrying a deletion in the preS1 start codon region may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The aim of this study was to determine the immune phase-specific prevalent patterns of preS1 start codon deletion variants and related factors during the natural course of CHB. METHODS: A total of 399 CHB patients were enrolled. Genotypic analysis of three different preS1 start codon deletion variants (classified by deletion size: 15-base pair [bp], 18-bp, and 21-bp deletion variants) was performed. RESULTS: PreS1 start codon deletion variants were detected in 155 of 399 patients (38.8%). The predominant variant was a 15-bp deletion in the immune-tolerance phase (18/50, 36%) and an 18-bp deletion in the immune-clearance phase (69/183, 37.7%). A 21-bp deletion was the predominant variant in the low replicative phase (3/25, 12.0%) and reactivated hepatitis Be antigen (HBeAg)-negative phase (22/141, 15.6%). The 15-bp and 18-bp deletion variants were more frequently found in HBeAg-positive patients (P < 0.010 and P < 0.001, respectively), whereas the 21-bp deletion variant was more frequently found in HBeAg-negative patients (P < 0.001). On multiple logistic regression analyses, the 21-bp deletion variant was independently associated with liver cirrhosis (P = 0.006), and the 15-bp deletion variant was significantly related to an incomplete response to antiviral agents (P = 0.012). CONCLUSIONS: The predominant type of preS1 start codon deletion variants changes according to the immune phases of CHB infection, and each variant type is associated with different clinical parameters. PreS1 start codon deletion variants might interact with the host immune response differently according to their variant types.

Validation of prognostic scores to predict short-term mortality in patients with acute-on-chronic liver failure.

BACKGROUND AND AIM: The aim of this study was to validate the chronic liver failure-sequential organ failure assessment score (CLIF-SOFAs), CLIF consortium organ failure score (CLIF-C OFs), CLIF-C acute-on-chronic liver failure score (CLIF-C ACLFs), and CLIF-C acute decompensation score in Korean chronic liver disease patients with acute deterioration. METHODS: Acute-on-chronic liver failure was defined by either the Asian Pacific Association for the study of the Liver ACLF Research Consortium (AARC) or CLIF-C criteria. The diagnostic performances for short-term mortality were compared by the area under the receiver operating characteristic curve. RESULTS: Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF-C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The areas under the receiver operating characteristic of the CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs were significantly higher than those of the Child-Pugh, model for end-stage liver disease, and model for end-stage liver disease-Na scores in ACLF patients according to the CLIF-C definition (all P < 0.05), but there were no significant differences in patients without ACLF or in patients with ACLF according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs had higher specificities with a fixed sensitivity than liver specific scores in ACLF patients according to the CLIF-C definition, but not in ACLF patients according to the AARC definition. CONCLUSIONS: The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF-C definition, but not the AARC definition.

Endoscopic Submucosal Dissection of Early Gastric Cancer in Patients with Liver Cirrhosis.

BACKGROUND AND OBJECTIVES: Endoscopic submucosal dissection (ESD) has become widely accepted method for treating early gastric cancer (EGC), but little is known about its role in patients with liver cirrhosis (LC). The aims of this study were to evaluate the outcomes of ESD in treating EGC in patients with LC. METHODS: The multicenter retrospective study identified 43 patients with chronic hepatitis B (CHB)-related cirrhosis undergoing ESD for treating EGC. The patients (LC group) were subdivided into two groups based on their Child-Pugh classification (CP-class): 32 with CP-class A (LC-A) and 11 with CP-class B (LC-B). The patients were compared to 47 non-cirrhotic CHB patients who underwent ESD (CHB group). Eight patients had a past history of hepatocellular carcinoma (HCC) prior to ESD, but no patients had viable HCC when ESD was performed. RESULTS: Procedural outcomes (en bloc, lateral/basal margins resection) and post-procedural complications (bleeding or perforation) did not differ significantly between the LC and CHB groups or between the LC-A and LC-B groups. No patients experienced worsening of the Child-Pugh score 1 month after ESD compared with the baseline score. During a median observation period of 66 months, the recurrence rates of gastric cancers were similar between the LC and CHB groups (5-year recurrence rates: 2.4 vs. 2.3%, p = 0.925), and all recurrent gastric cancers were completely resected by additional ESD. The overall mortality rate was increased in the LC group (5-year mortality rates: 17.9 vs. 5.7%, p = 0.034), and 8 of 10 deaths were attributed to liver-related diseases (such as HCC, complications of portal hypertension, hepatic failure). CONCLUSIONS: ESD is feasible in patients with EGC and comorbid LC, even those with CP-class B cirrhosis. Their prognosis depends on LC-related diseases and not recurrent EGC.

Prognosis of Spontaneous Bacterial Peritonitis in Hepatocellular Carcinoma Patients.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious infectious complication in patients with liver cirrhosis. However, information about prognosis of SBP in hepatocellular carcinoma (HCC) patients is limited. We investigated the clinical course of SBP in HCC patients. METHODS: This study enrolled patients diagnosed with SBP between 2005 and 2017. Medical records of patients were reviewed and clinical course was compared between the non-HCC and HCC groups. RESULTS: In total, 123 SBP cases including 49 HCC cases were enrolled. Men were predominant (48/74, 64.9% vs. 34/49, 69.4%; P = 0.697); median age was 58 years in both non-HCC and HCC groups (P = 0.887). The most common etiology was alcohol (32/74, 43.2%) in non-HCC group and hepatitis B (30/49, 61.2%) in HCC group (P = 0.009). Antibiotic resistance rate was higher in non-HCC than in HCC group (29.7% vs. 12.2%; P = 0.028); in-hospital mortality did not differ between the groups (25/74, 33.8% vs. 13/49, 26.5%; P = 0.431). Development rate of hepatorenal syndrome did not differ between non-HCC and HCC group (14/74, 18.9% vs. 10/49, 20.4%; P = 1.000), but hepatic encephalopathy was less common in HCC group (26/74, 35.2% vs. 9/49, 18.3%; P = 0.008). The most important predictor of in-hospital mortality in patients with HCC was white blood cell count above 11,570 cells/mm3 (odds ratio, 6.629; 95% confidence interval, 1.652-26.590; P = 0.008). CONCLUSION: Prognosis of SBP in HCC patients is relatively less severe. This result may be related with reduced antibiotics resistance and lower development rates of other complications, such as hepatic encephalopathy. Degree of systemic inflammation may be the most important factor for in-hospital mortality.

Nucleos(t)ide Analogue Treatment for Patients With Hepatitis B Virus (HBV) e Antigen-Positive Chronic HBV Genotype C Infection: A Nationwide, Multicenter, Retrospective Study.

Background: Antiviral treatment for hepatitis B virus (HBV) e antigen (HBeAg)-positive chronic HBV infection is still controversial. We assessed whether antiviral treatment reduces the risk of liver disease progression in these patients. Methods: This study included consecutive patients in 8 large-volume hospitals in Korea who tested positive for HBeAg and had an HBV DNA level of >20000 IU/mL, an alanine aminotransferase (ALT) level of <40 IU/L, and no evidence of cirrhosis. The primary end point was the development of hepatocellular carcinoma (HCC), and the secondary end point was the development of cirrhosis. Results: A total of 484 patients were included: 87 were in the antiviral treatment group, and 397 were in the control group. Baseline liver function was significantly more favorable for the control group. After matching for propensity score to overcome those differences, the antiviral treatment group had a significantly reduced risk for HCC (hazard ratio [HR], 0.234; log-rank P = .046) and cirrhosis (HR, 0.235; log-rank P = .015), compared with the control group. After balancing the baseline characteristics by using inverse probability weighting, antiviral therapy significantly decreased the risk of HCC (HR, 0.189; log-rank P = .004) and cirrhosis (HR, 0.347; log-rank P = .036). Conclusion: Antiviral therapy for patients with HBeAg-positive chronic HBV infection and have a high HBV load reduces the risk of HCC, even if the ALT level is below the upper limit of normal.

Noninvasive Tests for Fibrosis Predict 5-Year Mortality and Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

GOALS: To evaluate the degree of liver fibrosis as a predictor of mortality and hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B. BACKGROUND: The level of fibrosis predicts mortality and liver-related complications. STUDY: A total of 542 patients over 18 years old with chronic hepatitis B who visited the Konkuk University Hospital between the years 2005 and 2006 were enrolled. We performed noninvasive tests of fibrosis (APRI, FIB-4) and hepatitis B virus (HBV) DNA levels. The data on mortality and newly developed HCC collected during a 5-year follow-up were analyzed. RESULTS: In 5 years, 40 patients died and 68 patients developed HCC. The area under the receiver operator characteristic (AUROC) curve of APRI, FIB-4, and HBV DNA levels for mortality was 0.760, 0.789, and 0.463, with cut-off points at 0.766, 2.671, and 3.150, respectively. The AUROC curve of APRI, FIB-4, and HBV DNA levels for HCC was 0.731, 0.803, and 0.523, with cut-off points at 0.766, 2.225, and 4.245, respectively. APRI and FIB-4 were predictors of mortality and HCC development, where patients with APRI over 0.766 had a greater risk of death [odds ratio (OR)=3.214, 95% confidence interval (CI), 1.009-10.238] and HCC development (OR=4.245, 95% CI, 1.723-10.456). Patients with FIB-4>2.671 had a higher risk of death (OR=4.431, 95% CI, 1.512-12.986) and those over 2.225 had a greater risk of developing HCC (OR=3.607, 95% CI, 1.622-8.021). CONCLUSIONS: APRI and FIB-4 may be more useful than HBV DNA level in predicting 5-year mortality and development of HCC.

Subclinical Ascites Does Not Affect the Long-term Prognosis in Hepatitis B Virus-related Cirrhosis Patients Receiving Antivirals.

BACKGROUND AND AIMS: This study evaluated the clinical significance of subclinical ascites in patients with hepatitis B virus-related cirrhosis treated with lamivudine (LMV) or entecavir (ETV). METHODS: This multicenter retrospective study involved 8 hospitals. Patients were classified by degree of ascites: (1) no ascites (no ascites on imaging, no diuretics), (2) subclinical ascites (small amount of ascites on imaging, no diuretics), and (3) clinical ascites (moderate to severe ascites or diuretics). RESULTS: Out of 501 patients, 336 (68%), 51 (10%), and 114 (23%) patients were classified as no-ascites, subclinical ascites, and clinical ascites, respectively. In all, 100 (20%) and 401 (80%) were treated with LMV and ETV, respectively. Over 58±24 months of follow-up, 105 patients (21%) developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma did not differ between LMV-treated and ETV-treated patients (P=0.61); it was higher in the clinical-ascites group than the no-ascites (P=0.054) and subclinical-ascites (P=0.03) groups, but it was comparable between the latter 2 (P=0.225). Forty-five patients (9%) died during follow-up. Survival was significantly shorter in the clinical-ascites group than the other 2 (both P<0.005), but it was comparable between no-ascites and subclinical-ascites groups (P=0.444). Multivariate analysis showed that mortality was significantly associated with prothrombin time [hazard ratio (HR)=2.42; 95% confidence interval (CI), 1.59-3.70], serum albumin (HR=0.54; 95% CI, 0.29-0.99), and presence of clinical ascites (HR=3.58; 95% CI, 1.54-8.30). CONCLUSIONS: Subclinical ascites did not affect prognosis in patients with hepatitis B virus-related cirrhosis receiving antiviral treatment.

The impact of the hepatitis B virus polymerase rtA181T mutation on replication and drug resistance is potentially affected by overlapping changes in surface gene.

UNLABELLED: The emergence of drug-resistant hepatitis B virus (HBV) is a major problem for antiviral treatment in chronic hepatitis B infection. In this study, we analyzed the evolution of drug-resistant mutations and characterized the effects of the rtA181T and rtI233V mutations on viral replication and drug resistance. We performed a clonal analysis of the HBV polymerase gene from serum samples during viral breakthrough treated with antiviral agents. A series of mutant clones containing rtA181T and/or rtI233V mutations were constructed and determined the effect of these mutations on the replication ability and drug resistance. An in vitro study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. Compared to the rtA181T surface missense mutation (rtA181T/sW172S), the introduction of rtA181T surface nonsense mutation (rtA181T/sW172*) resulted in decreased viral replication and increased drug resistance. Complementation assay revealed that the truncated PreS1 is responsible for reduced replication of rtA181T/sW172* mutant. Moreover, the rtA181T/sW172* mutant exhibited a defect in viral particle secretion. The rtI233V mutation that emerged during adefovir therapy reduced viral replication and conferred resistance to adefovir. Our data suggest that the impact of the rtA181T mutation on replication and drug resistance differs based on the mutation status of the corresponding surface gene. The rtI233V mutation also affects replication ability and drug resistance. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation. IMPORTANCE: The emergence of drug-resistant HBV that are no longer susceptible to nucleos(t)ide analogues is a major problem for antiviral treatment in chronic hepatitis B infection. Among drug-resistant mutations, the single rtA181T mutation is known to confer cross-resistance to antiviral drugs. This mutation causes intermediate or reduced susceptibility to tenofovir. Moreover, the clinical occurrence of the rtA181T mutation during antiviral therapy is also high. Our study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation. We believe that our study will not only extend the understanding of the drug resistance mechanism, but it will also ultimately provide new treatment options for patients with multidrug resistant HBV.

Diagnosis of esophageal varices on liver CT: is thin-section reconstruction necessary?

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of 1 mm, 3 mm, and 5 mm section thicknesses of liver CT on the detection and grading of esophageal varices in cirrhotic patients. METHODOLOGY: A total of 219 consecutive cirrhotic patients who had undergone both upper endoscopy and 64-channel liver CT were included. Portal phase images of each CT were reconstructed with a section thickness of 1 mm, 3 mm, and 5 mm. Four radiologists independently reviewed the 3 image sets. The observers evaluated the presence of esophageal varices on a 5-point confidence scale and measured the maximal short diameter of the largest varix identified. Sensitivity, specificity and predictive value calculation and receiver operating characteristic analysis were performed. Correlation between CT measurements and endoscopic grading as the reference standard was assessed. RESULTS: The averaged Az values at 1 mm, 3 mm, and 5 mm image sets were 0.936, 0.946, and 0.935, respectively, and they were not significantly different among the 4 observers. When a 3 mm cut-off criterion for large varices was applied, sensitivity, specificity, and predictive values were comparable among the 3 image datasets. CONCLUSIONS: Routine liver CT protocol is sufficient for evaluation of esophageal varices in cirrhotic patients without adding thin section reconstruction images.

Model for end-stage liver disease-3.0 vs. model for end-stage liver disease-sodium: mortality prediction in Korea.

BACKGROUND/AIMS: The model for end-stage liver disease (MELD) serves as an indicator for short-term mortality among patients diagnosed with liver cirrhosis (LC) and is used to prioritize patients for liver transplantation. In 2021, the updated version of MELD, MELD-3.0, was introduced to improve the accuracy of the mortality prediction of MELD. Therefore, this study aimed to compare the efficacy of MELD 3.0 and MELD-Na in predicting mortality among Korean patients with LC. METHODS: A retrospective review was conducted using the medical records of patients diagnosed with LC who were admitted to Konkuk University Hospital From 2011 to 2021. The study calculated the predictive values of MELD-Na and MELD-3.0 for 3- and 6-months mortality using the area under the receiver operating curve (AUROC) and compared the results using the DeLong test. RESULTS: Of the 3,034 patients enrolled in the study, 339 (11.2%) died within 3 months and 421 (14.4%) died within 6 months. The AUROCs values for predicting 3 months mortality were 0.846 for MELD-Na and 0.851 for MELD-3.0. The corresponding AUROC values for predicting 6 months mortality were 0.843 for MELD-Na and 0.848 for MELD-3.0. MELD-3.0 exhibited better discrimination ability than MELD-Na for both 3 (p = 0.03) and 6 months mortality (p = 0.01). CONCLUSION: Our study found a significant difference between the performance of MELD-3.0 and MELD-Na in Korean patients with LC.

Risk for coronary heart disease increases risk for colorectal neoplasm.

BACKGROUND & AIMS: Colorectal neoplasms and coronary artery disease have similar risk factors. Patients with established coronary artery disease have a high prevalence of colorectal neoplasms. However, little is known about the risk of colorectal neoplasms among individuals at risk for coronary artery disease. METHODS: We performed a cross-sectional study of 3144 asymptomatic, average-risk individuals without history of coronary artery disease or other vascular disorders who received a screening colonoscopy examination from January to December 2010 at Konkuk University Medical Center in Seoul, Korea. Participants were classified as having low (<10%), intermediate (10%-20%), or high (≥20%) risk for developing coronary artery disease in the next 10 years, which was based on Framingham/Adult Treatment Panel III risk scores. RESULTS: The prevalence of colorectal neoplasms in subjects with low, intermediate, and high risk for coronary artery disease was 25.6% (635/2485), 46.6% (252/541), and 53.4% (63/118), respectively (P < .001); the prevalence of advanced colorectal neoplasms was 4.9% (122/2485), 9.2% (50/541), and 17.8% (21/118), respectively, for these subjects (P < .001). In multivariate analyses, the high-risk group had a significantly increased risk of advanced colorectal neoplasm (odds ratio, 3.31; 95% confidence interval [CI], 1.94-5.65), compared with the low-risk group. The numbers of colonoscopies needed to identify individuals with advanced colorectal neoplasms in intermediate-risk and high-risk groups were 10.8 (95% CI, 8.6-14.7) and 5.6 (95% CI, 7.6-11.9), respectively, which were significantly lower than for the low-risk group (20.4; 95% CI, 17.4-24.6). CONCLUSIONS: The prevalence and the risk of overall and advanced colorectal neoplasms increase with risk of coronary artery disease. Individuals with a 10-year risk of coronary artery disease ≥10% might benefit from colonoscopy screening, but further studies are needed to confirm and generalize these results.

Predictive value of Refit Model for End-Stage Liver Disease, Refit Model for End-Stage Liver Disease-Na, and pre-existing scoring system for 3-month mortality in Korean patients with cirrhosis.

BACKGROUND AND AIM: The Model for End-Stage Liver Disease (MELD) has been widely used for predicting short-term mortality in patients with cirrhosis in the U.S. A modification of the MELD score was published in 2011. This was validated for Korean patients with cirrhosis. METHODS: The medical records of patients with cirrhosis who were admitted to Konkuk University Hospital from 2006 to 2010 were retrospectively reviewed. The predictive value for 3-month mortality was compared between the Refit MELD, Refit MELD-Na, MELD, MELD-Na, and Child-Pugh score. The comparison was performed by calculating the area under the receiver operating curve (AUROC). RESULTS: A total of 882 patients were enrolled and 77 (8.7%) died within 3 months. The most common etiology was alcohol (45.4%) followed by hepatitis B (34.2%). The AUROCs of the Refit MELD, Refit MELD-Na, MELD, MELD-Na, and Child-Pugh score were 0.842, 0.817, 0.844, 0.848, and 0.831, respectively. The Refit MELD-Na showed a lower value than MELD-Na (P = 0.0005), MELD (P = 0.0190), and the Refit MELD (P = 0.0174). When the patients with hepatitis B, C, and alcoholic cirrhosis were analyzed, the AUROCs were 0.960, 0.920, 0.953, 0.951, 0.896, 0.959, 0.956, 0.947, 0.956, 0.943, and 0.746, 0.707, 0.752, 0.747, 0.755. CONCLUSIONS: The improvement in predictive value for 3-month mortality was not definite. The Refit MELD-Na especially showed the lowest value. This result may have been due to differences in underlying etiology of cirrhosis between Korea and the U.S. Thus, a larger prospective study is warranted.

Locked nucleic acid real-time polymerase chain reaction method identifying two polymorphisms of hepatitis B virus genotype C2 infections, rt269L and rt269I.

BACKGROUND: The presence of two distinct hepatitis B virus (HBV) Pol RT polymorphisms, rt269L and rt269I, could contribute to the unique clinical or virological phenotype of HBV genotype C2. Therefore, a simple and sensitive method capable of identifying both types in chronic hepatitis B (CHB) patients infected with genotype C2 should be developed. AIM: To develop a novel simple and sensitive locked nucleic acid (LNA)-real time-polymerase chain reaction (RT-PCR) method capable of identifying two rt269 types in CHB genotype C2 patients. METHODS: We designed proper primer and probe sets for LNA-RT-PCR for the separation of rt269 types. Using synthesized DNAs of the wild type and variant forms, melting temperature analysis, detection sensitivity, and endpoint genotyping for LNA-RT-PCR were performed. The developed LNA-RT-PCR method was applied to a total of 94 CHB patients of genotype C2 for the identification of two rt269 polymorphisms, and these results were compared with those obtained by a direct sequencing protocol. RESULTS: The LNA-RT-PCR method could identify two rt269L and rt269I polymorphisms of three genotypes, two rt269L types ['L1' (WT) and 'L2'] and one rt269I type ('I') in single (63 samples, 72.4%) or mixed forms (24 samples, 27.6%) in 87 (92.6% sensitivity) of 94 samples from Korean CHB patients. When the results were compared with those obtained by the direct sequencing protocol, the LNA-RT-PCR method showed the same results in all but one of 87 positive detected samples (98.9% specificity). CONCLUSION: The newly developed LNA-RT-PCR method could identify two rt269 polymorphisms, rt269L and rt269I, in CHB patients with genotype C2 infections. This method could be effectively used for the understanding of disease progression in genotype C2 endemic areas.

Prospective, randomized, back-to-back trial evaluating the usefulness of i-SCAN in screening colonoscopy.

BACKGROUND: The newly developed i-SCAN application can theoretically maximize the effectiveness of colonoscopy. However, the practical usefulness of the i-SCAN application during screening colonoscopy has not been assessed. OBJECTIVE: To assess the efficacy of the i-SCAN application during screening colonoscopy. DESIGN: A prospective, randomized trial that used a modified, back-to-back colonoscopy. SETTING: Academic hospital. PATIENTS: This study involved 389 asymptomatic, consecutive, average-risk patients who underwent screening colonoscopy. INTERVENTION: The patients were randomized to the first withdrawal with either conventional high-definition white light (HDWL group; n = 119), i-SCAN contrast/surface enhancement (CE/SE) mode (i-SCAN1 group; n = 115), or i-SCAN CE/SE/tone enhancement-colorectal mode (i-SCAN2 group; n = 118). All patients underwent a second examination with HDWL as the criterion standard. MAIN OUTCOME MEASUREMENTS: The primary outcome measurement was the adenoma detection rate and adenoma miss rate. The secondary outcome measurement was the accuracy of the histologic prediction of neoplastic and nonneoplastic polyps. RESULTS: The adenoma detection rates during the first withdrawal of HDWL, i-SCAN1, and i-SCAN2 were 31.9%, 36.5%, and 33.1%, respectively (P = .742), and the adenoma miss rates of each group were 22.9%, 19.3%, and 15.9%, respectively (P = .513). Based on the multivariate analysis, the application of i-SCAN was not associated with an improvement in adenoma detection and the prevention of missed polyps. However, the prediction of neoplastic and nonneoplastic colorectal lesions was more precise in the i-SCAN2 group compared with the HDWL group (accuracy 79.3% vs 75.5%, P = .029; sensitivity 86.5% vs 72.6%, P = .020; and specificity 91.4% vs 80.6%, P = .040). LIMITATIONS: Single-center trial. CONCLUSION: i-SCAN during the screening colonoscopy may fail to improve adenoma detection and the prevention of missed polyps, but i-SCAN appears to be effective for real-time histologic prediction of polyps compared with conventional HDWL colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01417611.).

Long-term impact of entecavir monotherapy in chronic hepatitis B patients with a partial virologic response to entecavir therapy.

OBJECTIVE: Partial virologic response (PVR) in chronic hepatitis B (CHB) patients during antiviral therapy is associated with an increased risk of occurrence of viral resistance and treatment failure. The aim of this study was to evaluate the clinical and virological responses of partial responders to long-term entecavir (ETV) monotherapy. MATERIAL AND METHOD: In this open-labeled prospective study, 128 treatment-naïve CHB patients treated with 0.5 mg ETV once daily for more than 12 months were monitored at baseline and at 3-month intervals during treatment. RESULTS: At baseline, the mean age of subjects was 47.0 ± 13.0 years, and the median duration of treatment was 27 months; 85 subjects (66.4%) were HBeAg-positive, and 47 patients (36.7%) had liver cirrhosis. Eighteen of 128 patients (14.0%) showed PVR to 48 weeks of ETV treatment, and 13 patients were followed up for over 24 months. Among them, 9 of 13 patients (69.2 %) achieved a complete virologic response (VR, HBV-DNA < 60 IU/mL) during prolonged ETV treatment. Four showed persistent PVR, but only one patient with poor compliance developed genetic resistance to ETV at month 27. The occurrence of PVR was independently associated with a high viral load, more than 7 log(10) IU/mL (p = 0.014). CONCLUSIONS: CHB patients with a high viral load, more than 7 log log(10) IU/mL, are related to the occurrence of PVR during ETV monotherapy. Long-term ETV monotherapy may be effective for suppressing serum HBV DNA levels in treatment- naïve CHB patients with a PVR to ETV.