Tenofovir disoproxil fumarate versus tenofovir alafenamide on risk of osteoporotic fracture in patients with chronic hepatitis B: A nationwide claims study in South Korea.

BACKGROUND: As tenofovir disoproxil fumarate (TDF) requires long-term use, a reduction in bone density should be considered a possibility when treating patients with chronic hepatitis B (CHB) with aging and systemic diseases. Patients treated with tenofovir alafenamide (TAF) have improved bone mineral density loss compared to patients treated with TDF. Although improvements in bone density caused by TAF have been reported, studies on the actual reduction of fractures are insufficient. AIM: To evaluate the impact of TAF on the risk of osteoporotic fractures in comparison with that of TDF. METHODS: Using the national claims data of the Health Insurance Review and Assessment Service, we conducted a retrospective cohort study of 32,582 patients with CHB who had been initially treated with TDF or TAF between November 2017 and December 2020. The numbers of patients treated with TDF and TAF were 20,877 and 11,705, respectively. The annual fracture rate per 100 patients in each group was calculated, and the Cox proportional hazard ratio (HR) was analysed after applying inverse probability treatment weights (IPTW) for both groups. RESULTS: Among 32,582 patients, the average age was 47.8 ± 11.2 years, 64.5% were men, and the follow-up period was 24.4 ± 11.6 months. The incidence of osteoporotic fractures was 0.78 and 0.49 per 100 person-years in the TDF and TAF groups, respectively. After application of IPTW, the HR was 0.68 (95% confidence interval 0.55-0.85, p = 0.001). CONCLUSION: TAF-treated patients with CHB had a significantly lower risk of osteoporotic fracture than TDF-treated patients.

A model for predicting poor survival in patients with cirrhosis undergoing portosystemic shunt embolization.

BACKGROUND AND AIM: Portosystemic shunt embolization (PSSE) is a promising treatment for hepatic encephalopathy (HEP) and gastric varix (GV) in cirrhotic patients with a spontaneous portosystemic shunt. However, PSSE may worsen portal hypertension causing hepatorenal syndrome, liver failure, and mortality. This study aimed to develop and validate a prognostic model that helps identify patients with a risk of poor short-term survival after PSSE. METHODS: We included 188 patients who underwent PSSE for recurrent HEP or GV at a tertiary center in Korea. To develop a prediction model for 6-month survival after PSSE, Cox proportional-hazard model was used. The developed model was validated in a separate cohort of 184 patients from two other tertiary centers. RESULTS: In multivariable analysis, the 1-year overall survival after PSSE was significantly associated with baseline levels of serum albumin, total bilirubin, and international normalized ratio (INR). We therefore developed the albumin-bilirubin-INR (ABI) score by assigning 1 point each for albumin < 3.0 g/dL, total bilirubin ≥ 1.5 mg/dL, and INR ≥ 1.5. Time-dependent areas under the curve of the ABI score for predicting 3-month and 6-month survival were 0.85 and 0.85 in the development cohort and 0.83 and 0.78 in the validation cohort, indicating good discrimination performance. The ABI score showed a better discrimination and calibration performance than the model for end-stage liver disease and the Child-Pugh scores, especially in high-risk patients. CONCLUSIONS: The ABI score is a simple prognostic model that helps decide whether to proceed with PSSE for the prevention of HEP or GV bleeding in patients with spontaneous portosystemic shunt.

Clinical Outcomes and Validation of Ursodeoxycholic Acid Response Scores in Patients with Korean Primary Biliary Cholangitis: A Multicenter Cohort Study.

Background/Aims: The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. Methods: A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. Results: After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCA response rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41 (n=97). The area under the receiver operating characteristic curve of URS in predicting UDCA response was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5 years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed according to the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). Conclusions: URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.

Validation of MELD 3.0 scoring system in East Asian patients with cirrhosis awaiting liver transplantation.

Recently, a new predictive model that jointly considers the Model of End-stage Liver Disease (MELD) 3.0 and albumin has been proposed. This study investigated the performance of the MELD 3.0 score in predicting the 3-month survival of East Asian patients with cirrhosis compared with the other MELD-based scores. Validation was performed with the retrospective data of 2153 patients in South Korea who were listed for liver transplantation (LT). Discrimination and calibration analyses were performed using the MELD-based scores as an independent variable. On average, patients had the original MELD score of 18.70 ± 9.65. Alcohol (39.99%) and chronic HBV (38.55%) were the 2 main etiologies. The MELD 3.0 with albumin showed slightly better discrimination [c-index = 0.738, incremental AUC (iAUC) = 0.719] compared with the MELD 3.0 without albumin (c-index = 0.737, iAUC = 0.715), MELD-Na (c-index = 0.730, iAUC = 0.707), or the original MELD (c-index = 0.718, iAUC = 0.687) for predicting 3-month survival but not significantly different compared with prior models. Likewise, in the stratified analysis according to the strata of MELD, although the performance of MELD 3.0 was better throughout all the MELD strata than MELD original, there was no statistical difference in performance. The MELD 3.0 with albumin reclassified 22.61% of cases classified by the original MELD to higher MELD score categories, and there was no significant difference in the reclassification rate between males and females. The predictive power of the MELD-based system is lower in Asian populations than in western countries. Nonetheless, the MELD 3.0 score with albumin was significantly better in predicting the short-term prognosis of East Asian patients on the LT waitlist than the current allocation system, original MELD.

Recurrence of hepatocellular carcinoma in noncirrhotic patients with nonalcoholic fatty liver disease versus hepatitis B infection.

BACKGROUND AND AIMS: This study aimed to compare the long-term cumulative recurrence rates of hepatocellular carcinoma (HCC) and prognosis after curative resection for HCC in noncirrhotic patients with nonalcoholic fatty liver disease (NAFLD) versus hepatitis B virus (HBV) infection. METHODS: We retrospectively analyzed the data of 791 patients without recurrence within 1 year after curative resection for HCC from January 2005 to December 2015. Of these, 63 and 728 were NAFLD and HBV patients without cirrhosis, respectively. RESULTS: Recurrence of HCC was observed in 6 (9.5%) and 210 (28.8%) patients in the NAFLD and HBV groups, respectively, during median follow-ups of 69.9 and 85.2 months. Cumulative recurrence rates in the NAFLD group at 2, 4, 6, 8 and 10 years (3.6, 9.4, 12.4, 12.4 and 12.4%, respectively) were significantly lower than in the HBV group (1.7, 16.9, 27.2, 37.1 and 44.4%, respectively) ( P = 0.008). Cumulative overall survival (OS) rates in the NAFLD group at 2, 4, 6, 8 and 10 years (98.2, 96.0, 84.0, 84.0 and 84.0 %, respectively) were significantly lower than in the HBV group (99.3, 98.4, 97.3, 95.7 and 93.6%, respectively) ( P = 0.003). HBV infection, with or without fatty liver compared to NAFLD, were significant predictors for the recurrence of HCC ( P < 0.05 for all) and OS ( P < 0.05 for all), respectively. CONCLUSIONS: Noncirrhotic NAFLD patients showed lower recurrence rates of HCC but poorer survival outcomes than noncirrhotic HBV patients with or without fatty liver. The recurrence risk of HCC remains even in noncirrhotic NAFLD patients.

Addition of Kidney Dysfunction Type to MELD-Na for the Prediction of Survival in Cirrhotic Patients Awaiting Liver Transplantation in Comparison with MELD 3.0 with Albumin.

It is well known that renal dysfunction has a devastating effect on the prognosis of liver cirrhosis. In this study, the aim was to assess whether the incorporation of the kidney dysfunction type into the MELD-Na score enhances its predictive capacity for outcomes in patients awaiting liver transplantation (LT), compared to utilizing the MELD 3.0 score with albumin. In total, 2080 patients awaiting the LT were enrolled at two tertiary care institutions in Korea. Discrimination abilities were analyzed by using Harrell's c-index and iAUC values between MELD-Na-kidney dysfunction type (MELD-Na-KT) and MELD 3.0 with albumin. Clinical endpoints encompassed 3-month survival, 3-month transplant-free survival (TFS), overall survival (OS), and total TFS. Out of the total of 2080 individuals, 669 (32.16%) were male. Regarding the types of renal function impairment, 1614 (77.6%) were in the normal group, 112 (5.38%) in the AKD group, 320 (15.35%) in the CKD group, and 34 (1.63%) were in the AKD on CKD group. MELD 3.0 with albumin showed better discrimination (c-index = 0.714) compared to MELD-Na-KT (c-index = 0.708) in predicting 3-month survival. Similar results were observed for OS, 3-month TFS, and total TFS as well. When divided by sex, MELD 3.0 with albumin showed the comparable prediction of 3-month survival to MELD-Na-KT (c-index 0.675 vs. 0.671, p-value 0.221) in males. However, in the female group, MELD 3.0 with albumin demonstrated better results compared to MELD-Na-KT (c-index 0.733 vs. 0.723, p-value 0.001). The integration of kidney dysfunction types into the MELD-Na did not yield superior prognostic results compared to the MELD 3.0 score with albumin. Rather, in the female group, the MELD 3.0 score with albumin was better able to predict survival. These findings suggest that laboratory values pertaining to liver dysfunction or creatinine levels may be more significant than the type of kidney dysfunction when predicting the short-term prognosis of LT candidates.

Imaging features of hepatobiliary MRI and the risk of hepatocellular carcinoma development.

OBJECTIVE: This study aimed to determine whether hepatocellular carcinoma (HCC) risk and time to HCC development differ according to hepatobiliary magnetic resonance imaging (MRI) findings among people at risk for developing HCC. MATERIALS AND METHODS: A total of 199 patients aged 40 years or older with liver cirrhosis or chronic liver disease who underwent gadoxetic acid-enhanced hepatobiliary MRI between 2011 and 2015 were analyzed. An independent radiologist retrospectively reviewed MRI findings, blinded to clinical information, and categorized them into low-risk features, high-risk features and high-risk nodules. High-risk features were defined as liver cirrhosis diagnosed by imaging. High-risk nodules were defined as LR-3 or LR-4 nodules based on LI-RADS version 2018. The primary outcome was development of HCC within 5-year of MRI evaluation. RESULTS: HCC was diagnosed in 28 patients (14.1%). HCC development was null for those with low-risk features (n = 84). The cumulative incidence rates of HCC were 0%, 2.3%, 13.4% and 22.1% at 1-, 2-, 3- and 5-year for those with high-risk features (n= 64), and were 19.1%, 31.8%, 37.3% and 46.7% at 1-, 2-, 3- and 5-year for those with high-risk nodules (n= 51). Among 28 patients developed HCC, the median time from baseline MRI to HCC diagnosis was 33.1 months (interquartile range: 25.9-46.7 months) for high-risk feature group, and 17.3 months (interquartile range: 6.2-26.5 months) for high-risk nodule group. CONCLUSIONS: HCC risk and time to HCC development differ according to baseline hepatobiliary MRI findings, indicating that hepatobiliary MRI findings can be used as biomarkers to differentiate HCC risk.

Clinical Outcomes and Adverse Events of Gastric Endoscopic Submucosal Dissection of the Mid to Upper Stomach under General Anesthesia and Monitored Anesthetic Care.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) of gastric tumors in the mid-to-upper stomach is a technically challenging procedure. This study compared the therapeutic outcomes and adverse events of ESD of tumors in the mid-to-upper stomach performed under general anesthesia (GA) or monitored anesthesia care (MAC). METHODS: Between 2012 and 2018, 674 patients underwent ESD for gastric tumors in the midbody, high body, fundus, or cardia (100 patients received GA; 574 received MAC). The outcomes of the propensity score (PS)-matched (1:1) patients receiving either GA or MAC were analyzed. RESULTS: The PS matching identified 94 patients who received GA and 94 patients who received MAC. Both groups showed high rates of en bloc resection (GA, 95.7%; MAC, 97.9%; p=0.68) and complete resection (GA, 81.9%; MAC, 84.0%; p=0.14). There were no significant differences between the rates of adverse events (GA, 16.0%; MAC, 8.5%; p=0.18) in the anesthetic groups. Logistic regression analysis indicated that the method of anesthesia did not affect the rates of complete resection or adverse events. CONCLUSION: ESD of tumors in the mid-to-upper stomach at our high-volume center had good outcomes, regardless of the method of anesthesia. Our results demonstrate no differences between the efficacies and safety of ESD performed under MAC and GA.

Clinical Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients with Undetectable Serum HBV DNA Levels.

BACKGROUND AND AIMS: Some hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients show undetectable serum HBV DNA levels at HCC diagnosis. The risk of HBV reactivation and its impact on clinical outcomes are not well-unknown. METHODS: This retrospective cohort study included a total of 985 HBV-related HCC patients with undetectable serum HBV DNA levels (< 12 IU/mL) at HCC diagnosis (112 were antiviral treatment (AVT)-naïve; 873 were receiving AVT). Incidence and risk factors for HBV reactivation (re-detection of HBV DNA in serum) during follow-up, as well as its association to overall survival, were assessed. RESULTS: During a median of 33.4 months of follow-up (range: 0.2-124.2 months), HBV reactivation was observed in 279 patients. HBV reactivation rate was significantly lower for patients receiving AVT than AVT-naïve patients (three-year cumulative incidence rate: 27.3% versus 56.0%; P < 0.001). In multivariable-adjusted analysis, the risk of HBV reactivation was lower for those receiving AVT compared to AVT-naïve patients (adjusted hazard ratio: 0.39, 95% confidence interval: 0.29-0.54). Overall survival was significantly lower for those experiencing HBV reactivation than those who did not (71.5% and 85.7% at five-year) and was associated with higher risk of overall mortality (adjusted hazard ratio: 5.15, 95% confidence interval: 3.60-7.38). CONCLUSION: More than half of AVT-naïve patients experienced HBV reactivation within three years, which was associated with increased risk of overall mortality. The risk of HBV reactivation was lower for those receiving AVT, suggesting that prompt AVT needs to be considered for AVT naïve HBV-related HCC patients with undetectable HBV DNA levels.

Comparison of EUS and ERCP-guided tissue sampling in suspected biliary stricture.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are commonly used diagnostic modalities in biliary strictures. We compared the diagnostic yield of EUS and ERCP-based tissue sampling in intrinsic biliary strictures without extrinsic mass outside the bile duct. METHODS: A total of 85 patients who underwent ERCP and EUS for diagnosis of suspected biliary strictures confined to the bile duct were analyzed retrospectively at Samsung Medical Center, Seoul, Korea, between 2010 and 2018. RESULTS: Seventy-one patients were diagnosed with malignancy and 14 patients were diagnosed with benign strictures. EUS-based tissue sampling was more sensitive and accurate than ERCP-based tissue sampling (p = 0.038). The overall sensitivity and accuracy were 67.6% (95% confidence interval (CI) 56.1-77.3) and 72.9% (95% CI 62.7-81.2) for ERCP-based sampling, and 80.3% (95% CI 69.6-87.9) and 83.5% (95% CI 74.2-89.9) for EUS-based sampling, respectively. EUS-based sampling was superior to ERCP-based sampling in distal bile duct strictures (accuracy: 87.0% vs. 72.5%, p = 0.007), but not in perihilar strictures. In cases without intraductal mass, EUS-based tissue sampling was also superior to ERCP-based sampling (accuracy: 83.3% vs. 69.7%, p = 0.029), but not in cases with mass. CONCLUSION: EUS-based tissue sampling was superior to ERCP-based method in intrinsic biliary stricture with no mass outside the bile duct, particularly in those without intraductal mass or those with strictures located in distal bile duct. Therefore, EUS-based sampling should be considered for making a pathological diagnosis of suspected distal bile duct strictures even in lesions without definite mass.

Clinical Characteristics of Clonorchis sinensis-Associated Cholangiocarcinoma: A Large-Scale, Single-Center Study.

Background: Clonorchis sinensis (CS) infection is considered a group 1 carcinogen of cholangiocarcinoma (CCA). There were very few studies regarding clinical characteristics of CS-associated CCA (CACC). This study aimed to investigate clinical characteristics of patients with CCA with or without CS infection. Methods: A total of 367 patients diagnosed with CCA who underwent diagnostic tests for CS infection were enrolled. CS infection was defined as follows: at least one positive serum ELISA test, skin test, stool microscopy, or bile microscopy. Results: There were 95 (26%) patients with CS infections. The median follow-up duration was 14.9 months (range, 6.07-36.17). The following significant differences were noted among patients with CACC compared to non-CACC; diagnosis at younger age (median 62 years vs. 65 years, p = 0.018), higher male to female ratio (83.2 vs. 61.8%, p < 0.001), and residence in CS-endemic area (46.3 vs. 25.4%, p = 0.014). Univariate analysis of prognostic factors indicated that tumor location, curative resection, tumor stage, and laboratory tests including CA 19-9, CEA, and bilirubin were significantly associated with overall survival, but CS infection was not. In multivariate analysis, tumor location, CEA, curative resection and tumor stage were identified as independent prognostic factors. Among patients under age 64, CACC group had lower survival rate than non-CACC group (p = 0.022). Conclusions: CACC had the following significant characteristics compared to non-CACC; diagnosis at younger age, higher male to female ratio, higher prevalence in CS endemic areas and poorer overall survival in patients under age 64.