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Central bank independence (CBI) has been widely advocated as a means to address the time‐inconsistency problem of controlling inflation. Consequently, many countries have embraced central bank reforms since the 1990s. While extant research in political science has sought to unveil the consequences of CBI, there remains an unexplained variation in the response of countries with regard to capital account openness. Notably, a positive association exists between CBI and capital account openness due to the constraints CBI places on leaders' discretionary monetary and fiscal policies, thereby fostering reliance on financial policy to boost their economies. However, this relationship is contingent on the domestic political contexts of countries. CBI leads to capital account liberalization only when the rule of law is guaranteed, given that CBI is often stipulated by laws. Therefore, in countries where political leaders can easily override formal rules, CBI shows no discernible impact on capital account openness. Employing two‐way fixed‐effects and error‐correction models, the study reveals that CBI increases capital account openness only in democracies, in the presence of multiple veto players, and a high level of transparency. The findings underscore the pivotal role of the domestic political environment in analyzing how CBI constrains political leaders. [ABSTRACT FROM AUTHOR]

Background and Aims: Baveno VII consensus introduced the non‐invasive criteria of clinically significant portal hypertension (CSPH) using liver stiffness measurement (LSM). We evaluated the usefulness of the Baveno VII criteria to predict the risk of decompensation in patients with compensated advanced chronic liver disease (cACLD). Methods: We conducted a retrospective cohort study of 1966 patients with cACLD. Patients were categorized into four groups (CSPH excluded (n = 619), grey zone (low risk of CSPH (n = 699), high risk of CSPH (n = 207)), and CSPH included (n = 441)) according to Baveno VII consensus. The risk of events was estimated using a Fine and Gray competing risk regression analysis, with liver transplantation and death as competing events. We calculated standardized hazard ratios (sHR) to assess the relative risk of decompensation. Results: Among 1966 patients, 178 developed decompensations over a median follow‐up of 3.06 (IQR: 1.03–6.00) years. Patients with CSPH had the highest decompensation risk, followed by the grey zone high‐risk group, grey zone low‐risk group, and those without CSPH with 3‐year cumulative risks of 22%, 12%, 3.3%, and 1.4% respectively (p <.001). Compared to CSPH excluded group, CSPH included group (sHR: 8.00, 95% CI: 4.00–16.0), grey zone high‐risk group (sHR: 6.57, 95% CI: 3.16–13.6), grey zone low‐risk group (sHR: 2.15, 95% CI: 1.04–4.41) had significantly higher risk of decompensation (Gray's test p <.01). Conclusion: Non‐invasive diagnosis of CSPH according to the Baveno VII criteria can stratify the risk of decompensation. [ABSTRACT FROM AUTHOR]

Background & Aims: Several studies suggested that efficacy of tenofovir in reducing the risk of the development of hepatocellular carcinoma (HCC) might be better than that of entecavir. It remains unknown whether a change in therapy can further reduce the risk of HCC in patients receiving entecavir therapy and achieved goal of antiviral therapy, a maintained undetectable hepatitis B virus (HBV) DNA level in the serum. Methods: A total of 1336 treatment‐naïve chronic HBV mono‐infected adult patients, who started entecavir or tenofovir treatment and achieved a maintained virologic response during follow‐up were analysed. Results: During a median 4.4 years of follow‐up (range, 1.0–7.4 years) after achieving virologic response, 99 patients developed HCC. The 5‐year cumulative HCC incidence rate was 7.3% and 6.3% for the entecavir and tenofovir groups, respectively, with similar risk of HCC between the two groups (adjusted HR, 0.82; 95% CI, 0.52–1.29; p = 0.3). The risk of HCC was similar in the propensity score‐matched cohort (HR, 1.02; 95% CI, 0.68–1.52; p = 0.94) and inverse probability treatment weighting analysis (HR, 1.11; 95% CI, 0.74–1.66; p = 0.62). In the subgroup analysis, HCC risk was similar between the two drugs in both patients with and without cirrhosis. Discussion: In patients showing maintained virologic response, no difference in the risk of HCC between entecavir and tenofovir was observed. This indicates entecavir might be as effective as tenofovir in the prevention of HCC among those patients and suggest that a change in therapy in anticipation of further reducing the risk of HCC might not be necessary for patients receiving entecavir and showing virologic response. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the on‐treatment kinetics of quantitative HBsAg during entecavir therapy to predict the treatment period needed to achieve functional cure. From a cohort of 1009 CHB treatment‐naïve patients who were started on entecavir, the kinetics of quantitative HBsAg decline was assessed in 410 patients by a linear mixed model. The difference in the kinetics of quantitative HBsAg was determined based on the HBeAg positivity, HBeAg seroclearance and presence of baseline liver cirrhosis. Among the 410 patients, 213 patients (52.0%) were HBeAg‐positive and 217 patients (66.1%) were male with a median age of 48 years. During a median follow‐up of 53.5 months, the quantitative HBsAg level showed a slow but consistent decrease. The expected log qHBsAg levels as a function of time during entecavir treatment in HBeAg(+) and HBeAg(−) patients were 3.4773‐0.0039 × Months and 3.1853‐0.0036 × Months, respectively. The estimated time to clearance of quantitative HBsAg in our study was greater than 74.1 years in HBeAg‐positive patients and 73.5 years in HBeAg‐negative patients. The calculated time to achieve functional cure is lifelong without regard to HBeAg seroclearance or presence of liver cirrhosis. The mathematical modelling from a long‐term follow‐up of chronic hepatitis B patients on entecavir shows that HBsAg clearance requires decades of treatment. Thus, lifelong therapy is inevitable in entecavir‐treated patients to achieve functional cure. [ABSTRACT FROM AUTHOR]

Nowadays, intensive immunosuppressive therapy including rituximab is commonly used prior to kidney transplantation (KT), raising concerns over hepatitis B virus (HBV) reactivation among hepatitis B surface antigen (HBsAg)‐negative and anti‐hepatitis B core (HBc)‐positive KT recipients. Recent practice guidelines suggested watchful monitoring or antiviral prophylaxis for the first 6‐12 months, the period of maximal immunosuppression. However, the actual risk for HBV reactivation, and whether short‐term antiviral therapy in the early period is necessary, remains unclear. A total of 449 HBsAg‐negative and anti‐HBc‐positive KT recipients were analysed for HBV reactivation. During a median follow‐up of 6.7 (interquartile range: 4.2‐9.4) years, HBV reactivation was observed in 9 patients (2.0%). The median time of HBV reactivation from KT was 2.8 years (range: 1.4‐11.5 years), with cumulative incidence rates of 0%, 1% and 2% for 1, 3 and 5 years, respectively. There were no severe adverse outcomes, including liver transplantation or mortality related to HBV reactivation. The risk of HBV reactivation was not high, even in anti‐HBs‐negative patients (n = 60, 4% at 5 years), ABO mismatch (n = 92, 4% at 5 years), use of rituximab (n = 66, 3% at 5 years) or plasmapheresis (n = 17, 7% at 5 years), and acute rejection (n = 169, 3% at 5 years). In conclusion, the HBV reactivation risk was not high and the time of detection was not clustered in the early post‐KT period. Our findings favour continued watchful monitoring over antiviral prophylaxis in the early period. [ABSTRACT FROM AUTHOR]

Background and Aim: Clinical course of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients presenting with low‐level viremia (LLV) is unclear. Methods: A total of 565 HBV‐related HCC patients with LLV (detectable but HBV DNA ≤ 2000 IU/mL) at the time of HCC diagnosis were analyzed. Based on patterns of HBV DNA levels during follow‐up, patients were categorized into three groups: maintained virologic remission (MVR), LLV, and flare. Overall survival was compared between those three groups. Results: During a median 4.5 years of follow‐up, 33% showed MVR, 39% showed LLV, and 28% experienced flare. The overall survival differed between MVR, LLV, and flare groups (5‐year overall survival: 74.3%, 67.3%, and 61.7%, respectively, 0.015). The patterns of HBV DNA levels were independent factors associated with overall survival, along with age, antiviral treatment, Barcelona clinic liver cancer stage, and initial treatment modality. Flare group showed increased risk of mortality (adjusted hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.15–2.55) compared with MVR group, while the risk was statistically marginal for the LLV group (adjusted HR 1.39, 95% CI 0.95–2.04). During follow‐up, 183 patients (32.4%) newly started antiviral therapy (AVT) at LLV. Flare risk was significantly lower among patients who started AVT at LLV compared with those who did not (adjusted HR 0.26, 95% CI 0.17–0.38). Conclusions: Among HBV‐related HCC patients with LLV, flare was frequent during follow‐up and was associated with poorer overall survival compared with MVR group. Prospective studies that address whether inducing MVR by early AVT improves patient outcome are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: The Baveno VI and the expanded Baveno VI criteria were proposed to help identify patients who could safely avoid screening endoscopies for clinically significant varices among patients with compensated advanced chronic liver disease. However, these criteria require cross‐validation, especially in Asian populations where the aetiologies of liver disease are different. Methods: A total of 1035 patients, including 282 patients with compensated advanced chronic liver disease of different aetiology, were analysed. The compensated advanced chronic liver disease was defined by liver stiffness measurement ≥10 kPa, Child‐Pugh class A and absence of prior liver decompensation. High‐risk varix was defined as a grade ≥2 oesophageal varix, any varix with a red colour sign or gastric varices. Results: High‐risk varixs were present in 19.5% (55/282 patients) with compensated advanced chronic liver disease. Among compensated advanced chronic liver disease patients, the expanded criteria could spare more endoscopies (51.7%) than the original criteria (27.6%). However, the expanded criteria missed a greater number of high‐risk varixs (6.8%) than the original criteria (3.8%). When stratified according to liver disease aetiology, the negative predictive values for the original Baveno VI criteria were 0.92, 1.00, 1.00 and 1.00, and the negative predictive values for the expanded criteria were 0.92, 0.96, 0.92 and 0.93 for hepatitis B, hepatitis C, alcohol and non‐alcoholic fatty liver disease, respectively. High‐risk varixs were rarely detected in patients without compensated advanced chronic liver disease (1.1%, 8/753 patients). Conclusions: In this Asian cohort study, the Baveno VI criteria were able to identify who could safely avoid screening endoscopy. The expanded Baveno VI criteria could spare more endoscopies but also could increase the odds of missing a high‐risk varix. [ABSTRACT FROM AUTHOR]

Background and Aim: We analyzed whether insulin resistance (IR) assessed by homeostasis model assessment (HOMA2-IR) index can stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B virus (HBV) infection. Methods: A retrospective cohort of 1696 chronic HBV-infected patients (age: 50.0 ± 7.8 years, men = 964 [56.8%]) who underwent detailed health checkup program including C-peptide and fasting blood glucose measurement and followed up for more than a year were analyzed. Results: During a median follow-up of 5.0 years (range, 1.0–10.5 years), 24 patients (1.4%) developed HCC. The HCC incidence rate was higher for patients with higher HOMA2-IR value than those with lower HOMA2-IR value (1.7% vs 0.5% for HOMA2-IR >1.200 vs ≤1.200, P = 0.009). HOMA2-IR was a significant factor associated with HCC development in multivariable-adjusted model (HR [95% CI]: 3.25 [1.13–9.31], adjusted for age, sex, cirrhosis, and HBV DNA levels). The association between HOMA2-IR and HCC was markedly attenuated and became no longer statistically significant (HR [95% CI]: 1.93 [0.57–6.51]) when further adjusted for obesity, hypertension, and diabetes. In subgroup analysis, HOMA2-IR value was an independent factor associated with HCC in patients without overt metabolic abnormalities (hypertension, diabetes, and metabolic syndrome) but not for those with overt metabolic abnormalities. Conclusion: Insulin resistance assessed by HOMA2 was associated with the risk of HCC, indicating that HOMA2-IR can be a useful tool for stratifying the risk of HCC in chronic HBV-infected patients, particularly in patients without overt metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Background & Aims Several staging systems have been proposed for hepatocellular carcinoma ( HCC). Among them, only the Barcelona Clinic Liver Cancer ( BCLC) and Hong Kong Liver Cancer ( HKLC) staging systems also recommend treatment modality. This study was designed to see whether BCLC and HKLC staging can guide treatment strategy, so analyzed whether patients survival is better for those who received recommended therapy by each staging system. Methods A total of 3515 treatment-naïve, newly diagnosed HCC patients at a single centre were analyzed. Results Five-year survival rates according to BCLC stages: 0 = 79.1%, A = 62.9%, B = 40.3%, C = 21.3% and D = 27.0%; 5-year survival rates according to HKLC stages: I = 72.3%, IIa = 54.9%, IIb = 50.6%, IIIa = 21.3%, IIIb = 10.2%, IVa = 16.7%, IVb = 7.2%, Va = 47.1% and Vb = 11.3%. The C-indices of the BCLC and HKLC staging systems were 0.708 and 0.732 respectively. Patient survival was better when patients received the recommended treatment in stages 0 or A; survival was worse if treatment began at stage B, C or D. For HKLC staging system, survival was better when patients received the recommended treatment in stages I, IIa, IIb, IIIa or Va but was worse when treatment began in stages IIIb, IVa, IVb or Vb. Conclusion Both the BCLC and HKLC staging systems effectively stratified patient prognosis, but neither could direct therapy for a large proportion of patients; for some stages, recommended therapy was associated with worse prognosis. [ABSTRACT FROM AUTHOR]

Background & Aims Despite increasing reports of hepatitis B virus (HBV) reactivation in multiple myeloma (MM), HBV reactivation in patients with resolved hepatitis B [hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core antigen antibody (anti-HBc)-positive] is still poorly characterized. The aim of this study was to clarify its frequency and risk factors. Methods A total of 230 MM patients with resolved hepatitis B were retrospectively reviewed for HBV reactivation and biochemical flare. Results During a median 2.4 years of follow-up, HBV reactivation was diagnosed in 12 patients (5.2%). The cumulative rates of HBV reactivation at 2 years and 5 years were 5% and 8% respectively. A baseline anti-HBs-negative status ( P = 0.033) and high-dose therapy/autologous stem-cell transplantation [HDT/ASCT ( P = 0.025)] were significant risk factors that were positively associated with HBV reactivation. In subgroup analysis of patients treated with HDT/ASCT ( n = 127), a baseline anti-HBs-negative status was the only significant risk factor for HBV reactivation (hazard ratio, 4.64; 95% CI, 1.47-14.7; P = 0.009). Discussion These data show that evaluation of anti-HBc is needed for MM patients, and suggest that monitoring of HBV DNA should be considered for patients with resolved hepatitis B undergoing HDT/ASCT, especially those who are anti-HBs-negative. [ABSTRACT FROM AUTHOR]

Background & Aims Sorafenib is regarded as the standard treatment of care in Barcelona Clinic Liver Cancer ( BCLC) stage C patients. However, the modest overall survival ( OS) and disease control rate warrants for a better treatment modality. This study aimed to investigate the feasibility of combined transarterial chemoembolization and radiotherapy ( TACE+ RT) in comparison with sorafenib for advanced hepatocellular carcinoma ( HCC). Methods and Materials From 2007 to 2011, a total of 116 patients with locally advanced HCC were retrospectively enrolled. Sixty-seven patients treated with TACE+ RT were compared with 49 patients treated with sorafenib. Propensity score matching generated a matched cohort composed of 27 patients from each group. OS was the primary endpoint for the analysis. Results At baseline, the sorafenib group had a tendency for a tumour size ≥10 cm, presence of lymph node metastasis and main portal vein tumour thrombosis compared to the TACE+ RT group. The OS in the TACE+ RT group was significantly longer compared to the sorafenib group (14.1 months vs. 3.3 months, P < 0.001). In the propensity score-matched cohort, baseline characteristics did not differ between the two groups. The TACE+ RT group showed prolonged OS compared to the sorafenib group (6.7 months vs. 3.1 months, P < 0.001). Multivariate analysis revealed that TACE+ RT was the only independent prognostic factor associated with survival in the propensity score-matched cohort ( HR = 0.172, P < 0.001). Conclusions The OS of TACE+ RT was longer compared to sorafenib treatment in locally advanced HCC patients without distant metastasis. Further prospective studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is the major cause of chronic liver disease in Korea. This study investigated the seroprevalence of HBV infection with an emphasis on the coexistence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs). In all, 290,212 people undergoing health check-up examinations in 29 institutions during 2009 were recruited. The crude seroprevalences of HBsAg and anti-HBs was adjusted by age, sex, and geographic area using the 2009 estimated population of Korea. The adjusted seroprevalences of HBsAg and anti-HBs was 4.0% and 73.5%, respectively. Males showed higher HBsAg positivity and lower anti-HBs positivity than females ( P < 0.001). HBsAg positivity increased with age from 3.5% in people 20-29 years old to 4.8% in people 40-49 years old, followed by a decrease in people ≥50 years old. HBsAg positivity in Southern provinces (4.5%) including Jeju (5.9%), was significantly higher than that in Central provinces (3.6%; P < 0.001). Interestingly, HBsAg and anti-HBs coexisted in 0.1% of the total subjects and in 2.9% of the HBsAg-positive group, showing distinct age distribution and higher alanine aminotransferase levels than those of the group positive for only HBsAg. In conclusion, the seroprevalence of HBsAg and anti-HBs in Korea varies significantly by age, sex and geographical location and coexisted in 2.9% of HBsAg-positive subjects. Continuous monitoring of seroepidemiology may facilitate the eventual eradication of HBV infection. J. Med. Virol. 85:1327-1333, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Sorafenib is an orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma ( HCC). However, clinical parameters that may predict the treatment outcomes in sorafenib-treated advanced HCC patients remains unknown. Methods A total of 99 advanced ( BCLC C) HCC patients treated with sorafenib as an initial treatment modality from January 2007 to December 2011 were retrospectively reviewed. Overall survival was the primary endpoint for the analysis. Various clinical parameters including tumour stage and adverse effects to sorafenib were analysed. Univariate and multivariate analysis were carried out to identify clinical parameters predictive of the effect of sorafenib. Results There were 86 males and 13 females included in this study, with a median age of 53 years. The median overall survival was 91 days. Sixty-nine patients had Child-Pugh class A cirrhosis and 30 patients had Child-Pugh class B cirrhosis. Hepatitis B virus was the predominant cause of HCC (75.8%). Noted adverse effects were hand-foot syndrome, diarrhoea, fatigue, abdominal pain, nausea and stomatitis. The presence of hand-foot syndrome and diarrhoea and the absence of portal vein thrombosis and lymph node metastasis predicted a better overall survival in the multivariate analysis. Excluding the absence of lymph node metastasis, the same parameters were associated with a longer radiological time to progression. Conclusion Advanced HCC patients treated with sorafenib who experienced hand-foot syndrome and diarrhoea showed better overall survival than patients without these side effects. These side effects may be used as clinical parameters predictive of sorafenib response in patients with HCC. [ABSTRACT FROM AUTHOR]

Background/Aims Acute hepatic failure ( AHF) is one of the most serious complications of transcatheter arterial chemoembolization ( TACE). The aims of this study were to investigate risk factors of AHF after TACE and to establish a predictive model for AHF. Methods In the evaluation set, a total of 820 patients who underwent TACE as a first treatment for hepatocellular carcinoma were included. The demographic, laboratory, radiological and treatment-related factors were analysed to identify risk factors for AHF after TACE and a predictive model was established using the identified risk factors. In the validation set, a different cohort of 438 patients was included to validate the predictive model. Results The incidence of post- TACE AHF was 15.1% (124/820). Multivariate analysis revealed that presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and log alpha-foetoprotein levels, and low albumin and sodium levels were independent risk factors. A mathematical model was established using these independent risk factors, and the area under the receiver operating characteristic curve of the model was 0.773 (95% confidence interval, 0.726-0.820). The cut-off value of 9 had a sensitivity of 78.2%, a specificity of 72.3%, a positive likelihood ratio of 2.82, a negative likelihood ratio of 0.30, a positive predictive value of 28.9% and a negative predictive value of 95.8%. Conclusions The risk factors of post- TACE AHF were presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and alpha-foetoprotein levels, and low serum albumin and sodium levels. A mathematical model to predict post- TACE AHF was established. [ABSTRACT FROM AUTHOR]

Background and Aim: Adefovir add-on therapy is recommended for patients infected with lamivudine-resistant hepatitis B virus (HBV). We aimed to describe the long-term treatment outcome and predictors for good response of adefovir add-on therapy. Methods: A total of 559 chronic hepatitis B (CHB) patients who had been treated for at least 12 months with adefovir add-on therapy due to resistance to lamivudine were retrospectively included. Complete virologic response (CVR) was defined as serum HBV DNA < 9 IU/mL. Viral responses at 6 months were classified as PCR negativity, partial virologic response (PVR, HBV DNA < 2000 IU/mL), or inadequate virologic response (IVR, HBV DNA ≥ 2000 IU/mL). Results: The median duration of follow-up was 31.5 months (range, 12-56). The cumulative probabilities of CVR during adefovir add-on therapy were 58%, 70%, 78%, and 80% at 12, 24, 36, and 43 months, respectively. The cumulative rates of resistance to adefovir were 0.4%, 0.8%, and 3.1% at 12, 24, and 36 months, respectively. The only baseline factor associated with CVR (hazard ratio 0.83, 95% confidence interval 0.62-0.91, P ≤ 0.001) and resistance to adefovir (hazard ratio 1.925, 95% confidence interval 1.13-3.30, P = 0.017) was serum HBV DNA level. Comparison of the cumulative rates of CVR and resistance to adefovir according to viral response at 6 months showed significant differences among the three groups ( P < 0.0001 and P = 0.0005, respectively). Conclusions: Pre-treatment HBV DNA level and viral response at 6 months is associated with treatment outcome for adefovir-add on therapy in lamivudine resistance. [ABSTRACT FROM AUTHOR]

Background/Aims Serum alanine aminotransferase ( ALT) is an easily available, low-cost screening tool for detecting silent chronic liver disease. Recent studies have suggested that the currently accepted healthy ALT thresholds be lowered. Methods In this retrospective cross-sectional study, we determined upper thresholds for ALT values in a nationally representative healthy cohort ( n = 3337) from the Fourth Korea National Health and Nutrition Examination Survey ( KNHANES IV). Sensitivity and specificity of the currently used ALT threshold (40 IU/L, regardless of gender) was compared against study-derived, gender-specific ALT thresholds for detecting individuals at risk for chronic liver disease in 27 913 health check-up participants. Results The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free KNHANES participants were 34 IU/L for men and 25 IU/L for women. The prevalence of ALT elevation among health check-up participants was 11.0% in currently used thresholds, and increased to 22.6% with study-derived, gender-specific thresholds. Of the population who were additionally defined to have elevated ALT levels under new ALT threshold, 65.7% were at risk for chronic liver disease. Sensitivity for detecting individuals at risk for chronic liver disease improved from 18 to 33% with new thresholds whereas a trade-off in specificity (from 96 to 88%) was observed. Conclusions It is recommendable to lower the current ALT thresholds to better identify individuals at risk for chronic liver disease. [ABSTRACT FROM AUTHOR]

Background and Aim: There are insufficient data on renal safety during long-term adefovir dipivoxil (ADV) treatment. We aimed to elucidate the incidence and risk factors of renal impairment in chronic hepatitis B (CHB) patients treated with ADV. Methods: We retrospectively enrolled 687 CHB patients (51.4% with compensated cirrhosis) treated with ADV alone (18.2%) or in combination with lamivudine (81.8%) for more than 12 months. Renal function was measured using the estimated glomerular filtration rate (eGFR), and renal dysfunction was defined as mild (20-30% decrease), moderate (30-50%), or severe (more than 50%). Results: During the median treatment duration of 27 months, 72 patients (10.5%) developed renal impairment, which was mild in 77.8% of cases, moderate in 20.8% of cases, and severe in one patient. The cumulative incidence of renal impairment at 1, 3, and 5 years was 2.6%, 14.8%, and 34.7%, respectively. Modification of the dosing interval or discontinuation of ADV was required in seven and three patients, respectively, and none of them showed a further decline in the eGFR. Although a univariate analysis revealed age, the number of exposure to radio-contrast dye, liver cirrhosis, and hepatocellular carcinoma as risk factors of renal impairment, age was the only significant risk factor identified in the multivariate analysis (odds ratio = 1.048, 95% confidence interval = 1.019-1.076, P = 0.001). Conclusions: Renal impairment in long-term ADV users was relatively frequent, but serious renal toxicity was rare, and all cases were safely managed. Careful monitoring of renal function is required, especially in older patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Serum ferritin has been suggested as a potential biomarker associated with disease progression in metabolic dysfunction–associated steatotic liver disease (MASLD).We investigated the association between serum ferritin levels and liver‐related events (LREs) in individuals with steatotic liver disease (SLD).This cohort study included 17,560 adults with SLD (MASLD [n = 15,744], MASLD with increased alcohol intake (MetALD) [n = 1103] and cryptogenic SLD [n = 713]) without LRE at baseline. A steatotic liver was diagnosed using ultrasound, and LRE was defined as the development of decompensation (ascites, variceal bleeding and hepatic encephalopathy) or hepatocellular carcinoma. Participants were categorised into high (≥ 300 μg/L for males, ≥ 200 μg/L for females) or normal to low (< 300 μg/L for males, < 200 μg/L for females) ferritin levels.During 211,425 person‐years of follow‐up (median: 12.3 years), 74 incident LRE cases were identified, with 63 cases in MASLD, 10 in MetALD and 1 in cryptogenic SLD. The multivariable‐adjusted hazard ratio (aHR) for LRE comparing individuals with high and normal‐to‐low ferritin level was 3.13 (95% confidence interval [CI] 1.89–5.18). Increased risk of LRE in individuals with high serum ferritin level compared to those with normal to low serum ferritin level was consistent across SLD subtypes (aHR 2.69, 95% CI 1.55–4.67 for MASLD; aHR 5.73, 95% CI 1.31–25.0 for MetALD), and SLD severity assessed by Fibrosis‐4 (FIB‐4) index (aHR 2.38, 95% CI 1.34–4.21 for FIB‐4 ≥ 1.3; aHR 3.13, 95% CI 1.18–8.29 for FIB‐4 < 1.3).Serum ferritin levels correlated with the risk of LRE in patients with SLD. [ABSTRACT FROM AUTHOR]

Background/aims: As the core gene of hepatitis B virus (HBV) is a major immunological target, its mutation may evoke or evade immune clearance. We investigated the frequency and location of HBV core gene substitutions according to hepatitis B e antigen (HBeAg) status and viral replication status, and evaluated the association of these substitutions with the different stages of chronic HBV infection in Korean patients., Methods: The study population included 45 HBeAg-positive/DNA-positive patients (group I), 49 HBeAg-negative/DNA-positive patients (II) and 50 HBeAg-negative/DNA-negative patients (III). The HBV core gene was analysed by polymerase chain reaction (PCR) and sequencing., Results: The frequency of core gene substitutions increased from group I to group III. Substitutions were commonly detected at codons 87, 97, 112 and 130. The frequency of substitutions at codons 87 and 112 was higher in groups II/III than in group I. The frequency of the codon I97F substitutions was the highest in group III. However, the codon 130 substitution was more frequently found in groups I/II than in group III., Conclusion: Core gene substitutions were more frequently detected in HBeAg-negative and/or HBV DNA-negative patients. The substitutional hot spots were codons 87, 97, 112 and 130; substitutions at these codons might play a role in immune-modulation during the course of chronic HBV infection.