High-dose proton pump inhibitor treatment is associated with a higher mortality in cirrhotic patients: A multicentre study.

BACKGROUND: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. AIMS: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. METHODS: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome. RESULTS: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001). CONCLUSIONS: The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease.

OBJECTIVE: We explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease (CVD) risk. DESIGN: From nationwide health screening data, we identified 9 775 066 adults aged 20-79 who underwent health examination in 2009. Participants were categorised into four mutually exclusive groups: (1) MASLD; (2) MASLD with increased alcohol intake (MetALD); (3) MASLD with other combined aetiology (the three collectively referred to as MASLD/related steatotic liver disease (SLD)); and (4) no MASLD/related SLD. SLD was determined by fatty liver index ≥30. The primary outcome was CVD event, defined as a composite of myocardial infarction, ischaemic stroke, heart failure or cardiovascular death. RESULTS: The prevalence of MASLD, MetALD and MASLD with other combined aetiology was 27.5%, 4.4% and 1.5%, respectively. A total of 8 808 494 participants without prior CVD were followed up for a median of 12.3 years, during which 272 863 CVD events occurred. The cumulative incidence and multivariable-adjusted risk of CVD were higher in participants with MASLD/related SLD than in those without (HR 1.38 (95% CI 1.37 to 1.39)). Multivariable-adjusted HR (95% CI) of CVD events was 1.39 (1.38 to 1.40) for MASLD, 1.28 (1.26 to 1.30) for MetALD and 1.30 (1.26 to 1.34) for MASLD with other combined aetiology compared to the absence of any of these conditions. CVD risk was also higher in participants with metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease than in those without the respective condition. CONCLUSION: Over one-third of Korean adults have MASLD/related SLD and bear a high CVD risk.

Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma.

BACKGROUNDS: It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS: This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS: A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS: Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.

Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study.

BACKGROUND: Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. AIMS: To assess the treatment and renal/bone safety outcomes following the switch to TAF. METHODS: We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF. RESULTS: We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). CONCLUSIONS: At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

Impact of Low Skeletal Muscle Mass on Long-Term Outcomes in Hepatocellular Carcinoma Treated with Trans-Arterial Radioembolization: A Retrospective Multi-Center Study.

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90-loaded microspheres. This was a multi-center retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT), and 126 (36.3%) were classified as LSMM. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7), and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that LSMM (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p < 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p < 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment LSMM independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.

TM4SF5-mediated abnormal food-intake behavior and apelin expression facilitate non-alcoholic fatty liver disease features.

Transmembrane 4 L six family member 5 (TM4SF5) engages in non-alcoholic steatohepatitis (NASH), although its mechanistic roles are unclear. Genetically engineered Tm4sf5 mice fed ad libitum normal chow or high-fat diet for either an entire day or a daytime-feeding (DF) pattern were analyzed for metabolic parameters. Compared to wild-type and Tm4sf5-/- knockout mice, hepatocyte-specific TM4SF5-overexpressing Alb-TGTm4sf5-Flag (TG) mice showed abnormal food-intake behavior during the mouse-inactive daytime, increased apelin expression, increased food intake, and higher levels of NASH features. DF or exogenous apelin injection of TG mice caused severe hepatic pathology. TM4SF5-mediated abnormal food intake was correlated with peroxisomal ß-oxidation, mTOR activation, and autophagy inhibition, with triggering NASH phenotypes. Non-alcoholic fatty liver disease (NAFLD) patients' samples revealed a correlation between serum apelin and NAFLD activity score. Altogether, these observations suggest that hepatic TM4SF5 may cause abnormal food-intake behaviors to trigger steatohepatitic features via the regulation of peroxisomal ß-oxidation, mTOR, and autophagy.

The efficacy of treatment for hepatocellular carcinoma in elderly patients.

BACKGROUND/AIM: Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. METHODS: Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. RESULTS: Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P<0.001). In early-stage HCC, surgery yielded significantly lower OS in elderly patients compared to non-elderly patients (median, 97.4 vs. 138.0 months; P<0.001), however, local ablation (median, 82.2 vs. 105.5 months) and transarterial therapy (median, 42.6 vs. 56.9 months) each provided comparable OS between the two groups after inverse probability of treatment weighting (IPTW) analysis (all P>0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). CONCLUSIONS: Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.

Effect of 12-week intermittent calorie restriction compared to standard of care in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD can result in various complications. Owing to the lack of effective pharmacological therapies, lifestyle modifications are the cornerstone treatment for NAFLD. However, there has been no recommendation for a specific dietary therapy. Because no significant effects have been observed in previous studies. Intermittent calorie restriction (ICR) consists of alternating phases of extreme energy restriction and regular energy intake. Recent studies have demonstrated a significantly higher reduction in liver fat content in the ICR group than in the standard of care (SOC) or continuous calorie restriction groups in patients with NAFLD. However, critical weaknesses limit the broader application of ICR in clinical practice; those are a lack of appropriate assessment tools, different cutoffs of body mass index (BMI) used to define obesity, and different food portions. Thus, we report a protocol for a prospective, randomized controlled trial. The trial will evaluate the effect of 12-week ICR on improving liver fat content in NAFLD patients (Nonalcoholic Fatty Liver Disease-Intermittent Calorie Restriction [FLICR]). METHODS: We will include adult (19-75 years) NAFLD patients. NAFLD will be diagnosed by histologic assessment or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 8%. A total of 72 patients will be classified according to BMI (obese group: BMI ≥ 25 kg/m2 [n = 36] and non-obese group: BMI < 25 kg/m2 [n = 36]). Participants will be followed up for 24 weeks. Participants will be randomly assigned to one of the two groups: the SOC or ICR group. The primary objective will be the change in liver fat content measured using MRI-PDFF from baseline to 12 weeks. DISCUSSION: This FLICR study may provide clinical evidence on ICR in the treatment of NAFLD in both obese and non-obese patients. The use of ICR in patients with NAFLD will improve the clinical outcomes of patients facing a shortage of effective medical therapy. TRIAL REGISTRATION: This trial was registered at the United States National Library of Medicine (NLM) at the National Institutes of Health. CLINICALTRIALS: gov NCT05309642. Registered on April 4, 2022.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 Expert consensus-based practical recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Transarterial Chemoembolization for Hepatocellular Carcinoma: 2023 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post-procedural patient care.

Therapeutic Mechanisms and Clinical Effects of Glucagon-like Peptide 1 Receptor Agonists in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) can lead to liver fibrosis and cirrhosis. Recently, glucagon-like peptide 1 receptor agonists (GLP-1RAs), a class of drugs used to treat type 2 diabetes and obesity, have shown therapeutic effects against NAFLD. In addition to reducing blood glucose levels and body weight, GLP-1RAs are effective in improving the clinical, biochemical, and histological markers of hepatic steatosis, inflammation, and fibrosis in patients with NAFLD. Additionally, GLP-1RAs have a good safety profile with minor side effects, such as nausea and vomiting. Overall, GLP-1RAs show promise as a potential treatment for NAFLD, and further studies are required to determine their long-term safety and efficacy.

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study.

Background/Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. Methods: This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. Results: In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. Conclusions: This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Inverse Propensity Score-Weighted Analysis of Entecavir and Tenofovir Disoproxil Fumarate in Patients with Chronic Hepatitis B: A Large-Scale Multicenter Study.

Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) in preventing hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients; however, it remains controversial. This study aimed to conduct comprehensive comparisons between the two antivirals. CHB patients initially treated with ETV or TDF between 2012 and 2015 at 20 referral centers in Korea were included. The primary outcome was the cumulative incidence of HCC. The secondary outcomes included death or liver transplantation, liver-related outcome, extrahepatic malignancy, development of cirrhosis, decompensation events, complete virologic response (CVR), seroconversion rate, and safety. Baseline characteristics were balanced using the inverse probability of treatment weighting (IPTW). Overall, 4210 patients were enrolled: 1019 received ETV and 3191 received TDF. During the median follow-ups of 5.6 and 5.5 years, 86 and 232 cases of HCC were confirmed in the ETV and TDF groups, respectively. There was no difference in HCC incidence between the groups both before (p = 0.36) and after IPTW was applied (p = 0.81). Although the incidence of extrahepatic malignancy was significantly higher in the ETV group than in the TDF group before weighting (p = 0.02), no difference was confirmed after IPTW (p = 0.29). The cumulative incidence rates of death or liver transplantation, liver-related outcome, new cirrhosis development, and decompensation events were also comparable in the crude population (p = 0.24-0.91) and in the IPTW-adjusted population (p = 0.39-0.80). Both groups exhibited similar rates of CVR (ETV vs. TDF: 95.1% vs. 95.8%, p = 0.38), and negative conversion of hepatitis B e antigen (41.6% vs. 37.2%, p = 0.09) or surface antigen (2.8% vs. 1.9%, p = 0.10). Compared to the ETV group, more patients in the TDF group changed initial antivirals due to side effects, including decreased kidney function (n = 17), hypophosphatemia (n = 20), and osteoporosis (n = 18). In this large-scale multicenter study, ETV and TDF demonstrated comparable effectiveness across a broad range of outcomes in patients with treatment-naïve CHB during similar follow-up periods.

Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis.

BACKGROUND/AIMS: Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. METHODS: This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). RESULTS: In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28-0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0-56.7%, whereas that of the TKI group was 12.3-15.0%. CONCLUSION: For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.

CAGE-B and SAGE-B models better predict the hepatitis B virus-related hepatocellular carcinoma after 5-year entecavir treatment than PAGE-B.

OBJECTIVES: The PAGE-B model consists of variables at the initiation of antiviral therapy (AVT), whereas the SAGE-B and CAGE-B models consist of variables after 5 years of AVT. We aimed to compare the predictive accuracy of three risk prediction models for hepatocellular carcinoma (HCC) development after 5 years of AVT in patients with chronic hepatitis B (CHB). METHODS: A total of 1335 patients who initiated entecavir (ETV) treatment between 2006 and 2011 and were followed up for more than 5 years were enrolled in the study. RESULTS: At ETV initiation, the median age was 49 years and the median score of the PAGE-B model was 14. After 5 years of ETV treatment, the median SAGE-B and CAGE-B scores were 6 and 6. During the study period, 93 (7.0%) patients developed HCC after 5-year treatment. In multivariate analysis, PAGE-B (hazard ratio [HR] 1.151, 95% confidence interval [CI] 1.087-1.219), SAGE-B (HR 1.340, 95% CI 1.228-1.463), and CAGE-B (HR 1.327, 95% CI 1.223-1.440) models independently predicted HCC development after 5 years of treatment (all P < 0.001). The high-risk groups of the three risk prediction models showed a significantly higher risk of HCC development compared to the medium- and low-risk groups (both P < 0.05). The AUROC of the SAGE-B (0.772-0.844) and CAGE-B (0.785-0.838) models was significantly higher than those of the PAGE-B model (0.696-0.745) in predicting HCC development after 5 years of treatment (both P < 0.05). CONCLUSION: The SAGE-B and CAGE-B models might be better than the PAGE-B model in predicting HCC development after 5 years of ETV treatment.

Personalized Antiviral Drug Selection in Patients With Chronic Hepatitis B Using a Machine Learning Model: A Multinational Study.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.