Hepatitis B relapse after entecavir or tenofovir alafenamide cessation under anti-viral prophylaxis for cancer chemotherapy.

BACKGROUND: No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). METHODS: A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. RESULTS: The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment. CONCLUSIONS: In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma.

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Weight Gain and Increased Body Mass Index in Patients with Hepatitis C after Eradication Using Direct-Acting Antiviral Therapy in Taiwan.

Few studies have reported weight gain in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral agents (DAAs). This retrospective cohort study identified factors associated with substantial weight gain after DAA treatment in Taiwan. This study involved patients treated using DAAs at the Chiayi and Yunlin branches of Chang Gung Memorial Hospital from 1 January 2017 to 31 October 2020. Body weight data were collected at the start of DAA therapy and 2 years after the confirmation of a sustained virologic response. We performed multiple logistic regression to evaluate the clinical and laboratory parameters associated with a large body mass index (BMI) increase (≥5%). The mean BMI was 25.56 ± 4.07 kg/m2 at baseline and 25.77 ± 4.29 kg/m2 at the endpoint (p = 0.005). A considerable reduction in fibrosis-4 (FIB-4) score was a significant predictor of a large BMI increase (OR: 1.168; 95% CI: 1.047-1.304, p = 0.006). By contrast, older age (OR: 0.979; 95% CI: 0.963-0.996, p = 0.013) and a higher baseline BMI (OR: 0.907; 95% CI: 0.863-0.954, p < 0.001) were associated with a reduced risk of a large increase in BMI at the endpoint. In summary, a larger BMI increase was closely associated with a younger age, lower baseline BMI, and higher FIB-4 score reduction. Notably, differences in DAA regimens did not affect outcomes. Future studies are needed to elucidate the long-term effects and metabolic outcomes associated with this body weight change and investigate the exact underlying mechanisms.

Well-controlled viremia reduces the progression of hepatocellular carcinoma in chronic viral hepatitis patients treated with lenvatinib.

Lenvatinib has been approved as one of the first-line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non-inferior to sorafenib. Previous studies have shown well-controlled viremia contributes to the prognosis of HCC patients receiving first-line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first-line lenvatinib treatment in our institute were assessed. High-effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct-acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV-related HCC (HBV-HCC) and 44 patients with HCV-related HCC (HCV-HCC), respectively. Progression-free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV-HCC patients and 88.4% of the HCV-HCC patients had well-controlled viremia, and their PFS (8.8 vs. 3.1 months, p < 0.001) and OS (30.2 vs. 12.8 months, p = 0.041) were better than those who had uncontrolled viremia; moreover, well-controlled viremia reduced tumor progression in multivariate analysis (Hazard ratio: 0.41, 95% confidence interval: 0.25-0.68, p = 0.001) after adjusting for albumin-bilirubin grade and concurrent treatment. HBV or HCV infection was not associated with tumor progression of HCC patients receiving lenvatinib, but viremia, controlled or not, was.

Survival Evidence of Local Control for Colorectal Cancer Liver Metastases by Hepatectomy and/or Radiofrequency Ablation.

Hepatectomy and/or local ablation therapy have been recommended for colorectal cancer liver metastases (CRLM). However, they still lack strong evidence for their survival benefits, in addition to systemic therapy. This study aims to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in CRLM patients from a large multi-institutional database. A total of 20,251 patients with colorectal cancer, 4521 of whom were with CRLM, were screened for eligibility. Finally, 2612 patients (637 hepatectomy, 93 RFA, 92 combined hepatectomy and RFA, and 1790 non-aggressive treatment) were enrolled. Frequency matching analysis was used to adjust for baseline differences. The 5-year overall survival (OS) was as follows: hepatectomy alone was 47.8%, combined hepatectomy plus RFA was 35.9%, RFA alone was 29.2%, and the non-aggressive treatment group was 7.4%. Kaplan-Meier curves showed that hepatectomy, RFA, and combination were significantly associated with a better OS compared to those without aggressive local therapy (p < 0.001). Multivariate Cox regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.81-0.97; p = 0.011), old age (≥60 years) (HR 1.20; 95% CI, 1.09-1.32; p < 0.001), high CEA level (>5 ng/mL) (HR 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right-sided cancer (HR 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR 0.7; 95% CI, 0.62-0.79; p < 0.001), and aggressive local therapy (hepatectomy vs. non-local therapy HR 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in a better OS than those without (p < 0.001). In conclusion, aggressive local treatment provides survival advantages over systemic therapy alone among CRLM patients.

Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma.

BACKGROUND: Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice. METHODS: We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). RESULTS: In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1-2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. CONCLUSION: The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice.

Higher rate of HBsAg loss after discontinuation of tenofovir than entecavir in patients with chronic hepatitis B.

BACKGROUND/AIMS: To compare the rates of hepatitis B surface antigen (HBsAg) loss after discontinuation of entecavir versus tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) without cirrhosis. METHODS: A total of 891 patients who received entecavir (n = 556) or TDF (n = 335) followed up post-treatment for at least 12 months were retrospectively assessed. A total of 677 patients who had continued entecavir or TDF therapy for at least 4 years were enrolled as the continued group. RESULTS: Patients who discontinued TDF had higher rates of virological and clinical relapse and retreatment than patients who discontinued entecavir in both the HBeAg-positive and HBeAg-negative subgroups. In the entire discontinued cohort, the cumulative rates of HBsAg loss at 7 years were 22.6% and 35.4% in the entecavir and TDF groups respectively. Patients who discontinued TDF had significantly higher rates of HBsAg loss than patients who discontinued entecavir therapy in all (p = 0.019) and propensity score-matched (p = 0.015) patients, especially among the subgroups who achieved a sustained response (p < 0.001). Cox regression analysis revealed that TDF, longer treatment duration and lower HBsAg levels at end of treatment were independently associated with HBsAg loss in the entire discontinued group. The incidence of HBsAg loss was significantly higher in the discontinued group than in the continued group after propensity score matching (p < 0.001), including HBeAg-positive and HBeAg-negative patients. CONCLUSIONS: Patients who discontinued TDF had significantly higher rates of HBsAg loss than patients who discontinued entecavir, especially among the subgroups without HBV relapse after cessation of therapy.

Nomogram to Predict the Long-Term Overall Survival of Early-Stage Hepatocellular Carcinoma after Radiofrequency Ablation.

Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.

The Efficacy and Safety of Ramucirumab in Heavily Pretreated Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: Ramucirumab has been approved for the management of hepatocellular carcinoma (HCC) after progression on sorafenib; however, the data on ramucirumab in heavily pretreated HCC are limited. This study aimed to investigate the real-world efficacy and safety of ramucirumab in patients with heavily pretreated advanced HCC. PATIENTS AND METHODS: Patients with advanced HCC who received intravenous ramucirumab as second-line and later therapy were retrospectively reviewed. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Additionally, prognostic factors were estimated using hazard ratios with 95% confidence intervals. RESULTS: In total, 31 patients with advanced HCC who received ramucirumab were enrolled, including 11 patients with second-line treatment and 20 with third-line and later-line treatment. The objective response rate was 3.2% with a disease control rate (DCR) of 45.2%, and the DCR of ramucirumab between the second-line group and the third-line and later-line groups did not differ. The median PFS and OS were 2.1 months and 6.7 months, respectively, in the whole population. In the multivariate analyses, alpha-fetoprotein <1,000 ng/ml was an independent prognostic factor for better PFS and OS. All adverse events were classified as grade 1-2 without grade 3-4 toxicities or drug-related mortality. Additionally, 51.6% of patients received subsequent therapy after progression on ramucirumab. CONCLUSION: The results of our study show the efficacy and safety of ramucirumab in patients with heavily pretreated HCC in real-world practice.

Usefulness of controlled attenuation parameter in monitoring clinically relevant decline of hepatic steatosis for non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is the reference standard of hepatic steatosis assessment. This study evaluates usefulness of controlled attenuation parameter (CAP) in monitoring the clinically relevant outcome by MRI-PDFF for non-alcoholic fatty liver disease (NAFLD) patients. METHODS: NAFLD patients were enrolled prospectively. Instruction was given in lifestyle modifications with exercise and control of metabolic factors. MRI-PDFF and CAP were performed at enrollment and follow-up, with the diagnostic validity of CAP in monitoring clinically relevant outcome defined as a decline of ≥30% relative to baseline value by MRI-PDFF. RESULTS: A total of 75 patients (male/female: 49/26, mean age: 53.2) were enrolled. Baseline MRI-PDFF, CAP and liver stiffness was 14.4%, 300.2 dB/m and 6.5 kPa. In a median interval of 369 days, thirteen (17.3%) patients achieved clinically relevant outcome with decline of 46.7 dB/m by CAP, compared with increase of 5.1 in the other patients. In multivariate analysis, clinically relevant outcome was associated with changes (Δ) of CAP and glucose. Assessed by area under receiver operating curve, the performances of ΔCAP in predicting clinically relevant outcome were 0.815 and 0.808, and with the specificity of >90%, the ΔCAP cutoff was -46 dB/m and -15% relative to baseline value; sensitivity was 53.8% and 46.2% with negative predictive value of 90.3% and 88.9% respectively. CONCLUSIONS: For NAFLD patients, CAP exhibited good performance in monitoring clinically relevant decline of hepatic steatosis in MRI-PDFF. With the cutoffs of -46 dB/m or -15%, ΔCAP is useful in excluding clinical relevant outcome achievement.

Living donor liver transplantation for Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma.

Background: Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) hepatocellular carcinoma (HCC) is highly heterogeneous; thus, identifying the most effective treatment for individual patients represents a significant clinical challenge. However, transarterial chemoembolization (TACE) is the only recommended treatment option. Therefore, we aimed to investigate the patient characteristics and outcomes of living donor liver transplantation (LDLT) for BCLC stage B HCC. Methods: A total of 516 patients with BCLC stage B HCC who underwent LDLT (n=104) or did not undergo LDLT (non-LDLT; n=412) between 2004 to 2018 were analyzed by propensity score matching (PSM; 1:4) analysis. Factors influencing overall survival (OS) and recurrence were analyzed using Cox's proportional hazards models. Results: Patients treated with LDLT achieved better OS than the non-LDLT group, including liver- and non-liver related survival (all P<0.001). Multivariate Cox regression analysis showed age >60 years (P=0.006), a neutrophil-lymphocyte ratio (NLR) >4 (P=0.016) and >3 locoregional therapies (LRT) before LDLT (P<0.001) were independent risk factors for HCC recurrence. In addition, age >60 years (P<0.001) and >3 LRT before LDLT (P=0.001) were independent risk factors for OS. Using a combination of age, NLR, and LRT before liver transplantation (LT), the patients can be divided into low-risk (none of risk), intermediate-risk (one of risk), and high risk (more than two of risk) groups. There were significant differences in the cumulative HCC recurrence (P<0.001) and mortality (P<0.001) rates among the three groups. Conclusions: LDLT may represent a valuable therapeutic option for selected patients with BCLC stage B HCC.

Prediction model of hepatocellular carcinoma in patients with hepatitis B virus-related compensated cirrhosis receiving antiviral therapy.

The feasibility and performance of predicting hepatocellular carcinoma (HCC) using a combined albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4)-based model remain unclear in patients with compensated cirrhosis and chronic hepatitis B (CHB) receiving long-term nucleos(t)ide analog (NA) therapy. We enrolled 1158 NA-naïve patients with compensated cirrhosis and CHB treated with entecavir or tenofovir disoproxil fumarate. The patients' baseline characteristics, hepatic reserve, and fibrosis indices were analyzed. The combination of ALBI and FIB-4 was used to develop a prediction model of HCC. In this cohort, the cumulative incidence rates of HCC at 3, 5, and 10 years were 8.1%, 13.2%, and 24.1%, respectively. The combination of ALBI and FIB-4, Diabetes mellitus, and Alpha-fetoprotein (AFDA) were independent risk factors for HCC. The combined ALBI and FIB-4-based prediction model (i.e., AFDA) stratified the cumulative risk of HCC into three groups (with risk scores of 0, 1-3, 4-6) among all patients (P < 0.001). AFDA exhibited the highest area under the receiver operating characteristic (0.6812) for predicting HCC, which was higher than those of aMAP (0.6591), mPAGE-B (0.6465), CAMD (0.6379), and THRI (0.6356) and significantly higher than those of PAGE-B (0.6246), AASL-HCC (0.6242), and HCC-RESCUE (0.6242). Patients with a total score of 0 (n = 187, 16.1% of total patients) had the lowest cumulative HCC incidence of 3.4% at 5 years. The combined ALBI and FIB-4-based prediction model can stratify the risk of HCC in patients with compensated cirrhosis and CHB receiving NA therapy.

Post-treatment HBsAg decline predicts high rate of HBsAg loss after stopping entecavir or tenofovir in HBeAg-negative patients without retreatment.

BACKGROUND/AIMS: Little is known about the role of post-treatment HBsAg decline in HBsAg loss following nucleos(t)ide analogues cessation. METHODS: HBeAg-negative patients without cirrhosis who previously received entecavir or tenofovir disoproxil fumarate (TDF) were enrolled (n=530). All patients were followed-up post-treatment for >24 months. RESULTS: Of the 530 patients, 126 achieved sustained response (Group I), 85 experienced virological relapse without clinical relapse and retreatment (Group II), 67 suffered clinical relapse without retreatment (Group III) and 252 received retreatment (Group IV). The cumulative incidence of HBsAg loss at 8 years was 57.3% in Group I, 24.1% in Group II, 35.9% in Group III and 7.3% in Group IV. Cox regression analysis showed that nucleos(t)ide analogue experience, lower HBsAg levels at end-of-treatment (EOT) and higher HBsAg decline at 6 months after EOT were independently associated with HBsAg loss in Group I and Groups II+III. The rates of HBsAg loss at 6 years in patients with HBsAg decline >0.2 log IU/mL in Group I and HBsAg decline >0.15 log IU/mL in Group II+III at 6 months after EOT were 87.7% and 47.1%, respectively. CONCLUSION: The HBsAg loss rate was high and post-treatment HBsAg decline could predict high HBsAg loss rate among HBeAg-negative patients who discontinued entecavir or TDF and did not need retreatment.

Effectiveness and safety of 8-week glecaprevir/pibrentasvir in HCV treatment-naïve patients with compensated cirrhosis: real-world experience from Taiwan nationwide HCV registry.

BACKGROUND: Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce. METHODS: The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated. RESULTS: Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related. CONCLUSIONS: In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.

Factors Associated with Large Renal Function Decline in Patients with Chronic Hepatitis C Successfully Treated with Direct-Acting Antiviral Therapy.

The findings regarding changes in renal function in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are controversial. This study attempted to identify the factors associated with the large decline in renal function following DAA treatment. This retrospective cohort study included patients treated with DAAs at Chiayi and Yunlin Chang Gung Hospitals, Taiwan, from 1 January 2017 to 31 October 2020. Estimated glomerular filtration rate (eGFR) data were collected within 90 days prior to DAA therapy and 2 years after the confirmation of a sustained virologic response (SVR). We performed multiple logistic regression to evaluate the clinical or laboratory parameters associated with a large eGFR decline (≥10%). Among the enrolled 606 patients, the mean eGFR at the baseline and endpoint were 84.11 ± 24.38 and 78.88 ± 26.30 mL/min/1.73 m2, respectively (p < 0.001). The factors associated with a large eGFR decline 2 years after the SVR included hypertension (OR: 1.481; 95% CI: 1.010-2.173, p = 0.044) and a higher baseline eGFR (OR: 1.016; 95% CI: 1.007-1.024, p < 0.001). A higher albumin level reduced the risk of a large eGFR decline (OR: 0.546; 95% CI: 0.342-0.872, p = 0.011). In the patients with HCV treated with DAAs, a larger renal function decline was more commonly observed in those with hypertension, a lower (but within normal range) albumin level, and a higher baseline eGFR, while DAA treatment had no effect. The clinical significance of these findings has to be further defined. Although some risk factors associated with chronic kidney disease may be alleviated after DAA treatment, the regular control and follow-up of risk factors and renal function are still recommended in at-risk patients after HCV eradication.

Short Half-Life of Des-γ-Carboxy Prothrombin Is a Superior Factor for Early Prediction of Outcomes of Hepatocellular Carcinoma Treated with Radiofrequency Ablation.

BACKGROUND: The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. MATERIALS AND METHODS: 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. RESULTS: Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). CONCLUSIONS: Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA.