V) Cirrhosis & HCC

66.9 years who visited National Taiwan University Hospital were prospectively recruited. Forty eight patients had cancer and 12 had benign strictures. Thirty four patients had cholangiocarcinoma, 3 had gallbladder cancer, 8 had hepatocellular carcinoma, 1 had ampullary cancer and 2 had metastatic cancer. Tissue sampling sensitivity varied according to the different sampling modalities; the highest yield was seen in forceps biopsy whenever before or after biliary dilation. The cumulative sensitivity of triple-tissue sampling in the cancer patients was as follows: sensitivity was 77.1% (before dilation) and 79.2% (after dilation) if atypia was considered malignant and 45.8% (before dilation) and 43.8% (after dilation) if atypia was considered benign. No serious complications occurred from the tissue sampling methods. Conclusions: Tissue sampling sensitivity varied according to the different sampling modalities. Triple tissue-sampling increased sensitivity; Dilation of biliary stricture has no influence on the diagnosis rate of tissue sampling.

Section：Cirrhosis & HCC ㉑

CONCURRENT IMMUNE CHECKPOINT INHIBITOR AND TYROSINE KINASE INHIBITOR THERAPY YIELDS BETTER OUTCOME THAN IMMUNE CHECKPOINT INHIBITOR MONOTHERAPY IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

Wei-Fan Hsu1,2,3, Hung-Wei Wang1,3 , Hsueh-Chou Lai1,4, Cheng-Kuo Chen5 , Po-Heng Chuang1, Ming-Hung Tsai6 , Wen-Pang Su1, Sheng-Hung Chen1,3 , Wen-Hsin Huang1, Chi-Ying Yang1 , Tsung-Yu Tsai1, Wang-De Hsiao1 , Chia-Sheng Chu1, Chun-Che Lin1,3 , Guan-Tarn Huang1,3, Jaw-Town Lin1,3 , Cheng-Yuan Peng1,3 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan2 School of Medicine, China Medical University, Taichung, Taiwan3 School of Chinese Medicine, China Medical University, Taichung, Taiwan4 Division of Gastroenterology & Hepatology, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan5 Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan6 併用免疫點抑制劑與酪氨酸激酶抑製 劑比單用免疫點抑制劑在晚期肝癌患 者提供更好療效

許偉帆1,2,3 王鴻偉1,3 賴學洲1,4 陳政國5 莊伯恒1 蔡明宏6 蘇文邦1 陳昇弘1,3 黃文信1 楊其穎1 蔡宗佑1 蕭望德1 朱家聲1 林俊哲1,3 黃冠棠1,3 林肇堂1,3 彭成元1,3 中國醫藥大學附設醫院消化醫學中心1 中國醫藥大學生物醫學研究所2 中國醫藥大學醫學系3 中國醫藥大學中醫學系4 亞洲大學附屬醫院肝膽胃腸科5

中國醫藥大學附設醫院血液腫瘤科6

Background: The treatment efficacy of immune checkpoint inhibitors (ICIs) with tyrosine kinase inhibitors (TKIs) for patients with advanced HCC is unknown. Aims: We investigated whether concurrent ICI and TKI therapy yielded better progression-free survival (PFS) and overall survival (OS) than did ICI monotherapy in patients with advanced HCC. Methods: This retrospective study enrolled 61 consecutive patients with advanced HCC from May 2017 to June 2021 at China Medical University Hospital and Asia University Hospital. Patients who received locoregional therapy during ICI therapy, including transarterial chemoembolization (n=14) or liver radiotherapy (n=21), were excluded. Patients who received concurrent ICI and TKI therapy for less than 7 days were also excluded. Results: Of the 61 patients, 38 (62.3%) patients received combination therapy. Nivolumab and pembrolizumab were used in 50 (82%) and 11 (18%) patients, respectively. The median ICI treatment duration was 2.47 (1.28–5.37) months (first quartile–third quartile). Of the 38 (62.3%) patients who received combination therapy with TKIs, 15, 16, 2, and 5 patients received sorafenib, lenvatinib, regorafenib, and sequential TKIs, respectively, and the median duration of combination treatment was 2.48 (0.98–5.98) months. Sixteen patients did not reach the time of first radiological imaging assessment at data analysis (14 patients died and 2 patients were lost to follow-up). Objective response (OR) and disease control rates were 21.3% and 36.1%, respectively. The median progression-free survival and overall survival was 2.40 (95% confidence interval [CI]: 2.22–2.58) and 5.87 (95% CI: 4.30–7.44) months, respectively. Alpha-fetoprotein (AFP) response, defined as ≥20% decline in serum AFP levels within the first 3 months of treatment, was the only factor associated with disease control (complete response + partial response + stable disease, odd ratio: 33.856, 95% CI: 5.188–220.941, p<0.001) by multivariate analysis. Patients with AFP response had lower alanine and aspartate aminotransferase levels, and lower Cancer of the Liver Italian Program score (2 (1–2) vs. 3 (2–4), p=0.027). Macrovascular invasion (MVI, hazard ratio [HR]: 3.045, 95% CI: 1.262–7.343, p=0.013), Child-Pugh class B (HR: 2.933, 95% CI: 1.332–6.457, p=0.008), concurrent TKI therapy (HR: 0.180, 95% CI: 0.075–0.433, p<0.001), and disease control (HR: 0.150, 95% CI: 0.051–0.443, p=0.001) were predictors of short PFS. Total tumor volume (>1000 cm3, HR: 2.683, 95% CI: 1.028–6.998, p=0.044), MVI (HR: 3.975, 95% CI: 1.347–11.731, p=0.012), ALBI grade 2 or 3 (HR: 4.467, 95% CI: 1.033–19.324, p=0.045), AFP response (HR: 0.281, 95% CI: 0.091–0.873, p=0.028), and concurrent TKI therapy (HR: 0.242, 95% CI: 0.093–0.632, p=0.004) were predictors of poor OS. Conclusions: Concurrent ICI and TKI therapy yielded better PFS and OS for patients with advanced HCC. AFP response was a predictor for disease control and longer OS.

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STRATIFICATION OF HEPATOCELLULAR CARCINOMA RISK THROUGH THE COMBINATION OF FIB-4 AND ALBI-BASED PREDICTION MODEL IN COMPENSATED CIRRHOTIC PATIENTS WITH CHRONIC HEPATITIS B RECEIVING NUCLEOS(T)IDE ANALOGUE THERAPY

Hung-Wei Wang1, Chien-Hung Chen2 , Hsueh-Chou Lai1, Chi-Yi Chen3 , Jing-Houng Wang2, Cheng-Yuan Peng1 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2 Division of Hepatogastroenterology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan3 FIB-4 與 ALBI 為主的預測模型可區分 慢性 B 型肝炎代償肝硬化患者接受類 核苷（酸）藥物治療後之肝癌發生風險

王鴻偉1 陳建宏2 賴學洲1 陳啟益3 王景弘2 彭成元1 中國醫藥大學附設醫院內科部消化醫學中心1 高雄長庚紀念醫院內科部胃腸肝膽科系2 嘉義基督教醫院內科部胃腸肝膽科3

Background: FIB-4 index is one of the noninvasive fibrosis indices widely used in patients with chronic hepatitis B (CHB). Albumin-bilirubin (ALBI) grade has been developed objectively to measure hepatic reserve and also utilized to predict liver related events, including hepatocellular carcinoma (HCC). The performance of predicting HCC through the combination of FIB-4 and ALBI-based model remains unclear. Aims: We investigated the predictive performance of HCC risk through liver reserve or noninvasive fibrosis markers derived from baseline parameters in compensated cirrhotic patients with CHB receiving nucleos(t)ide analogue (NA) therapy. Methods: We enrolled 1158 NA-naïve, compensated cirrhotic patients with CHB treated with entecavir or tenofovir from 2008 to 2018. Baseline patient characteristics and pre-treatment liver reserve and fibrosis indices were collected and analyzed to predict HCC risk by univariate and multivariate Cox regression analyses. The predictive performance was evaluated using receiver operating characteristic (ROC) curves. We used Kaplan–Meier analysis to compare the cumulative HCC incidence among three subgroups of patients exhibiting distinct combinations of FIB4 and ALBI. The combination of FIB-4 and ALBI was used to estimate regression coefficient in the multivariate Cox regression model, which was converted to risk score to develop the prediction model. Results: In this cohort, 161 patients (13.9%) developed HCC during a median follow-up period of 4.6 years. The cumulative incidences of HCC at 3, 5 and 10 years were 8.1%, 13.2% and 24.1%, respectively. By multivariate Cox regression analysis, diabetes mellitus (DM) (yes vs no) (hazard ratio [HR]: 1.469; 95% confidence interval [CI]: 1.035–2.058; P = 0.031), AFP (> 5.28 vs ≤ 5.28 ng/mL) (HR: 1.904; 95% CI: 1.298–2.794; P = 0.001), FIB-4 (> 2.54 vs ≤ 2.54) (HR: 1.746; 95% CI: 1.212–2.515; P = 0.003), and ALBI (> -2.66 vs ≤ -2.66) (HR: 1.575; 95% CI: 1.132–2.191; P = 0.007) were significant predictors of HCC. A combination of FIB-4 and ALBI stratified the cumulative risk of HCC into three subgroups in all patients (logrank test: P < 0.001) (high [n=340]: FIB-4 > 2.54/ ALBI > -2.66 [HR: 2.862, 95% CI: 1.833–4.469, P < 0.001]; intermediate [n=411]: FIB-4 > 2.54/ALBI ≤ -2.66 or FIB-4 ≤ 2.54/ALBI > -2.66 [HR: 1.927, 95% CI: 1.218–3.049, P = 0.005]; low [n=407]: FIB4 ≤ 2.54/ALBI ≤ -2.66 [HR: 1 as reference]). The combination of FIB-4 and ALBI-based prediction model (risk score 0–6) exhibited the highest predictive performance for HCC (AUROC = 0.683) compared to other scores (FIB-4, modified FIB-4, APRI, PAGE-B, ALBI, PALBI, and MELD, all P < 0.05) and stratified the cumulative risk of HCC into three subgroups in all patients (log-rank test: P < 0.001) (high [n=315]: score 5–6 [HR: 4.231, 95% CI: 2.795–6.406, P < 0.001]; intermediate [n=336]: score 3–4 [HR: 2.478, 95% CI: 1.583–3.880, P <

0.001]; low [n=507]: 0–2 [HR: 1 as reference]). According to this model, the 5-year cumulative incidence rates of HCC were 23.7% in patients with high risk (score 5–6), 13.8% in those with intermediate risk (score 3–4), and 5.7% in those with low risk (score 0–2). Conclusions: The combination of FIB-4 and ALBI-based prediction model could stratify the risk of HCC in compensated cirrhotic patients with CHB receiving NA therapy.

㉓

THE EFFECTIVENESS OF HEPATIC ARTERIAL INFUSION CHEMOTHERAPY (HAIC) FOLLOWED BY LIPIODOL INFUSION IN ADVANCED HEPATOCELLULAR CARCINOMA (HCC) WITH PORTAL VEIN TUMOR THROMBUS (PVTT)

Kun-Feng Tsai, Sheng-Yeh Tang, Ping-I Hsu Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan 肝動脈化學治療於嚴重侵犯性肝癌之 療效

蔡坤峰 湯昇曄 許秉毅 臺南市立安南醫院內科部 Background: The patients with advanced hepatocellular carcinoma with portal vein thrombosis have poor prognosis. The effectiveness of HAIC with follow up lipiodol infusion is uncertained. Aims: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. Responses were evaluated after two HAIC cycles and after completing HAIC. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated. Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the nonresponder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p=0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months,

p<0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p=0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p<0.001). Better survival was associated with Child-Pugh A liver function (p=0.013), with early response to two HAIC cycles (p=0.009), and with response (p=0.02) and disease control (p=0.001) after completing HAIC treatment. Addition of sorafenib did not provide a survival benefit (p=0.87). Conclusions: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.

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TENOFOVIR IS ASSOCIATED WITH A LOWER RISK OF MORTALITY IN HBV-RELATED HCC AFTER CURATIVE TREATMENT

Kai-Chun Chang1, Tung-Hung Su1,2 , Sih-Han Liao3, Shih-Wan Chou1 , Tai-Chung Tseng2,4, Hung-Chih Yang1 , Chen-Hua Liu1,2, Shih-Jer Hsu1,2 , Chun-Jen Liu1,2, Jia-Horng Kao1,2,5 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan2 Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan3 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan4 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan5 Tenofovir 與 B 型肝炎相關肝細胞癌接 受治癒性治療後較低死亡率相關

張凱鈞1 蘇東弘1,2 廖思涵3 周詩婉1 曾岱宗2,4 楊宏志1 劉振驊1,2 徐士哲1,2 劉俊人1,2 高嘉宏1,2,5 國立臺灣大學醫學院附設醫院內科部1 國立臺灣大學醫學院附設醫院肝炎研究中心2 國立臺灣大學醫學院附設癌醫中心分院綜合內科

部3 國立臺灣大學醫學院附設醫院醫學研究部4 國立臺灣大學醫學院臨床醫學研究所5

Background: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) can reduce the risk of hepatocellular carcinoma (HCC) in patients of chronic hepatitis B. Aims: This study aims to compare the difference between ETV and TDF on risk of HCC recurrence and mortality in patients with HBV-related HCC after curative treatment. Methods: Patients with HBV-related HCC who received curative treatment (surgery or radiofrequency ablation [RFA]) and promptly underwent long-term ETV or TDF therapy were retrospectively included. Baseline characteristics including age, sex, BMI, treatment modality, regimen and timing of antiviral therapy, BMI, Child-Pugh score, alpha-fetoprotein (AFP), FIB-

4 index, tumor size, ALBI score and BCLC stage were obtained. The risk of tumor recurrence, allcause mortality and HCC-related mortality were compared between ETV and TDF usage. Results: Among 9923 newly diagnosed HCC patients, we identified 314 HBV-related HCC patients post curative treatment for HCC and treated with ETV(n=264) or TDF(n=50) between January 2011 and December 2020. The mean age was 59, and 303 patients were male. After a median follow-up of 18.6 months, 145 patients developed recurrent HCC and 78 patients died. The baseline characteristics and severity of liver disease at curative treatment were comparable between ETV and TDF groups, except more patients received RFA in the TDF group and more patients initiated NUCs after curative treatment in the TDF group. After adjustment of confounding factors, the risks of HCC recurrence were comparable between TDF and ETV, either early (< 2 years) or late recurrence (> 2years). Compared to ETV group, TDF users had significantly lower allcause mortality (adjusted hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17-0.96, P=0.04), and trends of lower HCC-related mortality (adjust HR: 0.34, 95% CI: 0.10-1.13, P=0.08). Conclusions: TDF therapy is associated with a significantly reduced risk of all-cause mortality and a trend of lower HCC-related mortality among patients with HBV-related HCC after curative treatment.

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EFFICACY OF SYSTEMIC TREATMENT FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA ASSOCIATED WITH NON-VIRAL HEPATITIS ETIOLOGY

Chi-Jung Wu1,2, Pei-Chang Lee1,3,4 , Ya-Wen Hung1, Chieh-Ju Lee1, Chen-Ta Chi1,2 , I-Cheng Lee1,3, Ming-Chih Hou1,3 , Yi-Hsiang Huang1,2,3 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan2 Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan3 Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan4 非病毒性肝炎相關不可手術切除晚期 肝癌全身性藥物治療療效分析

吳啟榮1,2 李沛璋1,3,4 洪雅文1 李杰如1 齊振達1,2

李懿宬1,3 侯明志1,3 黃怡翔1,2,3 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學臨床醫學研究所2 國立陽明交通大學醫學院醫學系3 國立陽明交通大學藥理學研究所4

Background: Recent study showed unresectable hepatocellular carcinoma (uHCC) associated with non-viral hepatitis etiology has worse survival benefit compared with HCC associated with viral hepatitis in immunotherapy with immune checkpoint inhibitors (ICIs). However, the treatment response of sorafenib, the previous standard 1stline treatment, in this subgroup of patients is also still unclear. Aims: This study aimed to delineate the outcomes of different systemic treatments, including sorafenib and ICIs, for uHCC associated with non-viral hepatitis, and also identify predictors associated with outcomes. Methods: Eighty-three patients with non-viral hepatitis related uHCC who received sorafenib or ICIs as 1st-line treatment in Taipei Veterans General Hospital between January 1, 2017 and May 31, 2021 were retrospectively enrolled.