Real-World Sustained Virologic Response Rates (SVR12) with Interferon (IFN)-Free Direct Acting Antiviral (DAA) Therapy in East Asia- Results from REAL-C (Real-World Effectiveness from the Asia Liver Consortium for Chronic Hepatitis C)

( Mindie H. Nguyen ),( Norihiro Furusyo ),( Dae Won Jun ),( Ming-Lung Yu ),( Jia-Horng Kao ),( Masaru Enomoto ),( Eiichi Ogawa ),( Etsuko Ilio ),( Chen-Hua Liu ),( Akihiro Tamori ),( Chia-Yen Dai ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Since their recent introduction in Asia, IFN-free DAAs have revolutionized treatment of chronic hepatitis C across all HCV genotypes. However, experience from large and diverse routine clinical practice is still limited. The aim of this study was to report real-world outcomes from a large multinational co hort of East Asian HCV patients treated with IFN-free DAAs. Methods: Data were obtained using a required case report form from the REAL-C registry of patients who were initiated on IFN-free DAA therapy in routine practice and represented 10 study centers inclusive of 30 clinical sites in Hong Kong, Japan, Korea, and Taiwan. Cirrhosis was determined by liver biopsy, noninvasive tests (elastography/fibroscan, fibrotest), or the presence of clinical, radiologic, endoscopic, laboratory evidence of cirrhosis and/or portal hypertension. Results: A total of 3702 patients have been registered. Table 1 displays the patient characteristics. The average age was 63.6±12.8; 17.7% had diabetes, 8.7% had chronic renal impairment, 26% had cirrhosis (5.1% decompensated cirrhosis), and 5.4% had HCC at baseline or prior to DAA treatment initiation. The majority of patients were HCV GT1 (68.7%), followed by HCV GT2 (30.4%). Ten different DAA regimens were used, with the majority receiving LDV/SOF (43.7%), followed by SOF+RBV (27.8%). One-third were treatment experienced (24.8% with prior PEG-IFN+RBV, 4.5% with prior DAA). SVR12 overall rate was 96.6%. Significant decreases noted in all major liver enzymes at week 12 and 24 post treatment. No increase in creatinine noted across treatments; 3.2% stopped treatment and 13.4% had an adverse event with fatigue (5.6% in patients treated with RBV vs. 6.4% in those treated without RBV, P=0.61) and anemia (5.6%) the most reported. Table 2 displays SVR12 rates by cirrhosis and prior treatment status for the most commonly used DAA treatments for GT1 and GT2 patients. SVR12 rates were excellent ranging from 97.1% (95%CI: 94.1-98.8%) to 99.7% (95%CI: 99.0-99.9%) for GT1 patients treated with LDV/SOF who did not have cirrhosis regardless of prior treatment history and who were treatment-naive with cirrhosis but lower in the cirrhotic treatment-experienced group (92.2%; 95%CI: 86.7-95.9%) (P<0.0001). Sub-analysis results for GT1b were similar, with SVR12 99.7% for non-cirrhotic treatment-naive, 99.5% for non-cirrhotic treatment-experienced, 97.4% for cirrhotic treatment-naive, and 93.0% for cirrhotic treatment-experienced, (P<0.0001). For GT2 patients, SVR12 was excellent for all groups (96.8-98.0%) except for cirrhotic treatment-experienced patients (n=66) who experienced an SVR12 of 87.9% (95%CI: 77.5-94.6%) (P=0.002). Conclusions: HCV cure rates were high overall in the REALC cohort-LDV/SOF GT1 98%; SOF+RBV GT2 96% except for cirrhotic, treatment-experienced patients especially in GT2, suggesting alternative therapy is needed.

Response to DAA in HCV Patients with HCC from East Asia: A REAL-C Study with Propensity Score Matching (PSM)

( Mindie H. Nguyen ),( Norihiro Furusyo ),( Dae Won Jun ),( Ming-Lung Yu ),( Jia-Horng Kao ),( Masaru Enomoto ),( Eiichi Ogawa ),( Etsuko Ilio ),( Chen-Hua Liu ),( Akihiro Tamori ),( Chia-Yen Dai ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Reports suggest HCV-HCC patients do not respond as well to the IFN-free DAAs, but background risks and confounders for treatment failures may not have been adequately controlled. Our goal was to compare SVR12 of DAAs in East Asian patients with HCV-HCC to those without HCC using PSM to balance the HCC and non-HCC groups. Methods: Data were from 10 study centers comprising of 30 clinical sites in Hong Kong, Japan, Korea, and Taiwan representing the Real-World Evidence from the Asia Liver Consortium for Chronic Hepatitis C (REAL-C) - a registry of patients treated with IFN-free DAAs in routine practice (n=3702). 1:1 PSM matching on cirrhosis, prior treatment, baseline platelet, age, sex, baseline HCV RNA, treatment regimen, baseline ALT, HCV genotype, and BMI was used to balance the groups at baseline. Results: In our cohort, there were 195 patients with HCC at baseline or prior to DAA initiation and 3507 patients who did not have HCC at baseline. Prior to PSM, HCC patients were significantly older, more likely male, more likely to have renal insufficiency, cirrhosis, and decompensation (all P< 0.004). After PSM, there were 171 HCC and N=171 non-HCC patients for analysis. As shown in Table 1, there were no significant differences in the baseline characteristics between the matched HCC and non-HCC cohorts. The majority (51-55%) of both groups received LDV/SOF; eight (three HCC, five non-HCC) stopped treatment before completion while ~10-12% had an adverse reaction (most common: anemia [ >~5-6%] and fatigue [~3-5%]). There were seven deaths: five in the HCC group (four were liver-related) and two in the non-HCC group (both were non-liver-related). Overall, SVR12 rate was >96% for both groups with no significant differences. (Table 2) Conclusions: This PSM study compared treatment for HCV patients with/without HCC, finding no difference in treatment tolerability, completion, and cure rates.

Opportunities for 2-[18F] Fluoro-2-Deoxy-D-Glucose PET/CT in Cervical-Vaginal Neuroendocrine Carcinoma: Case Series and Literature Review

Yin Lin,Wan Y. Lin,Ji A. Liang,Yu Y. Lu,Hsin Y. Wang,Shih C. Tsai,Chia H. Kao 대한영상의학회 2012 Korean Journal of Radiology Vol.13 No.6

Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation. Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.