Extremely Rare Risk of Hepatocellular Carcinoma after Naturally and Nucleos(t)ide Analogue Induced Hepatitis B Surface Antigen Seroclearance

( Sukhyeon Jeong ),( Sunghwan Yoo ),( Eunseo Lee ),( In Jung Kim ),( Sora Kim ),( Hye Young Chang ),( Jung Il Lee ),( Kwan Sik Lee ),( Hyun Woong Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Despite a favorable clinical course, the risk of hepatocellular carcinoma (HCC) still exists in patients achieving HBsAg seroclearance. Previous study has shown that the cumulative incidence rates of HCC at 5 years after HBsAg seroclearance were 1.5%. Therefore, we investigated to the incidence of HCC after naturally and nucleos(t)ide analogue (NA) induced HBsAg seroclearance in real-life clinical practice. Methods: A cohort study was conducted using data from Gangnam Severance Hospital. We identified all subjects with positive HBsAg between January 1, 2001 and March 21, 2018. NA use, liver biochemistries, serial HBsAg and anti-HBs results were retrieved. The primary endpoint was the incidence of HCC after naturally and NA induced HBsAg seroclearance. Results: A total of 109 chronic hepatitis B patients with HBsAg seroclearance were included for analysis. Among them, 24 patients were excluded. HBsAg seroclearance was developed after liver transplantation in 13 patients and after the development of HCC in 11 patients. In patients with spontaneous HBsAg seroclearance (n=51), all patients had confirmed HBsAg seroclearance and there was no HBsAg seroreversion. In patients with NA-induced HBsAg seroclearance (n=34), all patients had confirmed HBsAg seroclearance and HBsAg seroreversion was observed in just one patients (male, 37years, heavy alcoholics). At a mean follow-up of 9 years, there was no incidence of HCC in patients with naturally and NA-induced HBsAg seroclearance. Conclusions: The incidence of HCC was extremely rare after naturally and nucleos(t)ide analogue (NA) induced HBsAg seroclearance in real-life clinical practice. NA-induced HBsAg seroclearance is also as durable as naturally HBsAg seroclearance.

The Overall Survival of Hepatocellular Carcinoma after Resection According to the Cause of Liver Disease

( Eunseo Lee ),( Sunghwan Yoo ),( Sukhyeon Jeong ),( In-jung Kim ),( Sora Kim ),( Hye Young Chang ),( Jung Il Lee ),( Kwan Sik Lee ),( Hyun Woong Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Some studies have shown a poor prognosis for hepatocellular carcinoma (HCC) patients whose etiology is viral. This study is to evaluate the outcomes of the patients diagnosed to resectable HCC, according to the etiology of the disease due to the differences in prognosis between viral and non-alcoholic fatty liver disease (NAFLD). Methods: A total of 264 patients who received hepatectomy for the treatment of HCC between 2005 and 2019 were performed a review of medical records. They were divided into groups according to the cause of liver disease, followed by overall and disease-free survival analysis for comparison. Results: The cause of HCC consisted of 222 hepatitis B virus (HBV) (69.4%), 14 hepatitis C virus (HCV) (4.4%), and 28 non-alcoholic steatohepatitis (NASH) (7.9%). There was no statistically significant difference in the sex, tumor stage (BCLC and AJCC 7th) of the groups of patients divided according to the etiology of HCC. However, the mean age was higher in NAFLD (NAFLD 72 years, vs. HBV 62 years, HCV 68 years, P<0.001). The presence of liver cirrhosis was lower in NAFLD (NAFLD 14.3%, vs. HBV 51.8%, HCV 50%, P=0.001). Overall survival (OS) at five years of the patients with HBV, HCV and NAFLD were 88.2%, 74.1%, and 74.6%, respectively (P=0.031). Disease-free survival at five years of patients with HBV, HCV and NAFLD were 72.5%, 69.3%, and 77.9%, respectively (P=0.370). In multivariate analysis, age and baseline AFP were the significant prognostic factors of OS (hazard ratio [HR] for age; 0.938, confidential interval; 0.886-0.994, P=0.03, HR for AFP; 1.000; 1.000-1.000, P=0.001). Conclusions: Baseline age and AFP levels showed significant prognostic differences among the groups of HCC patients of the various etiologies. NAFLD induced HCC had shown slightly lower OS at five years than viral induced HCC.

The Efficacy and Safety of Concurrent Chemoradiotherapy in Patients with Unresectable Hepatocellular Carcinoma

( Sunghwan Yoo ),( Eunseo Lee ),( Sukhyeon Jeong ),( In-jung Kim ),( Jung Il Lee ),( Kwan Sik Lee ),( Hyun Woong Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Treatment responses of unresectable hepatocellular carcinoma (HCC) remain unacceptably low and treatment modalities are limited. We compared the efficacy and safety of concurrent chemoradiotherapy (CCRT). Methods: In retrospective cohort study, data on 74 patients with unresectable HCC, with Child-Turcotte-Pugh (CTP) scores of 5-8, were collected from a university hospital between January 2009 and October 2018. All patients were treated with CCRT (5-fluorouracil 500mg/㎡ via intraarterial chemoport at Day 1 to 5 and Day 20 to 25, plus radiotherapy 6,250 cGy/25 times at Day 1 to 25). Results: From 74 patients with unresectable HCC, 71.6% were classified as Child-Pugh (CP)-A, 86.4% as Barcelona Clinic Liver Cancer (BCLC)-C. The median overall survival (OS) and time to progression (TTP) were 13 months, and 8 months in the CCRT group. In univariate analysis, operation, ECOG, Child-Pugh score, diffuse type, main portal vein invasion, bile duct invasion, albumin, PT, HBV DNA were significant prognostic factors of OS (P=0.014, 0.005, 0.024, 0.029, 0.012, 0.008, 0.017, 0.000, 0.023), whereas operation, antiviral agent, ECOG, Child-Pugh score, age, creatinine, albumin, HBV DNA, PIVKA-II were significant prognostic factors of TTP (P=0.000, 0.008, 0.012, 0.031, 0.023, 0.023, 0.024, 0.024, 0.006). In multivariate analysis, operation, diffuse type, ECOG were significant prognostic factors of OS (P=0.028, 0.037, 0.043), whereas operation, antiviral agent, Child-Pugh score were significant prognostic factors of TTP (P=0.008, 0.044, 0.037). Major complications included hyperbilirubinemia (44.8%), ALT elevation (34.5%), ascites (13.8%), gastric ulcer (14.5%), catheter-related complications (3.4%) and radiation pneumonitis (2.3%). Conclusions: For managing unresectable HCC, CCRT may be a valuable and safe treatment modality.

Low Incidence of Hepatocellular Carcinoma after Antiviral Therapy in Patients with Chronic Hepatitis C and Hemophilia

( In-jung Kim ),( Sunghwan Yoo ),( Eunseo Lee ),( Sukhyeon Jeong ),( Sora Kim ),( Jung Il Lee ),( Kwan Sik Lee ),( Young Youn Cho ),( Hyung Joon Kim ),( Hyun Woong Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. the management of hepatitic C virus (HCV) infection and control of various complications are emerging as important factors to increase the long term prognosis of hemophilia patients. Therefore, we assessed the long term outcome of peginterferon plus rivavirin (PEG) and direct acting antivirals (DAA) in HCV patients with hemophilia. Methods: Patients (n=205) were enrolled between March 2007 and July 2019. 141 patients were treated with PEG (genotype 1, n=98; genotype 2, n=42; genotype 3a, n=1). 64 patients were treated with DAA (genotype 1, n=44; genotype 2, n=19; genotype 4, n=1). We evaluated sustained virological response (SVR), incidence of hepatocellular carcinoma (HCC). Results: Mean follow-up periods were 9.9 and 3.4 years in PEG and DAA, respectively. In genotype 1, SVR was 66.3% (65/98) and 90.9% (40/44) in PEG and DAA groups, respectively. In genotype 2, the SVR was 73.8% (31/42) and 89.4% (17/19) in PEG and DAA groups, respectively. HCC developed in 3.5% (5/141) patients treated with PEG. Among them, the mean age was 77 (range 66-83) and 4 patients were genotype 1(genotype 1a : 1, genotype 1b : 3). 3 patients had liver cirrhosis and 2 out of 3 patients (Genotype 1a : 1, genotype 2 : 1) had SVR with PEG. 1 patient who had liver cirrhosis was treated with DAA after 4 years and achieved SVR. However, HCC occurred 2 years later. 3 patients died of brain hemorrhage, pneumonia and leukemia. Conclusions: PEG showed stable SVR and low incidence of HCC after SVR. Although the follow-up period is short, oral DAA treatment showed more stable SVR than PEG and no development of HCC after SVR in CHC patients with hemophilia.