Clinical Outcomes and Validation of Ursodeoxycholic Acid Response Scores in Patients with Korean Primary Biliary Cholangitis: A Multicenter Cohort Study

Background/Aims@#The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. @*Methods@#A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. @*Results@#After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCAresponse rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41(n=97). The area under the receiver operating characteristic curve of URS in predicting UDCAresponse was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed accordingto the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). @*Conclusions@#URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.

Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma

Purpose@#Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. @*Materials and Methods@#Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. @*Results@#Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). @*Conclusion@#High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients

Background/Aims@#Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown. @*Methods@#A total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed. @*Results@#During a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years. @*Conclusions@#The HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.

Clinical impact of healthcare-associated acquisition in cirrhotic patients with community-onset spontaneous bacterial peritonitis

Background/Aims@#Healthcare-associated (HCA) infection is a recently suggested new category of community-onset infections. The implications of HCA infections in terms of diagnosis, treatment, and outcomes of spontaneous bacterial peritonitis (SBP) are not well understood. We sought to delineate the differences between community-acquired (CA) SBP and HCA SBP with specific interest in the antimicrobial resistance of causative microorganisms and outcomes. @*Methods@#We conducted a retrospective cohort study of all SBP episodes with positive ascitic culture and/or blood culture from June 2000 to August 2011. Community-onset SBP episodes were included when they occurred within 48 hours after admission and were classified as CA SBP and HCA SBP based on the predefined criteria. @*Results@#A total of 188 episodes of community-onset SBP were analyzed (65.4% HCA SBP and 34.6% CA SBP). HCA SBP had a higher resistance rate to third-generation cephalosporin (6.8% vs. 1.6%, p = 0.168). The overall 30-day mortality was similar between both groups (37.4% vs. 41.5%, p = 0.638). The independent risk factors for 30-day all-cause mortality in community-onset SBP included high Child-Pugh score, acute kidney injury, and resistance to third-generation cephalosporins; HCA infection was not associated. @*Conclusions@#Hepatic functional status, renal dysfunction, and third-generation cephalosporin resistant pathogens more adversely affected the outcome of cirrhotic patients with community-onset SBP rather than HCA infection. The higher rate of third-generation cephalosporin resistance was notable in HCA SBP, which will require a novel approach to empirical antibiotic treatment selection in this population.

Potential etiology, prevalence of cirrhosis, and mode of detection among patients with non-B non-C hepatocellular carcinoma in Korea

Background/Aims@#We systematically evaluated the clinical characteristics, prevalence of cirrhosis, and mode of detection in virus-unrelated (non-B non-C, NBNC) hepatocellular carcinoma (HCC) patients in Korea. @*Methods@#A total of 447 consecutive treatment-naïve NBNC-HCC adult patients who were registered at the Samsung Medical Center HCC registry in Korea from 2010 to 2013 were analyzed. NBNC was defined as negative hepatitis B surface antigen and negative anti-hepatitis C virus antibody. Presence of cirrhosis was determined based on histological, radiological, endoscopic, and serologic results. Mode of detection was classified as either under surveillance, incidental, or symptomatic. @*Results@#Heavy alcohol use was the most common potential etiology in NBNCHCC (NBNC-A, alcohol) (59.7%). Ten patients had other identifiable causes (NBNC-O, other identifiable cause) such as autoimmune hepatitis. The rest (38.0%) had no-identifiable cause (NBNC-NA-NO, non-alcohol, no-other identifiable cause). In NBNC-NA-NO group, 83.5% (96/115) of patients with available hepatitis B core immunoglobulin G antibody (HBcIgG) showed HBcIgG positivity, and 80.6% (137/170) had metabolic risk factors (diabetes, obesity, hypertension, and/ or dyslipidemia). Cirrhosis was present in 90.0%, 70.4%, and 60.0% of NBNC-O, NBNC-A, and NBNC-NA-NO patients, respectively. The proportion of patients diagnosed under surveillance was 25.5% across all patients, with specific proportions being 80.0%, 27.7%, and 18.8% for NBNC-O, NBNC-A, and NBNC-NA-NO, respectively. @*Conclusions@#Among NBNC-HCC patients, heavy alcohol use or any other identifiable cause was not found in 38.0%. These NBNC-NA-NO HCC patients showed a high prevalence of HBcIgG positivity and metabolic risk factors, suggesting that prior hepatitis B virus infection and metabolic risk factors may be major contributing factors in the hepatocarcinogenesis in NBNC-NA-NO patients.

Comparison of outcome between liver resection, radiofrequency ablation, and transarterial therapy for multiple small hepatocellular carcinoma within the Milan criteria

Purpose@#Although surgical resection is usually considered for a single tumor, several reports have suggested that resection can be considered for multiple tumors. The objective of this study was to determine whether resection could provide better long-term outcome for patients with multiple hepatocellular carcinomas (HCCs) within Milan criteria. @*Methods@#A total of 276 patients with multiple HCCs within Milan criteria with liver function preserved who underwent resection, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) between 2009 and 2013 were analyzed. Propensity-score (PS) matching was conducted. @*Results@#Five-year overall survival (OS) and recurrence-free survival (RFS) were better in the resection group than that in the RFA or TACE group. Patients who underwent resection had more preserved liver function and different tumor characteristics compared to those received RFA or TACE. With similar baseline characteristics generated in the PS model, there was no difference in 5-year OS among 3 groups (79.5% vs. 72.3% or 62.0%, P = 0.232), but the 5-year RFS was better for patients who received resection than those who received RFA or TACE (51.9% vs. 22.0% or 0.0%, P < 0.001). Although the major complication rate was slightly higher than RFA or TACE, there was no significant difference between the 3 groups before and after PS matching. @*Conclusion@#Resection was associated with better RFS than RFA or TACE and showed comparable OS in multiple HCC patients within the Milan criteria, but at a cost of slightly increased risk of complication. Resection can be considered as a first-line option if selected appropriately.

Advanced Stage Hepatocellular Carcinoma Successfully Treated with Transarterial Radioembolization and Multi-tyrosine Kinase Inhibitor Therapy

Transarterial radioembolization (TARE) with yttrium-90 microspheres has become widely utilized in managing hepatocellular carcinoma (HCC). The utility of TARE is expanding with new insights through experiences from real-world practice and clinical trials, and recently published data suggest that TARE in combination with sorafenib may improve the overall survival in selected patients. Here, we report a case of advanced stage HCC that was successfully treated with TARE and sorafenib. The patient achieved complete response (CR) at 12 months after the initial treatment with TARE and sorafenib, followed by additional transarterial chemoembolization and proton beam therapy for local tumor recurrence at 19-month post-TARE. The patient was followed up every 3 months thereafter and still achieved CR both biochemically and radiologically for the following 12 months. A combination strategy of TARE and systemic therapy may be a useful alternative treatment option for selected patients with advanced stage HCC.

Importance of a Diversity Committee in Advancing the Korean Society of Gastroenterology: A Survey Analysis / 대한소화기학회지

BACKGROUND/AIMS: The numbers of women, young doctors, and foreigners in the medical field have increased continuously. On the other hand, the environment for these minority groups has not improved, particularly in Eastern countries. The authors aimed to increase the awareness of the importance of a Diversity Committee in the Korean Society of Gastroenterology (KSG) by an analysis of a survey. METHODS: From January to February in 2019, a survey was conducted on physicians and a few medical students by googling. The questionnaire consisted of the target doctors of the Diversity Committee, purpose, specific activities, and expected effects of Diversity Committee to the KSG. The participants requested to respond with yes/no or a 5-point scale. RESULTS: A total of 202 participants completed the questionnaire, and 93.5% (189/202) were medical specialists. The proportion of males was 61.9% (125/202), and 39.6% (80/202) and 36.1% (73/202) participants were in their 30s and 40s, respectively. A total of 174 participants (86.1%) agreed with the necessity of a Diversity Committee, and 180 participants (89.1%) answered this committee would help advance the KSG with significant differences between males and females (80.8% vs. 94.8%, p=0.006; 84.8% vs. 96.1%, p=0.011). Similarly, there were significant differences in the responses according to sex in most questions. CONCLUSIONS: Most participants of the survey expected a contribution of the Diversity Committee to the advancement of the KSG. On the other hand, in most of the priorities of the target, purpose, specific activities, and expected effects of the Diversity Committee, there was a difference in the perceptions between males and females. Therefore, continuous efforts are needed to reduce the differences within the KSG.

Importance of a Diversity Committee in Advancing the Korean Society of Gastroenterology: A Survey Analysis / 대한소화기학회지

BACKGROUND/AIMS: The numbers of women, young doctors, and foreigners in the medical field have increased continuously. On the other hand, the environment for these minority groups has not improved, particularly in Eastern countries. The authors aimed to increase the awareness of the importance of a Diversity Committee in the Korean Society of Gastroenterology (KSG) by an analysis of a survey.METHODS: From January to February in 2019, a survey was conducted on physicians and a few medical students by googling. The questionnaire consisted of the target doctors of the Diversity Committee, purpose, specific activities, and expected effects of Diversity Committee to the KSG. The participants requested to respond with yes/no or a 5-point scale.RESULTS: A total of 202 participants completed the questionnaire, and 93.5% (189/202) were medical specialists. The proportion of males was 61.9% (125/202), and 39.6% (80/202) and 36.1% (73/202) participants were in their 30s and 40s, respectively. A total of 174 participants (86.1%) agreed with the necessity of a Diversity Committee, and 180 participants (89.1%) answered this committee would help advance the KSG with significant differences between males and females (80.8% vs. 94.8%, p=0.006; 84.8% vs. 96.1%, p=0.011). Similarly, there were significant differences in the responses according to sex in most questions.CONCLUSIONS: Most participants of the survey expected a contribution of the Diversity Committee to the advancement of the KSG. On the other hand, in most of the priorities of the target, purpose, specific activities, and expected effects of the Diversity Committee, there was a difference in the perceptions between males and females. Therefore, continuous efforts are needed to reduce the differences within the KSG.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

PURPOSE: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. MATERIALS AND METHODS: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62–92 GyE10. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. CONCLUSION: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

Noninvasive Diagnostic Criteria of the Revised 2014 the Korean Liver Cancer Study Group and the National Cancer Center Guideline for Subcentimetersized Hepatocellular Carcinoma: Is It Too Strict?

BACKGROUND/AIMS: Noninvasive diagnostic criteria for hepatocellular carcinoma (HCC) differ between guidelines, especially for subcentimeter-sized nodules. This study aimed to analyze clinical and radiological characteristics of subcentimeter-sized HCC, and assess the validity of noninvasive diagnostic criteria of the revised 2014 the Korean Liver Cancer Study Group and the National Cancer Center (KLCSG-NCC) guideline for subcentimeter-sized HCC. METHODS: A total of 33 consecutive patients (median age, 58.6 years; men, 60.6%; hepatitis B virus-infected, 87.9%) who were diagnosed with HCC between January 2009 and December 2013 and had a maximum tumor diameter less than 1 cm were retrospectively included. RESULTS: Among 33 subcentimeter-sized HCC cases, 6 cases were histologically proven and the remaining 27 patients were diagnosed by radiologically and/or serologically. Initial detection modality was dynamic contrast-enhanced computed tomography (CT) (66.7%, 22/33) or dynamic contrast-enhanced magnetic resonance imaging (MRI) (33.3% 11/33). No case was identified by surveillance ultrasonography. Typical radiological feature of HCC, which is arterial enhancement with delayed washout, was present in 51.7% (15/29 patients) in dynamic contrast-enhanced CT, and 90.9% (30/33 patients) in dynamic contrast-enhanced MRI. When these 33 cases were re-assessed by the revised 2014 KLCSG-NCC guideline, no one has fulfilled the noninvasive diagnostic criteria. CONCLUSIONS: None of the cases that were diagnosed as subcentimeter-sized HCC including histologically confirmed cases did not fulfill the noninvasive diagnostic criteria of the revised 2014 KLCSG-NCC guideline. Refinement of the current noninvasive diagnostic criteria for subcentimeter-sized HCC may be required.

The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE

BACKGROUND/AIMS: We investigated the outcomes of early-stage hepatocellular carcinoma (HCC) patients who showed a complete response (CR) to initial transarterial chemoembolization (TACE), with a focus on the role of scheduled TACE repetition. METHODS: A total of 178 patients with early-stage HCC who were initially treated with TACE and showed a CR based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria on one month follow-up computed tomography (CT) were analyzed. Among them, 90 patients underwent scheduled repetition of TACE in the absence of viable tumor on CT. RESULTS: During a median follow-up period of 4.6 years (range: 0.4-8.8 years), mortality was observed in 71 patients (39.9%). The overall recurrence-free and local recurrence-free survival rates at 1 year were 44.4% and 56.2%. In the multivariable model, scheduled repetition of TACE was an independent factor associated with survival (hazard ratio [95% confidence interval]: 0.56 [0.34-0.93], P=0.025). When stratified using Barcelona clinic liver cancer (BCLC) stage, scheduled repetition of TACE was associated with a favorable survival rate in BCLC stage A patients, but not in BCLC 0 patients. CONCLUSIONS: Scheduled repetition of TACE was associated with better survival for early-stage HCC patients showing a CR after initial TACE, especially in BCLC stage A patients.

A Novel Model for Predicting Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B and Normal Alanine Aminotransferase Levels

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) can develop in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels. Therefore, methods that can stratify an individual's HCC risk are needed. METHODS: A simple HCC risk score was developed from 971 patients with CHB who had elevated hepatitis B virus DNA levels (>2,000 IU/mL) with normal or mildly elevated ALT levels (<80 U/L). The score was validated from an independent cohort of 507 patients. RESULTS: A 4-point risk scale was developed, with HCC risk ranging from 0% to 17.8% at 5 years for the lowest and highest risk scores. The D2AS score had high area under the receiver operating curves (AUROCs) for predicting development of HCC at 3/5 years (0.895/0.884). The calculated AUROCs to predict the development of HCC at 3/5 years were 0.889/0.876 in the validation cohort, with 5-year HCC incidence rates ranging from 0% to 13.8% at 5 years for the lowest and highest risk scores. CONCLUSIONS: The D2AS risk score can play a valuable role in risk stratification and may be useful for guiding clinical decisions for enhanced surveillance or treatment to reduce the HCC risk in CHB patients with normal or mildly elevated ALT levels.

Long-term real-world entecavir therapy in treatment-naïve hepatitis B patients: base-line hepatitis B virus DNA and hepatitis B surface antigen levels predict virologic response

BACKGROUND/AIMS: Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance. We aimed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response, including quantitative hepatitis B surface antigen (qHBsAg) levels. METHODS: One thousand and nine treatment-naïve chronic hepatitis B (CHB) patients were evaluated for cumulative rates of virologic response, biochemical response, and entecavir mutations. The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment. RESULTS: The median duration of entecavir treatment was 26.5 months. The cumulative rate of virologic response at years 1, 3, and 5 were 79.0%, 95.6%, and 99.4%, respectively. The cumulative rate of entecavir resistance was 1.0% and 2.1% in years 3 and 5. Multivariate analysis identified baseline hepatitis B e antigen (HBeAg) negative status (p < 0.001) and lower hepatitis B virus (HBV) DNA (p < 0.001) as predictors of virologic response. Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg. There were no serious adverse events during treatment. CONCLUSIONS: Long-term entecavir treatment of nucleos(t)ide-naïve CHB patients was associated with an excellent virologic response and a low rate of entecavir-resistant mutations at 5 years. Baseline HBV DNA load, qHBsAg levels, and HBeAg status were predictors of virologic response during entecavir treatment.

The Clinical Significance of Serum Alpha-fetoprotein in Diagnosing Hepatocellular Carcinoma in a Health Screening Population / 대한소화기학회지

BACKGROUND/AIMS: Serum alpha-fetoprotein (AFP) measurement is commonly included in a health check-up program in Korea. However, its benefits remain uncertain. We analyzed whether AFP measurement should be included in a general health check-up program to screen for hepatocellular carcinoma (HCC). METHODS: A total of 36,552 adults aged 18 years or older—who participated in a routine health examination including AFP determination between January 2009 and December 2009 at the Health Promotion Center, Samsung Medical Center, South Korea—were analyzed. High risk of HCC was defined as positivity for hepatitis B surface antigen, anti-hepatitis C virus antibody or having liver cirrhosis. RESULTS: AFP level >10 ng/mL was observed in 27 participants (0.1%) and primary liver cancer was diagnosed in 9 patients (6 HCC and 3 cholangiocarcinoma). Among 1,619 participants with high risk factors of HCC, AFP level >10 ng/mL was observed in 16 participants, of which, 4 diagnoses were made. Sensitivity, specificity, positive predictive value, and negative predictive value of AFP for HCC was 0.66, 0.99, 0.25 and 0.99, respectively, for high risk participants. Among 34,933 participants without risk factors for HCC, 11 patients (<0.1%) showed elevated AFP levels above 10 ng/mL, and no case was diagnosed with primary liver cancer during a median follow-up period of 36 months (range: 0-48 months). CONCLUSIONS: AFP elevation was rare in participants without risk factors for HCC, and was unable to screen for HCC in this population. We discourage routine AFP measurements for asymptomatic adults without risk factors of HCC.

Transarterial chemoembolization versus resection for intermediate-stage (BCLC B) hepatocellular carcinoma

BACKGROUND/AIMS: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. METHODS: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. RESULTS: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1-B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo' (2-4) nodules of intermediate size (5-10 cm) when the AFP levels was <400 ng/ml, or ‘oligo' (2-4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). CONCLUSIONS: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.

Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Patients with Decompensated Cirrhosis / 대한소화기학회지

HCV-related decompensated liver cirrhosis is a life-threatening illness with an average 5-year survival rate of 50%. Because these patients have higher risk of morbidity and mortality including development of hepatocellular carcinoma, the benefits of eradicating the virus may be greater than in those with less-advanced disease. Recently, direct-acting antiviral agents (DAAs) are replacing interferon-based regimens that have serious adverse events and low tolerability in the treatment of HCV infection. Many clinical trials using combination of several DAAs with or without ribavirin are now actively on-going in HCV-related decompensated cirrhosis, and encouraging data are beginning to appear. In this review, recent advances in the treatment of HCV-related decompensated cirrhosis are introduced with special focus on new DAAs.

Prediction of the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients after Sustained Virological Response by Aspartate Aminotransferase to Platelet Ratio Index

BACKGROUND/AIMS: Following sustained virological response (SVR) for chronic hepatitis C (CHC) infection, patients with advanced fibrosis require regular monitoring for hepatocellular carcinoma (HCC). The aspartate aminotransferase to platelet ratio index (APRI) is a simple noninvasive surrogate marker known to reflect fibrosis. METHODS: We retrospectively analyzed 598 patients who achieved SVR with interferon-based therapy for CHC. RESULTS: Over a median of 5.1 years of follow-up, there were eight patients diagnosed with HCC and a 5-year cumulative incidence rate of 1.3%. The median pretreatment APRI was 0.83, which decreased to 0.29 after achieving SVR (p<0.001). Both the pre- and posttreatment indices were associated with HCC development. The 5-year cumulative HCC incidence rates were 0% and 2.8% for patients with pretreatment APRI <1.0 and ≥1.0, respectively (p=0.001) and 0.8% and 12.8% for patients with posttreatment APRI <1.0 and ≥1.0, respectively (p<0.001). Pretreatment APRI at a cutoff of 1.0 had a 100% negative predictive value until 10 years after SVR. CONCLUSIONS: HCC development was observed among CHC patients who achieved SVR. The pre- and post-treatment APRI could stratify HCC risk, indicating that the APRI could be a useful marker to classify HCC risk in CHC patients who achieved SVR. However, given the small number of HCC patients, this finding warrants further validation.

Clinical significance and predictive factors of early massive recurrence after radiofrequency ablation in patients with a single small hepatocellular carcinoma

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. METHODS: In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. RESULTS: During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. CONCLUSIONS: Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.