Pretransplant Functional Status Predicts Postoperative Morbidity and Mortality after Liver Transplantation in Patients with Cirrhosis

Background/Aims@#This study aimed to investigate whether pretransplant frailty can predict postoperative morbidity and mortality after liver transplantation (LT) in patients with cirrhosis. @*Methods@#We retrospectively reviewed 242 patients who underwent LT between 2018 and 2020 at a tertiary hospital in Korea. @*Results@#Among them, 189 patients (78.1%) received LT from a living donor. Physical frailty at baseline was assessed by the Short Physical Performance Battery (SPPB), by which patientswere categorized into two groups: frail (SPPB <10) and non-frail (SPPB ≥10). Among the whole cohort (age, 55.0±9.2 years; male, 165 [68.2%]), 182 patients were classified as non-frail and 60 patients were classified as frail. Posttransplant survival was shorter in the frail group than the non-frail group (9.3 months vs 11.6 months). Postoperative intensive care unit stay was longer in the frail group than in the non-frail group (median, 6 days vs 4 days), and the 30-day complication rate was higher in the frail group than in the non-frail group (78.3% vs 59.3%). Frailty was an independent risk factor for posttransplant mortality (adjusted hazard ratio, 2.38; 95% confidence interval, 1.02 to 5.57). In subgroup analysis, frail patients showed lower posttransplant survival regardless of history of hepatocellular carcinoma and donor type. @*Conclusions@#Assessment of pretransplant frailty, as measured by SPPB, provides important prognostic information for clinical outcomes in cirrhotic patients undergoing LT.

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.

Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective

Hepatocellular carcinoma (HCC) is a major cause of death in many countries, including South Korea. To provide useful and sensible advice for clinical management of patients with HCC, the Korean Liver Cancer Association and National Cancer Center Korea Practice Guideline Revision Committee have recently revised the practice guidelines for HCC management. However, there are some differences between practice guidelines and real-life clinical practice. In this review, we describe some key recommendations of the 2022 version of practice guidelines and the real-life clinical situation in South Korea, together with discussion about efforts needed to reduce the difference between guidelines and real-life clinical practice.

Laparoscopic Hepatic Resection Versus Laparoscopic Radiofrequency Ablation for Subcapsular Hepatocellular Carcinomas Smaller Than 3 cm: Analysis of Treatment Outcomes Using Propensity Score Matching

Objective@#To compare the therapeutic outcomes of laparoscopic hepatic resection (LHR) and laparoscopic radiofrequency ablation (LRFA) for single subcapsular hepatocellular carcinoma (HCC). @*Materials and Methods@#We screened 244 consecutive patients who had received either LHR or LRFA between January 2014 and December 2016. The feasibility of LRFA in patients who underwent LHR was retrospectively assessed by two interventional radiologists. Finally, 60 LRFA-feasible patients who had received LHR and 29 patients who had received LRFA as the first treatment for a solitary subcapsular HCC between 1 cm and 3 cm were finally included. We compared the therapeutic outcomes, including local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) between the two groups before and after propensity score (PS) matching. Multivariable Cox proportional hazard regression was also used to evaluate the difference in OS and RFS between the two groups for all 89 patients. @*Results@#PS matching yielded 23 patients in each group. The cumulative LTP and OS rates were not significantly different between the LHR and LRFA groups after PS matching (p = 0.900 and 0.003, respectively). The 5-year LTP rates were 4.6% and 4.4%, respectively, and OS rates were 100% and 90.7%, respectively. The RFS rate was higher in LHR group without statistical significance (p = 0.070), with 5-year rates of 78.3% and 45.3%, respectively. OS was not significantly different between the LHR (reference) and LRFA groups in multivariable analyses, with a hazard ratio (HR) of 1.33 (95% confidence interval, 0.12–1.54) (p = 0.818). RFS was higher in LHR (reference) than in LRFA without statistical significance in multivariable analysis, with an HR of 2.01 (0.87–4.66) (p = 0.102). @*Conclusion@#There was no significant difference in therapeutic outcomes between LHR and LRFA for single subcapsular HCCs measuring 1–3 cm. The difference in RFS should be further evaluated in a larger study.

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.

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.

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.

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.

Intraindividual Comparison between Gadoxetate-Enhanced Magnetic Resonance Imaging and Dynamic Computed Tomography for Characterizing Focal Hepatic Lesions: A Multicenter, Multireader Study

OBJECTIVE: To compare the diagnostic accuracy of dynamic computed tomography (CT) and gadoxetate-enhanced magnetic resonance imaging (MRI) for characterization of hepatic lesions by using the Liver Imaging Reporting and Data System (LI-RADS) in a multicenter, off-site evaluation.MATERIALS AND METHODS: In this retrospective multicenter study, we evaluated 231 hepatic lesions (114 hepatocellular carcinomas [HCCs], 58 non-HCC malignancies, and 59 benign lesions) confirmed histologically in 217 patients with chronic liver disease who underwent both gadoxetate-enhanced MRI and dynamic CT at one of five tertiary hospitals. Four radiologists at different institutes independently reviewed all MR images first and the CT images 4 weeks later. They evaluated the major and ancillary imaging features and categorized each hepatic lesion according to the LI-RADS v2014. Diagnostic performance was calculated and compared using generalized estimating equations.RESULTS: MRI showed higher sensitivity and accuracy than CT for diagnosing hepatic malignancies; the pooled sensitivities, specificities, and accuracies for categorizing LR-5/5V/M were 59.0% vs. 72.4% (CT vs. MRI; p < 0.001), 83.5% vs. 83.9% (p = 0.906), and 65.3% vs. 75.3% (p < 0.001), respectively. CT and MRI showed comparable capabilities for differentiating between HCC and other malignancies, with pooled accuracies of 79.9% and 82.4% for categorizing LR-M, respectively (p = 0.139).CONCLUSION: Gadoxetate-enhanced MRI showed superior accuracy for categorizing LR-5/5V/M in hepatic malignancies in comparison with dynamic CT. Both modalities had comparable accuracies for distinguishing other malignancies from HCC.

Disease Characteristics and Change in Arthritis Activity according to Treatment in Hepatitis B Surface Antigen-positive Rheumatoid Arthritis Patients: a Retrospective Chart Review Study

BACKGROUND: Rheumatoid arthritis (RA) treatment may differ according to hepatitis B state and consequently may bring about different arthritis outcomes. However, whether hepatitis B affects treatment outcome remains unclear. We investigated differences in change in arthritis activity between RA patients according to concomitant hepatitis B virus infection. METHODS: A retrospective medical chart review was performed by two rheumatologic fellows using single center data, from January 2000 to March 2015. Among RA patients older than 18 years, patients with comorbidities that could affect RA treatment aside from hepatitis B were excluded. Using 1:3 propensity score matching, 40 hepatitis B virus surface antigen (HBsAg)-positive patients and 112 HBsAg-negative patients were included in the study. Data were collected longitudinally using standardized electronic forms. The longitudinal relationship between HBsAg-positivity and RA activity was analyzed using generalized estimating equations. RESULTS: RA activity showed time-dependent improvement. Reductions of swollen joint count over time were significantly larger in the HBsAg-negative group. However, changes in disease activity score in 28 joints with three variables (DAS28-3), tender joint count, erythrocyte sedimentation rate and C-reactive protein level did not differ between the groups. There were no differences in alanine aminotransferase level. HBsAg-positive patients were less likely to receive methotrexate (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04–0.19; P < 0.001) and more likely to receive sulfasalazine (OR, 3.67; 95% CI, 1.94–6.95; P < 0.001). CONCLUSION: RA medication use varied according to HBsAg-positivity. However, improvement in RA activity was not significantly affected by concomitant hepatitis B infection.

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.

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.

Current status and strategies for viral hepatitis control in Korea

Viral hepatitis is one of major global health challenges with increasing disease burden worldwide. Hepatitis B virus and hepatitis C virus infections are major causes of chronic liver diseases. They can lead to cirrhosis, hepatocellular carcinoma, and death in significant portion of affected people. Transmission of hepatitis B virus can be blocked by vaccination. Progression of hepatitis B virus-related liver diseases can be prevented by long-term viral suppression with effective drugs. Although vaccine for hepatitis C virus is currently unavailable, hepatitis C virus infection can be eradicated by oral direct antiviral agents. To eliminate viral hepatitis, World Health Organization (WHO) has urged countries to develop national goals and targets through reducing 90% of new infections and providing universal access to key treatment services up to 80%. This can lead to 65% reduction of viral hepatitis-related mortality. Here, we discuss some key features of viral hepatitis, strategies to control viral hepatitis suggested by WHO, and current status and strategies for viral hepatitis control in South Korea. To achieve the goal of viral hepatitis elimination by 2030 in South Korea, an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention (CDC) needs to be established to organize and execute comprehensive strategy for the management of viral hepatitis in South Korea.

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.

Life-sustaining treatment and palliative care in patients with liver cirrhosis - legal, ethical, and practical issues

With the enactment of the ‘Act on Decisions on Life-Sustaining Treatment for Patients in Hospice and Palliative Care or at the End of Life’ (Act No. 14013) in Korea, there is growing concern about the practicality of this law. In this review, we discuss definitions, ethics, and practical issues related to this law.

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.

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.

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.

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.