Showing papers by "Do Young Kim published in 2020"

Immunopathogenesis of ANCA-Associated Vasculitis.

Abstract: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.

Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase.

Abstract: Background Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. Aims To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. Methods In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. Results The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >107 IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P Conclusions The criterion of HBV-DNA level > 107 IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.

Hepatocellular Carcinoma Risk Steadily Persists Over Time Despite Long-Term Antiviral Therapy for Hepatitis B: A Multicenter Study

Abstract: Background: Long-term antiviral therapy (AVT) for chronic hepatitis B (CHB) reduces the risk of hepatocellular carcinoma (HCC). We assessed the temporal trends in the incidence of HCC over time during long-term AVT among Asian patients with CHB. Methods: Patients with CHB receiving entecavir/tenofovir (ETV/TDF) as a first-line antiviral were recruited from four academic hospitals in the Republic of Korea. We compared the incidence of HCC during and after the first 5 years of ETV/TDF treatment. Results: Among 3,156 patients, the median age was 49.6 years and males predominated (62.4%). During the follow-up, 9.0% developed HCC. The annual incidence of HCC per 100 person-years during the first 5 years (n = 1,671) and after the first 5 years (n = 1,485) was statistically similar (1.93% vs. 2.27%, P = 0.347). When the study population was stratified according to HCC prediction model, that is, modified PAGE-B score, the annual incidence of HCC was 0.11% versus 0.39% in the low-risk group ( 0.05). A Poisson regression analysis indicated that the duration of AVT did not significantly affect the overall trend of the incidence of HCC (adjusted annual incidence rate ratio = 0.85; 95% confidence interval, 0.66–1.11; P = 0.232). Conclusions: Despite long-term AVT, the risk of HCC steadily persists over time among patients with CHB in the Republic of Korea, in whom HBV genotype C2 predominates. Impact: Careful HCC surveillance is still essential.

A Survey on Churn Analysis in Various Business Domains

Abstract: In this paper, we present churn prediction techniques that have been released so far. Churn prediction is used in the fields of Internet services, games, insurance, and management. However, since it has been used intensively to increase the predictability of various industry/academic fields, there is a big difference in its definition and utilization. In this paper, we collected the definitions of churn used in the fields of business administration, marketing, IT, telecommunications, newspapers, insurance and psychology, and described their differences. Based on this, we classified and explained churn loss, feature engineering, and prediction models. Our study can be used to select the definition of churn and its associated models suitable for the service field that researchers are most interested in by integrating fragmented churn studies in industry/academic fields.

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study

Abstract: Background and Aims: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. Methods: Liver cirrhosis patients with Child–Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. Results: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221–0.684, p < 0.001). Conclusion: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.

Retrospective comparison of EASL 2018 and LI-RADS 2018 for the noninvasive diagnosis of hepatocellular carcinoma using magnetic resonance imaging.

Abstract: We compared the diagnostic performances of the European Association for the Study of the Liver (EASL) 2018 and Liver Imaging Reporting and Data System (LI-RADS) 2018 criteria on magnetic resonance imaging (MRI) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients and evaluated the difference in diagnostic value between MRI with extracellular contrast agents (ECA-MRI) and MRI with hepatobiliary agents (HBA-MRI). This study included 382 observations from 298 patients at high risk for HCC who underwent preoperative multiphasic contrast-enhanced MRI between January 2015 and December 2016. Two readers assessed all observations according to the EASL 2018 and LI-RADS 2018 criteria, and the per-observation diagnostic performances were compared. On ECA-MRI, the LR-5 category of LI-RADS 2018 showed significantly higher sensitivity (78.9% vs. 71.5%, p = 0.005) and accuracy (81.7% vs. 75.0%, p = 0.003) for the diagnosis of HCC than the EASL 2018. On HBA-MRI, the diagnostic performances of the EASL 2018 and LR-5 of LI-RADS 2018 were not significantly different. When using EASL 2018, no statistically significant differences were observed in the diagnostic performances between ECA-MRI and HBA-MRI; however, when using the LR-5 of LI-RADS 2018, ECA-MRI had a higher sensitivity (78.9% vs. 67.5%, p = 0.029) than HBA-MRI. On ECA-MRI, the LR-5 category of LI-RADS 2018 provides better sensitivity and accuracy than the EASL 2018 for diagnosing HCC. EASL 2018 provides comparable diagnostic performances between ECA-MRI and HBA-MRI, but the LR-5 category of LI-RADS 2018 provides better sensitivity on ECA-MRI than on HBA-MRI.

An optimized hepatocellular carcinoma prediction model for chronic hepatitis B with well-controlled viremia.

Abstract: Background and aims Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) substantially decreased in the era of potent antiviral therapy. We developed an optimized HCC risk prediction model for CHB with well-controlled viremia by nucelos(t)ide analogs (NUCs). Method We analysed those who achieved virological response (VR; serum HBV-DNA Results Among 1511 patients, 9.5% developed HCC. Cirrhosis on ultrasonography (adjusted HR [aHR] 2.47), age (aHR 1.04), male (aHR 1.90), platelet count 161) groups were more likely to develop HCC compared with the low-risk group (score ≤75) with statistical significances (HRs; 4.43 and 47.693 respectively; both P Conclusion CAMPAS model derived through comprehensive clinical evaluation of liver disease allowed the more delicate HCC prediction for CHB patients with well-controlled viremia by NUCs.

A survey on transarterial chemoembolization refractoriness and a real-world treatment pattern for hepatocellular carcinoma in Korea

Abstract: Background/aims Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but there is much controversy about TACE refractoriness. The aim of this study was to identify trends in the actual clinical application of TACE and recognition of TACE refractoriness by Korean experts. Methods In total, 17 questionnaires on TACE refractoriness were administered to 161 clinicians via an online survey. Multiple answers were allowed for some questions. Results Most clinicians agreed that there is a need for standardization of TACE application through specific scoring systems (n=124, 77.0%). TACE refractoriness was predominantly expected by participants when recurrences were detected within 1 month (n=70, 43.5%), there were 4 to 6 tumors (n=77, 47.8%), the maximal tumor size was 3-5 cm (n=49, 30.4%), and when there was insufficient tumor necrosis despite TACE being repeated more than three times (n=78, 48.4%). Overall, sorafenib therapy (n=137) and radiotherapy (n=114) were preferred when repeated TACE was considered ineffective. Conclusion Treatment of HCC is often based on the clinical judgment of clinicians because of the heterogeneity among individuals. Experts need to continue discussions on the standardization and sub-classification of HCC treatment guidelines in Korea.

Prognosis of Early-Stage Hepatocellular Carcinoma: Comparison between Trans-Arterial Chemoembolization and Radiofrequency Ablation.

Abstract: Radiofrequency ablation (RFA) is a curative treatment for early-stage hepatocellular carcinoma (HCC) ineligible for surgery or liver transplantation. However, trans-arterial chemoembolization (TACE) might be an alternative when RFA is contraindicated due to structural problems. Here, we aimed to compare their long-term outcomes. Treatment-naive HCC patients fulfilling the Milan criteria who underwent RFA (n = 136) or TACE (n = 268) were enrolled. Complete response (CR) and 5-year recurrence-free survival (RFS) rates were higher in the RFA group than in the TACE group (94.1% vs. 71.6% and 35.8% vs. 17.0%, respectively; both p < 0.001), whereas 5-year overall survival (OS) rates were not significantly different (65.5% vs. 72.3%, respectively; p = 0.100). Multivariate analysis showed that RFA was associated with better RFS (adjusted hazard ratio [aHR] 0.628; p = 0.001) than TACE, but not with better OS (aHR 1.325; p = 0.151). The most common 1st-line treatment after recurrence were TACE (n = 53), followed by RFA (n = 21) among the RFA group and TACE (n = 150), followed by RFA (n = 44) among the TACE group. After propensity-score matching, similar results were reproduced. Hence, TACE could be an effective alternative to RFA in terms of OS rates. However, TACE should be confined only to RFA-difficult cases, given its lower CR and RFS rates and multi-disciplinary approaches are desirable in decision-making.

Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein level predicts recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection

Abstract: Background/Aims: To investigate whether serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) can predict the recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. Methods: Patients with chronic hepatitis B (CHB) who underwent curative resection for HCC between 2004 and 2015 were eligible for the study. Recurrence was sub-classified as early (<2 years) or late (≥2 years). Results: A total of 170 patients with CHB were selected. During the follow-up period (median, 22.6 months), 64 (37.6%) patients developed recurrence. In multivariate analyses, WFA+-M2BP level was an independent predictor of overall (hazard ratio [HR]=1.490), early (HR=1.667), and late recurrence (HR=1.416), together with male sex, des-gamma carboxyprothrombin level, maximal tumor size, portal vein invasion, and satellite nodules (all P 2.14 experienced recurrence more frequently than those with a WFA+-M2BP level ≤2.14 (P=0.011 by log-rank test), and had poorer postoperative outcomes than those with a WFA+-M2BP level ≤2.14 in terms of overall recurrence (56.0 vs. 34.5%, P=0.047) and early recurrence (52.0 vs. 20.7%, P=0.001). Conclusions: WFA+-M2BP level is an independent predictive factor of HBV-related HCC recurrence after curative resection. Further studies should investigate incorporation of WFA+-M2BP level into tailored postoperative surveillance strategies for patients with CHB.

The Modified Response Evaluation Criteria in Solid Tumors (RECIST) Yield a More Accurate Prognoses Than the RECIST 1.1 in Hepatocellular Carcinoma Treated with Transarterial Radioembolization.

Abstract: Background/Aims: The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria have been used to assess treatment responses for hepatocellular carcinoma (HCC) patients. We investigated which criteria provides better survival predictions in HCC patients treated with transarterial radioembolization (TARE). Methods: In total, 102 patients with unresectable intrahepatic HCC, who were treated with TARE between 2012 and 2017, were reviewed retrospectively. The treatment response after TARE was evaluated at 1, 3, and 6 months by the mRECIST and RECIST 1.1. Responders were defined as patients with complete or partial responses by each criterion. Results: The median age of 83 men and 19 women was 64.3 years. The median alpha-fetoprotein and des-gamma-carboxy prothrombin levels were 37.1 ng/mL and 1,780.0 mAU/mL, respectively. The median maximal tumor size was 8.3 cm, and multiple tumors were observed in 36 patients (35.3%). During the follow-up period (median, 20.7 months), 21 patients (20.6%) died, with a mean survival time of 55.5 months. The cumulative survival rate was 96.1% at 6 months and 89.3% at 12 months. Responders, defined by the mRECIST at 1, 3, and 6 months after TARE, showed better survival outcomes than nonresponders (hazard ratio [HR]=5.736, p=0.008 at 1 month; HR=3.145, p=0.022 at 3 months, and HR=2.887, p=0.061 at 6 months). The survival rates of responders and nonresponders defined by the RECIST 1.1 were similar (all p>0.05). Conclusions: Response evaluations that use the mRECIST provide more accurate prognoses than those that use the RECIST 1.1 in HCC patients treated with TARE. (Gut Liver 2020;14:765-774)

Prevention and management of viral hepatitis in inflammatory bowel disease: a clinical practice guideline by the Korean Association for the Study of Intestinal Diseases.

Abstract: The treatment of inflammatory bowel disease (IBD) has been revolutionized for the last 10 years by the increasing use of immunomodulators and biologics. With immunosuppression of this kind, opportunistic infection is an important safety concern for patients with IBD. In particular, viral hepatitis is determined by the interaction between the virus and the host’s immunity, and the risk of reactivation increases if immunity is compromised by immunosuppression therapy. Parts of Asia, including Korea, still show intermediate endemicity for the hepatitis A virus and hepatitis B virus compared with the United States and Western Europe. Thus, members of IBD research group of the Korean Association for the Study of Intestinal Diseases have produced a guideline on the prevention and management of viral hepatitis in IBD. (Intest Res 2020;18:18-33)

Efficacy and Safety of Liver-Directed Concurrent Chemoradiotherapy and Sequential Sorafenib for Advanced Hepatocellular Carcinoma: A Prospective Phase 2 Trial

Abstract: Purpose Although sorafenib as a standard of care for advanced hepatocellular carcinoma (HCC) prolongs overall survival (OS), its efficacy is limited owing to its unsatisfactory objective response and marginal survival benefit. To counter these limitations, we designed a single-arm, phase II trial with liver-directed concurrent chemoradiotherapy (LD-CCRT) and sequential sorafenib treatment in patients with advanced HCC. Methods and Materials We enrolled advanced HCC patients diagnosed between 2014 and 2017 who were ineligible for curative treatment. During the first and last 5 days of 5-week radiation therapy, concurrent hepatic arterial infusion with 5-fluorouracil (500 mg/d) and leucovorin (50 mg/d) through an implanted port was administered 4 weeks after initiation of LD-CCRT and sequential sorafenib treatment (400 mg, twice daily). The primary endpoint was OS. This trial has been registered at clinicaltrials.gov . Results Among the enrolled patients (n = 47), objective response rates 4 weeks after LD-CCRT and during/up to sorafenib maintenance were 44.7% and 53.2%, respectively. Overall, 9 patients (19.1%) underwent curative resection or transplantation after down staging. The median radiation dose was 60 Gy. The median OS was 24.6 months for the entire cohort and 13.0 months for the subgroup with tumor invasion into the main portal trunk or its first branch, whereas the median progression-free survival for the cohort and subgroup was 6.8 and 5.6 months, respectively. The most frequent treatment-related adverse events were diarrhea (36.2%) and hand-foot skin reaction (34%), which were manageable with conservative treatment. Conclusions LD-CCRT and sequential sorafenib treatment provided favorable OS and progression-free survival with good tolerability. Tumor reduction using an initial LD-CCRT enabled down staging, subsequent curative treatment, and long-term survival in about 20% of the patients with advanced HCC. However, further randomized trials are required to confirm these results.

Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid arthritis: A retrospective monocentric study.

Abstract: Objectives: Comorbidities and conventional risk factors influence the prognosis of patients with rheumatoid arthritis (RA). We investigated whether liver fibrosis burden is associated with ...

Design and validation of risk prediction model for hepatocellular carcinoma development after sustained virological response in patients with chronic hepatitis C.

Abstract: OBJECTIVES Hepatocellular carcinoma can develop after hepatitis C virus eradication. We developed a new hepatocellular carcinoma risk score (HCC-SVR score) based on independent predictors for chronic hepatitis C after sustained virological response. METHODS Between 2003 and 2016, a total of 1193 patients with chronic hepatitis C who achieved sustained virological response through antiviral therapy were included (669 for training cohort and 524 for validation cohort). The HCC-SVR score was developed using multivariate Cox proportional hazards regression modelling. RESULTS Hepatocellular carcinoma (n = 19) occurred more frequently in older, male patients and was associated with liver cirrhosis; hypertension; diabetes; lower platelet count; higher alpha-fetoprotein, aspartate, and alanine aminotransferase; lower total cholesterol; and higher fibrosis-4 index (FIB-4) (all P < 0.05). FIB-4 (hazard ratio = 1.080), male gender (hazard ratio = 8.189), and higher alpha-fetoprotein (hazard ratio = 1.060) independently predicted hepatocellular carcinoma (all P < 0.05). HCC-SVR score successfully predicted hepatocellular carcinoma development risk [area under receiver operating characteristic curve (AUC) = 0.771, 0.857, and 0.911 at 2, 4, and 6 years, respectively]. The cumulative incidence rate of hepatocellular carcinoma differed significantly among groups stratified by HCC-SVR risk score (0-2 points, low; 3-7 points, intermediate; 8-9 points, high risk) (all P < 0.05 by log-rank test). HCC-SVR score was maintained in a validation cohort (n = 524) (AUC = 0.728 at 2 years, 0.737 at 4 years, and 0.809 at 6 years). CONCLUSION The HCC-SVR score enables risk stratification for hepatocellular carcinoma development at sustained virological response in patients with chronic hepatitis C.

Advanced Liver Fibrosis Predicts Unfavorable Long-Term Prognosis in First-Ever Ischemic Stroke or Transient Ischemic Attack.

Abstract: Introduction There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA). Objective We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA. Methods This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of >3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used. Results There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40-6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59-12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05-3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037). Conclusions The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA.

Sarcopenia Is Independently Associated with the Degree of Liver Fibrosis in Patients with Type 2 Diabetes Mellitus

Abstract: Background/Aims: Sarcopenia is associated with liver fibrosis in patients with nonalcoholic fatty liver disease and chronic hepatitis B. We investigated the association between sarcopenia and hepatic fibrotic burden in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM who had received a comprehensive medical health checkup were recruited. Muscle mass was assessed using computed tomography. Fibrotic burden was assessed using the fibrosis-4 index (FIB-4). The study population was divided by quartile stratification of the lumbar skeletal muscle index (LSMI). Results: Among 309 patients with T2DM, 75 (24.3%) had sarcopenia. These patients were significantly older and had higher FIB-4, whereas they had significantly lower body mass index (BMI) and LSMI than patients without sarcopenia (all p<0.05). The LSMI showed a significant negative correlation with the FIB-4 when analyzed in terms of quartile stratification (p=0.003). Multivariate analysis showed that female sex and higher BMI were independently associated with a reduced risk of sarcopenia (odds ratio [OR], 0.388; 95% confidence interval [CI], 0.199 to 0.755 and OR, 0.704; 95% CI, 0.618 to 0.801; all p<0.05), whereas a higher FIB- 4 was independently associated with an increased risk of sarcopenia (OR, 1.817; 95% CI, 1.180 to 2.797; p=0.007). Among patients with a BMI <25 kg/m2 (n=165), those with sarcopenia (n=54, 32.7%) had a significantly higher FIB-4 than those without (n=111, 67.3%; 1.66 vs 1.38, p=0.004). Conclusions: Sarcopenia is independently associated with fibrotic burden in patients with T2DM. Further studies should investigate whether the improvement of sarcopenia can ameliorate liver fibrosis in patients with T2DM. (Gut Liver 2020;14:626-635)

Effects of transarterial chemoembolization on regulatory T cell and its subpopulations in patients with hepatocellular carcinoma.

Abstract: Regulatory T cell (Treg) plays an essential role in regulating anti-tumor immunity. The aim of this study was to investigate the effect of transarterial chemoembolization (TACE) on Treg in hepatocellular carcinoma (HCC) patients. The frequency of peripheral blood Tregs in 27 HCC patients who underwent TACE were measured at baseline and 1 month after TACE. The frequency of peripheral blood Tregs at baseline were compared with those in 23 healthy controls. Tregs were further classified into three subpopulations [Treg (I), Treg (II), Treg (III)] based on expression levels or markers and their function. The patients were divided into two groups according to tumor response after TACE; complete response group and incomplete response group. The correlations between the frequency of Treg and clinical factors were analyzed. The frequency of Treg in HCC patients (7.52%) was significantly higher than in healthy controls (4.99%) at baseline. Regarding Treg subpopulations, the frequency of Treg (II) was significantly higher in HCC patients (2.51%) than in healthy controls (0.60%). In comparison of Treg numbers at baseline and post-TACE by tumor response, the change of Treg (III) in complete response group from baseline to post-TACE was significantly decreased (63.8 → 53.2/mm3). Patients with a high post-TACE Treg (III) (3.8 months) exhibited a significantly shorter median time to progression than those with a low post-TACE Treg (III) (11.6 months). In multivariate analyses, hypoalbuminemia (hazard ratio 3.324; 95% CI 1.098–10.063, p = 0.034) and high post-TACE Treg (III) (hazard ratio 3.080; 95% CI 1.091–8.696, p = 0.034) were significant factors for associating with progression. The frequency of Tregs in HCC patients was significantly higher than in healthy controls. In addition, patients with a high post-TACE Treg (III) exhibited a significantly lower progression-free survival rate than those with a low post-TACE Treg (III).

Natural History of Untreated HBeAg-Positive Chronic HBV Infection With Persistently Elevated HBV DNA but Normal Alanine Aminotransferase.

Abstract: OBJECTIVES Nucleos(t)ide analogues (NUCs) are not routinely recommended for patients with hepatitis B e antigen-positive chronic hepatitis B virus (HBV) infection who have persistently elevated serum HBV DNA level (>20,000 IU/mL) but normal alanine aminotransferase ( 1,000,000 IU/mL (immune-tolerant phase), which was significantly (P = 0.002) different compared with those with an intermediate serum HBV DNA level (20,000-1,000,000 IU/mL). DISCUSSION The cumulative HCC risk in the untreated pEDNA group was minimal and comparable with that of the IC group. Further studies are required to determine whether early NUC treatment, indeed, reduces the HCC risk in patients with an intermediate serum HBV DNA level.

Dose escalation in radiotherapy for incomplete transarterial chemoembolization of hepatocellular carcinoma.

Abstract: To investigate the efficacy of radiation dose escalation in patients with hepatocellular carcinoma (HCC) after incomplete transarterial chemoembolization (TACE). This study evaluated retrospective data of 323 HCC patients who received radiotherapy after incomplete TACE from 2001–2016. Radiation dose in biologically effective dose (BED) (α/β = 10) was categorized as <72 Gy (261 patients) and ≥72 Gy (62 patients). Simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) was used significantly more frequently in the high-dose group (64.5% vs. 12.9%; P < 0.001). Local failure-free rate (LFFR), progression-free rate (PFR), and toxicities were compared between the two groups. Additionally, propensity score matching was performed. Median follow-up time for patients who were alive at the time of analysis was 47 months (range 18–189 months). Median overall survival after radiotherapy was 14 months. In multivariate analysis, BED ≥72 Gy was an independent predictor of favorable LFFR (hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.14–0.72; P = 0.006) and PFR (HR 0.67; 95% CI 0.45–0.98; P = 0.04). In the propensity score-matched cohort (62 pairs), 1‑year LFFR (94% vs. 81%; P = 0.002), and 1‑year PFR (49% vs. 42%; P = 0.01) were significantly higher in the high-dose group. Treatment-related toxicities were comparable between the high-dose and low-dose groups (classic radiation-induced liver disease: 5.3% [3/57] vs. 13.8% [29/210], P = 0.08; grade 2–4 gastrointestinal bleeding: 3.2% [2/62] vs. 7.3% [19/261], P = 0.39). Radiation dose with BED ≥72 Gy improved LFFR and PFR without increasing toxicity. In radiotherapy for incomplete TACE of HCC, dose escalation using SIB-IMRT should be actively considered to improve oncologic outcome.

A tool to measure the impact of inaction toward elimination of hepatitis C: A case study in Korea.

Abstract: Background and aims Hepatitis C virus (HCV) and its sequelae present a significant source of economic and societal burden. Introduction of highly effective curative therapies has made HCV elimination attainable. The study used a predictive model to assess the clinical and economic impact of implementing national screening and treatment policies toward HCV elimination in Korea. Methods A previously validated Markov disease progression model of HCV infection was employed to analyze the clinical and economic impact of various strategies for HCV diagnosis and treatment in Korea. In this analysis, the model compared the clinical and economic outcomes of current HCV-related interventions in Korea (7,000 patients treated and 4,200 patients newly diagnosed annually, starting in 2017) to four elimination scenarios: 1) initiating sufficient diagnosis and treatment interventions to meet the World Health Organization’s GHSS elimination targets by 2030, 2) delaying initiation of interventions by one year, 3) delaying initiation of interventions by two years and 4) accelerating initiation of interventions to meet elimination targets by 2025. Modelled historical incidence of HCV was calibrated to match a viremic HCV prevalence of 0.44% in 2009. Elimination scenarios required 24,000 treatments and 34,000 newly diagnosed patients annually, starting in 2018, to reach the 2030 targets. Results Compared to current “status quo” interventions, elimination (or accelerated elimination by 2025) would avert 23,700 (27,000) incident cases of HCV, 1,300 (1,400) liver-related deaths (LRDs) and 2,900 (3,100) cases of end-stage liver disease (ESLD) over the 2017–2030 time period. Postponing interventions by one (or two) years would avert 21,100 (18,600) new HCV infections, 920 (660) LRDs and 2,000 (1,400) cases of ESLD by 2030. Following elimination or accelerated elimination strategies would save 860 million USD or 1.1 billion USD by 2030, respectively, compared to the status quo, requiring an up-front investment in prevention that decreases spending on liver-related complications and death. Conclusions By projecting the impact of interventions and tracking progress toward GHSS elimination targets using modelling, we demonstrate that Korea can prevent significant morbidity, mortality and spending on HCV. Results should serve as the backbone for policy and decision-making, demonstrating how aggressive prevention measures are designed to reduce future costs and increase the health of the public.

An observational study on long-term renal outcome in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate.

Abstract: In patients with chronic hepatitis B (CHB), long-term effects of tenofovir disoproxil fumarate (TDF) on renal function have been controversial. This study aimed to analyse the real-world long-term effects of TDF on renal function in Korean patients with CHB. We analysed a cohort of 640 treatment-naive patients with CHB who were treated with TDF between May 2012 and December 2015 at Severance Hospital, Seoul, Republic of Korea. The mean age was 48.3 years old, and 59.5% were male. The proportions of hypertension and diabetes mellitus (DM) were 11.6% and 14.2%, respectively, and that of liver cirrhosis was 20.8%. During the 5-year follow-up, using a linear mixed model, serum creatinine increased from 0.77 ± 0.01 mg/dL to 0.85 ± 0.02 mg/dL (P 60 than ≦60 years old (P = .027), and in patients with diuretic use than without diuretic use (P = .008). In multivariate analysis, the independent risk factors for eGFR decrease > 20% were baseline eGFR 60 and with diuretic use compared to those without these characteristics. Baseline eGFR < 60 mL/min/1.73 m2 and use of diuretics were independent risk factors of eGFR decline of more than 20% on TDF therapy.

Hepatocellular Carcinoma Risk According to Regimens for Eradication of Hepatitis C Virus; Interferon or Direct Acting Antivirals.

Abstract: By pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it remains controversial whether there is any difference in prognosis depending on regimens-PegIFN or DAAs. We compared the probabilities of hepatocellular carcinoma (HCC) development between patients achieving an SVR by PegIFN/ribavirin (PegIFN group, n = 603) and DAAs (DAAs group, n = 479). The DAAs group was significantly older and had a higher proportion of cirrhosis than the PegIFN group. Before adjustment, the DAAs group had a higher HCC incidence than the PegIFN group (p < 0.001). However, by multivariate analyses, the DAAs (vs. PegIFN) group was not associated with HCC risk (adjusted hazard ratio 0.968, 95% confidence interval 0.380-2.468; p = 0.946). Old age, male, higher body mass index, cirrhosis, and lower platelet count were associated with increased HCC risk (all p < 0.05). After propensity score matching (PSM), a similar HCC risk between the two groups was observed (p = 0.372). We also compared HCC incidences according to sofosbuvir (SOF)-based and SOF-free DAAs, showing a similar risk in both groups before adjustment (p = 0.478) and after PSM (p = 0.855). In conclusion, post-SVR HCC risks were comparable according to treatment regimens; PegIFN- vs. DAA-based regimens and SOF-based vs. SOF-free DAA regimens. Further studies with a longer follow-up period are required.

Appraisal of Long-Term Outcomes of Liver-Directed Concurrent Chemoradiotherapy for Hepatocellular Carcinoma with Major Portal Vein Invasion

Abstract: Backgrounds and aims Molecular-targeted agents are acceptable standards to treat advanced-stage hepatocellular carcinoma (HCC), however, their therapeutic benefit, ie, sorafenib, was significantly offset in case of major vessel invasion. Liver-directed concurrent chemo-radiotherapy (LD-CCRT) provided favorable outcomes in terms of survivals and tumor shrinkage, so, we appraised its long-term therapeutic efficacy. Patients and methods Advanced HCC patients with portal vein invasion (main trunk or the 1st order branch) were enrolled. During a 5-week radiotherapy course, concurrent hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and leucovorin was administered through an implanted port on the first and last 5 days. Four weeks after LD-CCRT, a maintenance HAIC using 5-fluorouracil and cisplatin was administered every 4 weeks. Results Among 152 patients, the objective response rates as the best response by modified Response Evaluation Criteria In Solid Tumors were 48.0% after LD-CCRT and 55.3% during subsequent HAIC maintenance. After LD-CCRT, biological responses in alpha-fetoprotein and protein induced by the absence of vitamin K or antagonist-II levels were achieved in 46.2% and 52.6%, respectively. Sixteen patients (10.5%) underwent curative resection or liver transplantation after down-staging. Median overall survival and progression-free survival were 13.5 and 6.9 months, respectively. Conclusion LD-CCRT followed by maintenance HAIC yielded favorable survival outcomes in advanced HCC patients with major portal vein invasion. Through initial tumor reduction, LD-CCRT induced down-staging with subsequent curative treatment feasible in 10.5% of patients, resulting in long-term survival. Further prospective trials are warranted to confirm these results.

Sarcopenia assessed using bioimpedance analysis is associated independently with significant liver fibrosis in patients with chronic liver diseases.

Abstract: AimSarcopenia is common in patients with advanced fibrosis or cirrhosis. We investigated the correlation between sarcopenia and other clinical variables, in particular, significant liver fibrosis in patients with chronic liver diseases (CLDs).Patients and methodsPatients with CLDs who underwent tran

Cost-effectiveness of increased screening and treatment of chronic hepatitis C in Korea

Abstract: Background: Given a hepatitis C virus (HCV) elimination goal by 2030, World Health Organization (WHO) guidelines recommend scaling up HCV screening and treatment with highly-effective direct-acting...