Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

Meta-Analysis on Efficacy and Complications of Bone Morphogenetic Protein-2 for Posterior Fusion of Cervical Spine.

OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is effective for promoting robust fusion for long-level cervical deformity and revision surgeries. However, only a few studies have reported its efficacy and complications in posterior cervical fusion (PCF). METHODS: Therefore we evaluated the efficacy and complications of rhBMP-2 application in PCF surgery by searching 3 electronic databases (PubMed, Cochrane Database, and EMBASE) for studies that evaluated the use of rhBMP-2 in PCF. Five studies (1 prospective and 4 retrospective) were included in the meta-analysis. RESULTS: The quality of each study was assessed, and data on pseudarthrosis, wound infection, neurologic, and immediate medical complications were extracted and analyzed. We found that the use of rhBMP-2 in PCF showed significant benefits in terms of pseudarthrosis and no significant increases in the risk for neurologic and immediate medical complications regardless of the dose. However, high-dose (>2.1 mg/level) rhBMP-2 was a risk factor for wound infection after PCF. CONCLUSIONS: Our meta-analysis of the currently available literature suggests that patients with PCF may benefit from BMP-2 usage without increasing the risk of complications. However, dose control and containment are important to ensure a low risk of complications.

Prevalence, incidence, and outcomes of hepatitis E virus coinfection in patients with chronic hepatitis C.

This study aimed to elucidate the anti-hepatitis E virus (HEV) immunoglobulin G (IgG) prevalence and incidence of seroconversion and seroreversion as well as its risk factors and to analyze the clinical outcomes of HEV and hepatitis C virus (HCV) coinfected patients compared to those of HCV-monoinfected patients. We prospectively enrolled 502 viremic HCV patients with paired plasma samples (at intervals of ≥ 12 months) from 5 tertiary hospitals. Anti-HEV IgG positivity was tested using the Wantai ELISA kit in all paired samples. Mean age was 58.2 ± 11.5 years old, 48.2% were male, 29.9% of patients had liver cirrhosis, and 9.4% of patients were diagnosed with hepatocellular carcinoma (HCC). The overall prevalence of anti-HEV IgG positivity at enrollment was 33.3%, with a higher prevalence in males and increasing prevalence according to the subject's age. During the 916.4 person-year, the HEV incidence rate was 0.98/100 person-years (9/335, 2.7%). Hepatic decompensation or liver-related mortality was not observed. There were six seroreversion cases among 172 anti-HEV-positive patients (1.22/100 person-years). In conclusion, approximately one-third of the adult Korean chronic HCV patients were anti-HEV IgG positive. The HEV incidence rate was 1 in 100 persons per year, without adverse hepatic outcomes or mortality.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Fate of pseudarthrosis detected 2 years after anterior cervical discectomy and fusion: results of a minimum 5-year follow-up.

BACKGROUND CONTEXT: Prior study has shown that 70% of cervical pseudarthrosis after anterior cervical discectomy and fusion (ACDF) detected at 1 year will go on to fusion by 2 year. Pseudarthrosis detected 2 years after ACDF may have different bone healing potential compared to nonunion detected 1 year after surgery. Therefore, it might have a different clinical significance. PURPOSE: To examine the radiographic and clinical prognosis of pseudarthrosis detected 2 years after ACDF with a minimum follow-up of 5 years. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENTS SAMPLE: A total of 249 patients who completed a 5-year follow-up after ACDF. OUTCOMES MEASURES: Clinical outcomes such as neck pain visual analogue scale (VAS), arm pain VAS, and neck disability index (NDI) and radiographic assessment such as X-ray, computed tomography (CT) scan. METHODS: A total of 249 patients who completed a 5-year follow-up after ACDF were retrospectively reviewed. Patients who were diagnosed with pseudarthrosis at 2 years postoperatively were included. Fusion, neck pain VAS, arm pain VAS, and NDI were assessed. The results were compared between the union group (patients who achieved union), and the nonunion group (patients with pseudarthrosis) at 5 years postoperatively. RESULTS: Among the patients who had pseudarthrosis at 2 years postoperatively, the fusion rate at 5 years was 32.6% (14/43). While the union group showed continued improvements in neck pain VAS, arm pain VAS, and NDI until 5 years, the nonunion group showed significant worsening of arm pain VAS and NDI at 5 years, with the values of neck pain VAS, arm pain VAS, and NDI being significantly worse than those of the union group at 5 years. CONCLUSION: The incidence of pseudarthrosis detected at 2 years postoperatively after ACDF was 67.4%, and it remained unfused at 5 years postoperatively. Nonunion identified 2 years after ACDF may be considered a poor prognostic factor because it has less potential to achieve fusion with further follow-up and a higher chance of worsening clinical symptoms. Therefore, the presence of fusion at the 2-year follow-up can be considered an indicator of the success of the surgery.

Inverse Propensity Score-Weighted Analysis of Entecavir and Tenofovir Disoproxil Fumarate in Patients with Chronic Hepatitis B: A Large-Scale Multicenter Study.

Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) in preventing hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients; however, it remains controversial. This study aimed to conduct comprehensive comparisons between the two antivirals. CHB patients initially treated with ETV or TDF between 2012 and 2015 at 20 referral centers in Korea were included. The primary outcome was the cumulative incidence of HCC. The secondary outcomes included death or liver transplantation, liver-related outcome, extrahepatic malignancy, development of cirrhosis, decompensation events, complete virologic response (CVR), seroconversion rate, and safety. Baseline characteristics were balanced using the inverse probability of treatment weighting (IPTW). Overall, 4210 patients were enrolled: 1019 received ETV and 3191 received TDF. During the median follow-ups of 5.6 and 5.5 years, 86 and 232 cases of HCC were confirmed in the ETV and TDF groups, respectively. There was no difference in HCC incidence between the groups both before (p = 0.36) and after IPTW was applied (p = 0.81). Although the incidence of extrahepatic malignancy was significantly higher in the ETV group than in the TDF group before weighting (p = 0.02), no difference was confirmed after IPTW (p = 0.29). The cumulative incidence rates of death or liver transplantation, liver-related outcome, new cirrhosis development, and decompensation events were also comparable in the crude population (p = 0.24-0.91) and in the IPTW-adjusted population (p = 0.39-0.80). Both groups exhibited similar rates of CVR (ETV vs. TDF: 95.1% vs. 95.8%, p = 0.38), and negative conversion of hepatitis B e antigen (41.6% vs. 37.2%, p = 0.09) or surface antigen (2.8% vs. 1.9%, p = 0.10). Compared to the ETV group, more patients in the TDF group changed initial antivirals due to side effects, including decreased kidney function (n = 17), hypophosphatemia (n = 20), and osteoporosis (n = 18). In this large-scale multicenter study, ETV and TDF demonstrated comparable effectiveness across a broad range of outcomes in patients with treatment-naïve CHB during similar follow-up periods.

Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study.

BACKGROUND/AIMS: To eliminate hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the World Health Organization (WHO) criteria in 2021, this study investigated the national core indicators representing the current status of viral hepatitis B and C in South Korea. METHODS: We analyzed the incidence, linkage-to-care, treatment, and mortality rates of HBV and HCV infection using the integrated nationwide big data of South Korea. RESULTS: According to data from 2018-2020, the incidence of acute HBV infection in South Korea was 0.71 cases per 100,000 population; tthe linkage-to-care rate was only 39.4%. Among those who need hepatitis B treatment, the treatment rate was 67.3%, which was less than 80% reported in the WHO program index. The annual liver-related mortality due to HBV was 18.85 cases per 100,000 population, exceeding the WHO target of four; the most frequent cause of death was liver cancer (54.1%). The annual incidence of newly diagnosed HCV infection was 11.9 cases per 100,000 population, which was higher than the WHO impact target of five. Among HCV-infected patients, the linkage-to-care rate was 65.5% while the treatment rate was 56.8%, which were below the targets of 90% and 80%, respectively. The liver-related annual mortality rate due to HCV infection was 2.02 cases per 100,000 population. CONCLUSION: Many of the current indicators identified in the Korean population did not satisfy the WHO criteria for validation of viral hepatitis elimination. Hence, a comprehensive national strategy should be urgently developed with continuous monitoring of the targets in South Korea.

Initial treatment response and short-term mortality of spontaneous bacterial peritonitis in cirrhotic patients with hepatocellular carcinoma.

This study aimed to investigate the initial treatment response and short-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with hepatocellular carcinoma (HCC) compared with those without HCC. A total of 245 patients with liver cirrhosis diagnosed with SBP between January 2004 and December 2020 were included. Of these, 107 (43.7%) were diagnosed with HCC. Overall, the rates of initial treatment failure, 7-day and 30-day mortality were 91 (37.1%), 42 (17.1%), and 89 (36.3%), respectively. While the baseline CTP score, MELD score, culture-positive rate, and rates of antibiotic resistance did not differ between both groups, patients with HCC had a higher rate of initial treatment failure than those without HCC patients (52.3% vs. 25.4%, P < 0.001). Similarly, 30-day mortality was also significantly higher in patients with HCC (53.3% vs. 23.2%, P < 0.001). In the multivariate analysis, HCC, renal impairment, CTP grade C, and antibiotic resistance were independent factors for initial treatment failure. Furthermore, HCC, hepatic encephalopathy, MELD score, and initial treatment failure were independent risk factors for 30-day mortality, with statistically significant poor survival outcomes in patients with HCC (P < 0.001). In conclusion, HCC is an independent risk factor for initial treatment failure and high short-term mortality in patients with cirrhosis with SBP. It has been suggested that more attentive therapeutic strategies are required to improve the prognosis of patients with HCC and SBP.

CAGE-B and SAGE-B models better predict the hepatitis B virus-related hepatocellular carcinoma after 5-year entecavir treatment than PAGE-B.

OBJECTIVES: The PAGE-B model consists of variables at the initiation of antiviral therapy (AVT), whereas the SAGE-B and CAGE-B models consist of variables after 5 years of AVT. We aimed to compare the predictive accuracy of three risk prediction models for hepatocellular carcinoma (HCC) development after 5 years of AVT in patients with chronic hepatitis B (CHB). METHODS: A total of 1335 patients who initiated entecavir (ETV) treatment between 2006 and 2011 and were followed up for more than 5 years were enrolled in the study. RESULTS: At ETV initiation, the median age was 49 years and the median score of the PAGE-B model was 14. After 5 years of ETV treatment, the median SAGE-B and CAGE-B scores were 6 and 6. During the study period, 93 (7.0%) patients developed HCC after 5-year treatment. In multivariate analysis, PAGE-B (hazard ratio [HR] 1.151, 95% confidence interval [CI] 1.087-1.219), SAGE-B (HR 1.340, 95% CI 1.228-1.463), and CAGE-B (HR 1.327, 95% CI 1.223-1.440) models independently predicted HCC development after 5 years of treatment (all P < 0.001). The high-risk groups of the three risk prediction models showed a significantly higher risk of HCC development compared to the medium- and low-risk groups (both P < 0.05). The AUROC of the SAGE-B (0.772-0.844) and CAGE-B (0.785-0.838) models was significantly higher than those of the PAGE-B model (0.696-0.745) in predicting HCC development after 5 years of treatment (both P < 0.05). CONCLUSION: The SAGE-B and CAGE-B models might be better than the PAGE-B model in predicting HCC development after 5 years of ETV treatment.

Hinged Roof Reconstruction of Anterior Iliac Crest after Harvesting Bicortical Strut Graft for Anterior Cervical Fusion.

Introduction: The strut iliac bone graft has been widely used to achieve fusion in various anterior cervical spinal surgeries but some complications often remain, such as pain and gross deformity. Considering these, we designed a new technique to restore the iliac ridge, using the outmost part of the iliac crest. We aim to assess the efficacy of our new restoration technique of the iliac ridge after harvesting strut bone graft for anterior cervical fusion. The clinical and radiological outcomes of our hinged roof method were evaluated. Technical Note: A retrospective review was conducted of 29 patients who underwent hinged roof reconstruction of the iliac ridge after harvesting a bicortical strut bone graft for anterior cervical fusion using a cervical plate system. The clinical outcome for pain and gross appearance and radiological results were evaluated. Three months after the surgery, pain at the donor site became minimal or absent in all cases. At 1 year follow-up, no patient had reported pain and palpable discomfort, such as step-off on the donor site. Final X-ray and follow-up computed tomography revealed a bony union of the reconstructed iliac ridge to both margins. Conclusions: By showing good clinical and radiological outcomes, the authors' hinged roof reconstruction of the iliac crest after harvesting strut bone graft seemed to be a simple and effective technique that can reduce complications, such as pain and deformity on the donor iliac crest.

10-year follow-up study on medical expenses and medical care use according to biological age: National Health Insurance Service Health Screening Cohort (NHIS-HealS 2002~2019).

OBJECTIVES: The world is witnessing a sharp increase in its elderly population, accelerated by longer life expectancy and lower birth rates, which in turn imposes enormous medical burden on society. Although numerous studies have predicted medical expenses based on region, gender, and chronological age (CA), any attempt has rarely been made to utilize biological age (BA)-an indicator of health and aging-to ascertain and predict factors related to medical expenses and medical care use. Thus, this study employs BA to predict factors that affect medical expenses and medical care use. MATERIALS AND METHODS: Referring to the health screening cohort database of the National Health Insurance Service (NHIS), this study targeted 276,723 adults who underwent health check-ups in 2009-2010 and kept track of the data on their medical expenses and medical care use up to 2019. The average follow-up period is 9.12 years. Twelve clinical indicators were used to measure BA, while the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses were used as the variables for medical expenses and medical care use. For statistical analysis, this study employed Pearson correlation analysis and multiple regression analysis. RESULTS: Regression analysis of the differences between corrected biological age (cBA) and CA exhibited statistically significant increases (p<0.05) in all the variables of the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses. CONCLUSIONS: This study quantified decreases in the variables for medical expenses and medical care use based on improved BA, thereby motivating people to become more health-conscious. In particular, this study is significant in that it is the first of its kind to predict medical expenses and medical care use through BA.

Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study.

BACKGROUND: Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries. AIM: To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR. METHODS: This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results. RESULTS: During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis. CONCLUSION: Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.

Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study.

BACKGROUND/AIM: Sorafenib is the first systemic therapy for the treatment of advanced-stage hepatocellular carcinoma (HCC) and progressive HCC after locoregional therapy. The aim of this study was to evaluate the prognostic factors of long-term survivors after sorafenib treatment. METHODS: This multicenter, retrospective, cohort study included 1,566 unresectable HCC patients who received sorafenib treatment between 2007 and 2014 in nine tertiary centers in Korea. The patients were classified into a long-term survivor group (survival more than two years, n = 257) or a control group (n = 1309). The primary outcomes were the prognostic factors affecting long-term survival. Secondary endpoints included time-to-progression and other safety profiles. RESULTS: The patients were predominantly men (83.8%) with chronic hepatitis B (77.3%) and Barcelona clinic of liver cancer-stage C (BCLC-C) (78.3%). The median overall survival was 9.0 months. After treatment, eight patients (0.4%) achieved complete response and 139 patients (8.8%) achieved partial response according to the mRECIST criteria. The prognostic factors predicting long-term survival were metformin use (adjusted hazard ratio [aHR] = 3.464; P < 0.001), hand-foot skin reaction (aHR = 1.688; P = 0.003), and concomitant treatment with chemoembolization or radiotherapy (aHR = 2.766; P < 0.001). Poor prognostic factors of long-term survival were a Child-Pugh score of B (HR = 0.422; P < 0.001), the presence of extrahepatic metastasis (HR = 0.639; P = 0.005), main portal vein invasion (HR = 0.502; P = 0.001), and elevated alpha-fetoprotein (>1,000 ng/mL; HR = 0.361; P < 0.001). CONCLUSION: This large, multicenter, retrospective study showed an objective response rate of 9.1% and a proportion of long-term survivors of 16.4% in Korean patients. The prognostic factors derived in our study can be used in clinical practice during sorafenib treatment.

The Superoxide Dismutase Mimetic M40403, Improves 5-Fluorouracil-induced Small Intestinal Mucositis in a Mouse Model.

BACKGROUND/AIM: Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. MATERIALS AND METHODS: BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. RESULTS: M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. CONCLUSION: M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea.

Maximal diameter of liver abscess independently predicts prolonged hospitalization and poor prognosis in patients with pyogenic liver abscess.

BACKGROUND/AIMS: This study aimed to investigate the factors associated with prolonged hospital stay and in-hospital mortality in patients with pyogenic liver abscess. METHODS: We retrospectively reviewed data from patients with pyogenic liver abscess who were admitted between 2005 and 2018 at three tertiary hospitals in Jeonbuk province, South Korea. Prolonged hospital stay was defined as a duration of hospital admission of more than 21 days. RESULTS: A total of 648 patients (406 men and 242 women) diagnosed with pyogenic liver abscess were enrolled in the study. The mean maximal diameter of the liver abscess was 5.4 ± 2.6 cm, and 74.9% of the lesions were single. The three groups were divided according to the maximal diameter of the abscess. Laboratory parameters indicated a more severe inflammatory state and higher incidence of complications and extrahepatic manifestations with increasing abscess size. Rates of percutaneous catheter drainage (PCD) insertion, multiple PCD drainage, and salvage procedures as well as duration of drainage were also higher in the large liver abscess group. Of note, the duration of hospitalization and in-hospital mortality were significantly higher in the large hepatic abscess group. A multivariate analysis revealed that underlying diabetes mellitus, hypoalbuminemia, high baseline high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and large maximal abscess diameter were independent factors associated with prolonged hospital stay. Regarding in-hospital mortality, acute kidney injury at admission and maximal diameter of the abscess were independent factors associated with in-hospital mortality. CONCLUSIONS: A large maximal diameter of the liver abscess at admission indicated prolonged hospitalization and poor prognosis. More aggressive treatment strategies with careful monitoring are warranted in patients with large liver abscesses.

Addition of liver stiffness enhances the predictive accuracy of the PAGE-B model for hepatitis B-related hepatocellular carcinoma.

BACKGROUND: The modified PAGE-B (mPAGE-B) and PAGE-B models reliably predict the risk of developing chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). AIM(S): To investigate whether the addition of liver stiffness (LS) value, assessed using transient elastography, enhanced the predictive accuracies of these models METHODS: Patients with CHB who started anti-viral therapy (AVT) between 2007 and 2017 were enrolled. The training (Yonsei University Hospital) and validation (seven Korean referral institutes) cohorts contained 1211 and 973 patients, respectively. RESULTS: Based on multivariate analysis, older age (hazard ratio [HR] = 1.051, 95% confidence interval [CI] = 1.031-1.071), male sex (HR = 2.265, 95% CI = 1.463-3.506), lower platelet count (HR = 0.993, 95% CI = 0.989-0.997) and greater LS values (HR = 1.015, 95% CI = 1.002-1.028) were independently associated with an increased risk of HCC development (all P < 0.05). Thus, we developed a modified PAGELS -B model (maximum score 34) that included age, male sex, platelet count and LS value. The integrated area under the curve of the modified PAGELS model was greater than those of the PAGE-B and mPAGE-B models (0.760 vs 0.714 and 0.716, respectively) in the derivation dataset. The cumulative HCC incidence was significantly higher in the high-risk (modified PAGE-BLS score ≥ 24) group than in the intermediate-risk (modified PAGELS -B score 12-24) or low-risk (modified PAGELS -B score < 12) group (all P < 0.001). Similar results were observed in the validation cohort. CONCLUSIONS: The predictive accuracies of the PAGE-B and mPAGE-B models were validated in Korean patients with CHB receiving AVT. However, the modified PAGELS -B model featuring the addition of LS value showed higher predictability than the PAGE-B and mPAGE-B models.

Patterns and Outcomes in Hepatocellular Carcinoma Patients with Portal Vein Invasion: A Multicenter Prospective Cohort Study.

BACKGROUND AND AIMS: Sorafenib is a proven first-line treatment recommended for hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). However, multiple treatment modalities are used in clinical practice as a first-line option. This study is a prospective, observational, multicenter, cohort study evaluating patterns of treatment modalities and outcomes for HCC patients with PVI. METHODS: The baseline characteristics, treatment modalities, and outcomes were prospectively collected for 287 newly diagnosed HCC patients with PVI between August 2015 and July 2016 from 16 sites in Korea. RESULTS: During a median 7.8 months of follow-up (range 0.3-24.6 months), mortality was observed in 123 (42.9%) patients. Decision tree analysis classified patients into five subgroups with different outcomes. The patterns of treatment were very heterogeneous, and there was no dominant treatment modality. The most commonly used treatment modality was transarterial chemoembolization (TACE) (20.2%) followed by TACE plus external beam radiation therapy (17.8%) and sorafenib (12.5%). When stratified according to the extent of PVI, sorafenib treatment showed comparable outcomes when the PVI extent was lobal or main/bilateral, yet showed worse outcomes when the PVI extent was limited to the segmental level compared to those who received treatment other than sorafenib. CONCLUSIONS: HCC patients with PVI comprise a heterogeneous population and are treated with various treatment modalities with diverse clinical outcomes in clinical practice. Subclassification of HCC patients with PVI is required to minimize heterogeneity and should be considered for the selection of treatment modalities and future clinical trials.

Dynamics of liver stiffness-based risk prediction model during antiviral therapy in patients with chronic hepatitis B.

OBJECTIVE: The liver stiffness-based risk prediction models predict hepatocellular carcinoma (HCC) development. We investigated the influence of antiviral therapy (AVT) on liver stiffness-based risk prediction model in patients with chronic hepatitis B (CHB). METHODS: Patients with CHB who initiated AVT were retrospectively recruited from 13 referral Korean institutes. The modified risk estimation for hepatocellular carcinoma in chronic hepatitis B (mREACH-B) model was selected for the analysis. RESULTS: Between 2007 and 2015, 1034 patients with CHB were recruited. The mean age of the study population (639 men and 395 women) was 46.8 years. During AVT, the mREACH-B score significantly decreased from the baseline to 3 years of AVT (mean 9.21 → 7.46, P < 0.05) and was maintained until 5 years of AVT (mean 7.23, P > 0.05). The proportion of high-risk patients (mREACH-B score ≥11) was significantly reduced from the baseline to 2 years of AVT (36.4% → 16.4%, P < 0.001) and was maintained until 5 years of AVT (12.2%, P > 0.05). The mREACH-B scores at baseline and 1 year of AVT independently predicted HCC development (hazard ratio = 1.209-1.224) (all P < 0.05). The cumulative incidence rate of HCC was significantly different at 5 years of AVT among risk groups (high vs. high-intermediate vs. low-intermediate vs. low) from baseline (4.5% vs. 3.2% vs. 1.5% vs. 0.8%) and 1 year (11.8% vs. 4.6% vs. 1.8% vs. 0.6%) (all P < 0.05, log-rank tests). CONCLUSIONS: The mREACH-B score was dynamically changed during AVT. Thus, repeated assessment of the mREACH-B score is required to predict the changing risk of HCC development in patients with CHB undergoing AVT.