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Background/Aims@#Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). @*Methods@#We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. @*Results@#Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353–5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484– 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). @*Conclusions@#Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.
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Background/Aims@#Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB).However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. @*Methods@#We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. @*Results@#A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (–0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. @*Conclusions@#BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.
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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. @*Conclusions@#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.
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Background/Aims@#We investigated the factors related to spleen length and the diagnostic accuracy of a model using spleen length corrected by related factors, for the prediction of varices needing treatment (VNT). @*Methods@#Various prediction models for VNT including spleen length were analyzed in the cohort of compensated advanced chronic liver disease (cACLD), defined as liver stiffness (LS) ≥10 kPa in a recent study. The associated factors for spleen length were identified in healthy subjects to improve the prediction of VNT. @*Results@#Among 1,218 cACLD patients, VNT was noted in 249 patients (20.4%). On multivariate analysis, longer spleen length, lower platelet count, and higher LS value were independent predictors for VNT (all p<0.001). In multivariate analysis of 1,041 healthy subjects, age (β=–0.027), sex (β=0.762), and body mass index (β=0.097) were found to be significant factors for spleen length (all p<0.001). Using the β values, the estimated spleen length was calculated. To improve the prediction of VNT, the ratio of measured and estimated spleen length was calculated. Based on binary regression analysis results, the LS value-spleen ratio to platelet score (LSRPS) was calcu-lated as follows: 0.027×LS value (kPa)+2.690×measured/estimated spleen ratio–0.011×platelet count (cells×10 9 /L)–4.215. The area under the receiver operating characteristic of the LSRPS for VNT was 0.820, which was significantly higher than 0.797 of LS value-spleen diameter to plateletratio score (LSPS) (p=0.006). @*Conclusions@#Spleen length is influenced by age, sex, and body mass index in the Asian population. The LSRPS using the measured/estimated spleen ratio had higher diagnostic accuracy than LSPS in predicting VNT in patients with cACLD.
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Background@#/Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. @*Methods@#This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. @*Results@#In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. @*Conclusions@#This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.
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Background@#Several studies have recently suggested that liver disease and cirrhosis were risk factors for poor outcomes in patients with coronavirus disease 2019 (COVID-19) infections.However, no large data study has reported the clinical course of COVID-19 patients with chronic hepatitis B virus (HBV) infections. This study investigated whether HBV infection had negative impacts on the clinical outcomes of COVID-19 patients. @*Methods@#We performed a nationwide population-based cohort study with 19,160 COVID-19-infected patients in 2020 from the Korean Health Insurance Review and Assessment database. The clinical outcomes of COVID-19 patients with chronic HBV infections were assessed and compared to those of non-HBV-infected patients. @*Results@#Of the 19,160 patients diagnosed with COVID-19, 675 (3.5%) patients had chronic HBV infections. The HBV-infected patients were older and had more commodities than the non-HBV infected COVID-19 patients. During the observation period, COVID-19-related mortality was seen in 1,524 (8.2%) of the non-HBV-infected 18,485 patients, whereas 91 (13.5%) in HBV-infected 675 patients died of COVID-19 infection. Compared to patients without HBV infections, a higher proportion of patients with chronic HBV infections required intensive care unit (ICU) admission and had organ failures. However, odds ratios for mortality, ICU admission, and organ failure were comparable between the two groups after adjusting for age, sex, and comorbid diseases including liver cirrhosis and hepatocellular carcinoma. @*Conclusion@#COVID-19-infected patients with HBV infections showed worse clinical courses than non-HBV-infected COVID-19 patients. However, after adjustment, chronic HBV infection itself does not seem to affect the clinical outcomes in COVID-19 patients.
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Background/Aims@#Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. @*Methods@#The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. @*Results@#The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. @*Conclusions@#The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.
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Background/Aims@#Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. @*Methods@#Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). @*Results@#Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). @*Conclusions@#HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.
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Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
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Background/Aims@#Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome. @*Methods@#Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline. @*Results@#A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05). @*Conclusions@#Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.
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Background/Aims@#Most prognostic prediction models for patients with liver cirrhosis include serum total bilirubin (TB) level as a component. This study investigated prognostic performance of serum direct bilirubin (DB) and developed new DB level-based prediction models for cirrhosis. @*Methods@#A total of 983 hospitalized patients with liver cirrhosis were included. DB-Model for End-Stage Liver Disease (MELD) score was calculated using MELD score formula, with serum DB level replacing TB level. @*Results@#Mean age of study population was 56.1 years. Alcoholic liver disease was the most frequent underlying condition (471 patients, 47.9%). Within 6 months, 144 patients (14.6%) died or received liver transplantation due to severe liver dysfunction. The area under the receiver operating characteristic curve (AUROC) for prediction of 6-month mortality with DB level was significantly higher than that with TB level (p<0.001). The AUROC of DB-MELD score for prediction of 6-month mortality was significantly higher than that of MELD score (p<0.001). Patients were randomly divided into training (n=492) and validation (n=491) cohorts. A new prognostic prediction model, “Direct Bilirubin, INR, and Creatinine” (DiBIC) score, was developed based on the most significant predictors of 6-month mortality. In training set, AUROC of DiBIC score for prediction of 6-month mortality was 0.892, which was significantly higher than that of the MELD score (0.875, p=0.017), but not different from that of DB-MELD score (0.886, p=0.272). Similar results were observed in validation set. @*Conclusions@#New prognostic models, DB-MELD and DiBIC scores, have good prognostic performance in liver cirrhosis patients, outperforming other currently available models.
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Background/Aims@#The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. @*Methods@#A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. @*Results@#After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. @*Conclusions@#PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.
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Background/Aims@#We investigated changes in recurrence rates and significant recurrence predictors over time after complete cure of hepatocellular carcinoma (HCC). @*Methods@#A total of 1,491 patients with first-time diagnosis of Barcelona Clinic Liver Cancer stage A HCC, completely cured by treatment between 2007 and 2016, were recruited from two Korean tertiary institutes. @*Results@#The mean age of the population (1,144 men and 347 women) was 58.6 years. Of the total population, 914 patients (61.3%) had liver cirrhosis. Nine-hundred and forty-one (63.1%) and 550 (36.9%) patients were treated with surgical resection and radiofrequency ablation (RFA), respectively. One-year cumulative incidences of HCC recurrence were 14.3%, 9.9%, and 5.1% from the time of treatment, 3 years after treatment, and 5 years after treatment, respectively. Upon multivariate analysis, multiple tumors, maximal tumor size ≥3 cm, and high Model for End-Stage Liver Disease scores were independently associated with increased HCC recurrence risk from the time of treatment and 1 and 2 years after curative treatment (all p<0.05, except for maxi-mal tumor size ≥3 cm for recurrence 2 years after treatment). Meanwhile, liver cirrhosis and RFA were independently associated with the increased HCC recurrence risk for almost all time points (liver cirrhosis: all p<0.05; RFA: all p<0.005 except for recurrence from 5 years after treatment). @*Conclusions@#The recurrence rate of HCC after curative treatment gradually decreased over time. Two years after treatment, when tumor-related factors lose their prognostic implications, may be used as a cutoff to define the boundary between early and late recurrence of HCC.
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A 60-year-old man diagnosed with unresectable hepatocellular carcinoma (HCC) presented to the hospital with pain in the perineal region. He had been taking lenvatinib every day for 2 months after he was diagnosed with HCC with metastases to the lymph node, small bowel mesentery, and retroperitoneal space. Enhanced abdominal computed tomography revealed mild elevation in intensity in the perineal subcutaneous tissue with subcutaneous emphysema. The patient was diagnosed with Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV with full-thickness skin loss and tissue necrosis in the muscular layer. The patient was taken off the medication with prescription of antibiotics, and after 3 weeks, the skin has fully recovered. This is the first report of an HCC patient who presented with a skin ulceration of stage IV after lenvatinib treatment. We recommend stopping the medication immediately and changing to alternative treatments with appropriate supportive care.
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Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
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Background/Aims@#Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome. @*Methods@#Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline. @*Results@#A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05). @*Conclusions@#Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.
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Background/Aims@#Most prognostic prediction models for patients with liver cirrhosis include serum total bilirubin (TB) level as a component. This study investigated prognostic performance of serum direct bilirubin (DB) and developed new DB level-based prediction models for cirrhosis. @*Methods@#A total of 983 hospitalized patients with liver cirrhosis were included. DB-Model for End-Stage Liver Disease (MELD) score was calculated using MELD score formula, with serum DB level replacing TB level. @*Results@#Mean age of study population was 56.1 years. Alcoholic liver disease was the most frequent underlying condition (471 patients, 47.9%). Within 6 months, 144 patients (14.6%) died or received liver transplantation due to severe liver dysfunction. The area under the receiver operating characteristic curve (AUROC) for prediction of 6-month mortality with DB level was significantly higher than that with TB level (p<0.001). The AUROC of DB-MELD score for prediction of 6-month mortality was significantly higher than that of MELD score (p<0.001). Patients were randomly divided into training (n=492) and validation (n=491) cohorts. A new prognostic prediction model, “Direct Bilirubin, INR, and Creatinine” (DiBIC) score, was developed based on the most significant predictors of 6-month mortality. In training set, AUROC of DiBIC score for prediction of 6-month mortality was 0.892, which was significantly higher than that of the MELD score (0.875, p=0.017), but not different from that of DB-MELD score (0.886, p=0.272). Similar results were observed in validation set. @*Conclusions@#New prognostic models, DB-MELD and DiBIC scores, have good prognostic performance in liver cirrhosis patients, outperforming other currently available models.
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Background/Aims@#The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. @*Methods@#A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. @*Results@#After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. @*Conclusions@#PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.
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Background/Aims@#We investigated changes in recurrence rates and significant recurrence predictors over time after complete cure of hepatocellular carcinoma (HCC). @*Methods@#A total of 1,491 patients with first-time diagnosis of Barcelona Clinic Liver Cancer stage A HCC, completely cured by treatment between 2007 and 2016, were recruited from two Korean tertiary institutes. @*Results@#The mean age of the population (1,144 men and 347 women) was 58.6 years. Of the total population, 914 patients (61.3%) had liver cirrhosis. Nine-hundred and forty-one (63.1%) and 550 (36.9%) patients were treated with surgical resection and radiofrequency ablation (RFA), respectively. One-year cumulative incidences of HCC recurrence were 14.3%, 9.9%, and 5.1% from the time of treatment, 3 years after treatment, and 5 years after treatment, respectively. Upon multivariate analysis, multiple tumors, maximal tumor size ≥3 cm, and high Model for End-Stage Liver Disease scores were independently associated with increased HCC recurrence risk from the time of treatment and 1 and 2 years after curative treatment (all p<0.05, except for maxi-mal tumor size ≥3 cm for recurrence 2 years after treatment). Meanwhile, liver cirrhosis and RFA were independently associated with the increased HCC recurrence risk for almost all time points (liver cirrhosis: all p<0.05; RFA: all p<0.005 except for recurrence from 5 years after treatment). @*Conclusions@#The recurrence rate of HCC after curative treatment gradually decreased over time. Two years after treatment, when tumor-related factors lose their prognostic implications, may be used as a cutoff to define the boundary between early and late recurrence of HCC.
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A 60-year-old man diagnosed with unresectable hepatocellular carcinoma (HCC) presented to the hospital with pain in the perineal region. He had been taking lenvatinib every day for 2 months after he was diagnosed with HCC with metastases to the lymph node, small bowel mesentery, and retroperitoneal space. Enhanced abdominal computed tomography revealed mild elevation in intensity in the perineal subcutaneous tissue with subcutaneous emphysema. The patient was diagnosed with Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV with full-thickness skin loss and tissue necrosis in the muscular layer. The patient was taken off the medication with prescription of antibiotics, and after 3 weeks, the skin has fully recovered. This is the first report of an HCC patient who presented with a skin ulceration of stage IV after lenvatinib treatment. We recommend stopping the medication immediately and changing to alternative treatments with appropriate supportive care.