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Background@#Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab. @*Methods@#A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin’s lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups. @*Results@#In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41–12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4–16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99–26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4–33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999). @*Conclusion@#Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.Trial Registration: ClinicalTrials.gov Identifier: NCT02585947
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Background/Aims@#Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. @*Methods@#This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. @*Results@#Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6–69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29–0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26–0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33–0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32–0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. @*Conclusions@#Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.
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Background@#/Aim: To evaluate the applicability of transarterial chemoembolization (TACE) treatment with doxorubicin drug-eluting beads (DEBs) in advanced hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). @*Methods@#This prospective study was approved by the institutional review board and informed consent was obtained from all participants. A total of 30 HCC patients with PVI received DEB-TACE between 2015 and 2018. The following parameters were evaluated: complications during DEB-TACE, abdominal pain, fever, and laboratory outcomes, including liver function change. Overall survival (OS), time to progression (TTP), and adverse events were also analyzed and assessed. @*Results@#DEBs measuring 100–300 μm in diameter were loaded with doxorubicin (150 mg per procedure). There were no complications during DEB-TACE and no significant differences in the levels of prothrombin time, serum albumin, or total bilirubin at follow-up compared to baseline. The median TTP was 102 days (95% confidence interval [CI], 42–207 days) and the median OS was 216 days (95% CI, 160–336 days). Three patients (10%) had severe adverse reactions, including transient acute cholangitis (n=1), cerebellar infarction (n=1), and pulmonary embolism (n=1), but no treatment-related death occurred. @*Conclusions@#DEB-TACE may be a therapeutic option for advanced HCC patients with PVI.
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Treatment options for advanced hepatocellular carcinoma (HCC) have been rapidly evolving. Herein, we describe a patient with advanced HCC and portal vein tumor thrombosis (PVTT) who responded decisively to a multidisciplinary approach. The patient had an ill-defined infiltrative HCC (diffuse subtype), with several intrahepatic metastasis and tumor invasion of left portal vein. Concurrent use of transarterial radioembolization (TARE) and systemic therapeutics (atezolizumab + bevacizumab) ultimately proved successful. There was marked reduction in tumor volume after TARE and an additional three cycles of atezolizumab plus bevacizumab. This concurrent treatment was well tolerated, without adverse events during immunotherapy. The impressive results achieved suggest that concurrent TARE and combination atezolizumab/bevacizumab is a promising treatment approach for advanced HCC with PVTT.
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Viral hepatitis is the most important cause of acute and chronic liver disease in Korea.Particularly, hepatitis B virus (HBV) is the leading cause of liver-related mortality. Because of the nationwide vaccinations in the 1980s, hepatitis B surface antigen positive rates substantially decreased from 8% to 3%. Moreover, the introduction of potent nucleoside or nucleotide analogs led to the effective treatment of patients who had already been infected by HBV. The remaining issue has been to develop novel drugs that can cure HBV infection.Hepatitis C virus (HCV), on the other hand, is a hepatotropic virus that is parenterally transmitted. In Korea, the prevalence of HCV is estimated to be approximately 1%. Although no effective vaccine for HCV has been developed yet, highly effective and safe direct-acting antiviral therapy, which has a short treatment duration of 8 – 12 weeks, has made HCV eradication possible globally. Currently, the unsolved issue regarding HCV management is low disease awareness among patients and health care providers. Therefore, nationwide testing for anti-HCV would be a solution to identify patients infected with HCV but with no symptoms. Lastly, the Hepatitis A virus (HAV) is orally transmitted and results in acute hepatitis. In Korea, the young adult population is a high-risk group since this group is not vaccinated against HAV. More active vaccination and improved hygiene would be necessary to prevent HAV infection.
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Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.
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Viral hepatitis is the most important cause of acute and chronic liver disease in Korea.Particularly, hepatitis B virus (HBV) is the leading cause of liver-related mortality. Because of the nationwide vaccinations in the 1980s, hepatitis B surface antigen positive rates substantially decreased from 8% to 3%. Moreover, the introduction of potent nucleoside or nucleotide analogs led to the effective treatment of patients who had already been infected by HBV. The remaining issue has been to develop novel drugs that can cure HBV infection.Hepatitis C virus (HCV), on the other hand, is a hepatotropic virus that is parenterally transmitted. In Korea, the prevalence of HCV is estimated to be approximately 1%. Although no effective vaccine for HCV has been developed yet, highly effective and safe direct-acting antiviral therapy, which has a short treatment duration of 8 – 12 weeks, has made HCV eradication possible globally. Currently, the unsolved issue regarding HCV management is low disease awareness among patients and health care providers. Therefore, nationwide testing for anti-HCV would be a solution to identify patients infected with HCV but with no symptoms. Lastly, the Hepatitis A virus (HAV) is orally transmitted and results in acute hepatitis. In Korea, the young adult population is a high-risk group since this group is not vaccinated against HAV. More active vaccination and improved hygiene would be necessary to prevent HAV infection.
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Objective@#This study aimed to prospectively compare the efficacy, safety, and mid-term outcomes of dual-switching monopolar (DSM) radiofrequency ablation (RFA) to those of conventional single-switching monopolar (SSM) RFA in the treatment of hepatocellular carcinoma (HCC). @*Materials and Methods@#This single-center, two-arm, parallel-group, randomized controlled study was approved by the Institutional Review Board. Written informed consent was obtained from all patients upon enrollment. A total of 80 patients with 94 HCC nodules were randomized into either the DSM-RFA group or SSM-RFA group in a 1:1 ratio, using a blocked randomization method (block size 2). The primary endpoint was the minimum diameter of the ablation zone per unit time.The secondary endpoints included other technical parameters, complication rate, technique efficacy, and 2-year clinical outcomes. @*Results@#Significantly higher ablation energy per unit time was delivered to the DSM-RFA group than to the SSM-RFA group (1.7 ± 0.2 kcal/min vs. 1.2 ± 0.3 kcal/min; p< 0.001). However, no significant differences were observed between the two groups for the analyzed variables, including primary endpoint, regarding size of the ablation zone and ablation time. Major complication rates were 4.9% in the DSM-RFA group and 2.6% in the SSM-RFA group (p = 1.000). The 2-year local tumor progression (LTP) rates of the HCC nodules treated using DSM-RFA and SSM-RFA were 8.5% and 4.7%, respectively (p = 0.316).The 2-year LTP-free survival rates of patients in the DSM-RFA and SSM-RFA groups were 90.0% and 94.4%, respectively (p = 0.331), and the 2-year recurrence-free survival rates were 54.9% and 75.7%, respectively (p = 0.265). @*Conclusion@#Although DSM-RFA using a separable clustered electrode delivers higher ablation energy than SSM-RFA, its effectiveness failed to show superiority over SSM-RFA in the treatment of HCC.
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Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.
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Objective@#This study aimed to compare the efficacy between no-touch (NT) radiofrequency ablation (RFA) and conventional RFA using twin internally cooled wet (TICW) electrodes in the bipolar mode for the treatment of small hepatocellular carcinomas (HCC). @*Materials and Methods@#In this single-center, two-arm, parallel-group, prospective randomized controlled study, we performed a 1:1 random allocation of eligible patients with HCCs to receive NT-RFA or conventional RFA between October 2016 and September 2018. The primary endpoint was the cumulative local tumor progression (LTP) rate after RFA. Secondary endpoints included technical conversion rates of NT-RFA, intrahepatic distance recurrence, extrahepatic metastasis, technical parameters, technical efficacy, and rates of complications. Cumulative LTP rates were analyzed using Kaplan-Meier analysis and the Cox proportional hazard regression model. Considering conversion cases from NT-RFA to conventional RFA, intentionto-treat and as-treated analyses were performed. @*Results@#Enrolled patients were randomly assigned to the NT-RFA group (37 patients with 38 HCCs) or the conventional RFA group (36 patients with 38 HCCs). Among the NT-RFA group patients, conversion to conventional RFA occurred in four patients (10.8%, 4/37). According to intention-to-treat analysis, both 1- and 3-year cumulative LTP rates were 5.6%, in the NT-RFA group, and they were 11.8% and 21.3%, respectively, in the conventional RFA group (p = 0.073, log-rank). In the as-treated analysis, LTP rates at 1 year and 3 years were 0% and 0%, respectively, in the NT-RFA group sand 15.6% and 24.5%, respectively, in the conventional RFA group (p = 0.004, log-rank). In as-treated analysis using multivariable Cox regression analysis, RFA type was the only significant predictive factor for LTP (hazard ratio = 0.061 with conventional RFA as the reference, 95% confidence interval = 0.000–0.497; p = 0.004). There were no significant differences in the procedure characteristics between the two groups. No procedure-related deaths or major complications were observed. @*Conclusion@#NT-RFA using TICW electrodes in bipolar mode demonstrated significantly lower cumulative LTP rates than conventional RFA for small HCCs, which warrants a larger study for further confirmation.
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Use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) has been partially successful. However, most HCC patients do not respond to immunotherapy. HCC has been shown to induce several immune suppressor mechanisms in patients. These suppressor mechanisms include involvement of myeloid-derived suppressor cells, regulatory T-cells, functionally impaired dendritic cells (DCs), neutrophils, monocytes, and tumor associated macrophages. The accumulation of immunosuppressive cells may lead to an immunosuppressive tumor microenvironment as well as the dense fibrotic stroma which may contribute to immune tolerance. Our laboratory has been investigating different cellular mechanisms of immune suppression in HCC patients. In vitro as well as in vivo studies have demonstrated that abrogation of the suppressor cells enhances or unmasks tumor-specific antitumor immune responses. Two or three effective systemic therapies including ICIs and/or molecular targeted therapies and the addition of innovative combination therapies targeting immune suppressor cells may lead to increased immune recognition with a greater tumor response. We reviewed the literature for the latest research on immune suppressor cells in HCC, and here we provide a comprehensive summary of the recent studies in this field.
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Background/Aims@#The risk for colonoscopic postpolypec-tomy bleeding (PPB) in patients with chronic liver disease (CLD) remains unclear. We determined the incidence and risk factors for colonoscopic PPB in patients with CLD, espe-cially those with liver cirrhosis. @*Methods@#We retrospectively reviewed the medical records of patients with CLD who un-derwent colonoscopic polypectomy at Seoul National Univer-sity Hospital between 2011 and 2014. The study endpoints were immediate and delayed PPB. @*Results@#A total of 1,267 consecutive patients with CLD were included in the study. Im-mediate PPB occurred significantly more often in the ChildPugh (CP) B or C cirrhosis group (17.5%) than in the CP-A (6.3%) and chronic hepatitis (4.6%) groups (p10 mm in size (p=0.010). @*Conclusions@#Patients with CP-B or C cirrhosis had an increased risk for bleeding fol-lowing colonoscopic polypectomy.
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Background/Aims@#Patients with an intermediate stage of hepatocellular carcinoma (HCC) represent a highly heterogeneous population; therefore, many models have been proposed to predict the survival of these patients. The aim of this study was to evaluate the prognostic performance of a novel subclassification for tumors classified as Barcelona Clinic Liver Cancer (BCLC) stage B using the Model to Estimate Survival in Ambulatory HCC patients (MESIAH). @*Methods@#This analysis was based on 377 patients with HCC treated at Seoul National University Hospital (training cohort) and 189 patients at the Soonchunhyang University Bucheon Hospital (validation cohort). Four subclassification systems were tested: MESIAH; original BCLC B subclassification (B1, B2, B3, and B4); modified model A (B1, B2, and B3+B4); and modified model B (B1, B2+B3, and B4). @*Results@#Median survival progressively decreased from stage B1 through stages B2 to B3 according to the new MESIAH subclassification (p<0.001). Moreover, significantly different survival among contiguous stages was observed. In the multivariable Cox regression, the MESIAH subclassification was an independent predictor of overall survival (p<0.001). In terms of discrimination and calibration, MESIAH performed better than the original BCLC B subclassification, modified model A and modified model B. @*Conclusions@#The MESIAH model would be an effective tool for stratifying heterogeneous BCLC stage B cancer, and the ability of this model to predict survival is better than that of the other previously proposed models.
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Background/Aims@#Renal toxicity is a concern in patients with chronic hepatitis B taking nucleotide analogues, such as adefovir (ADV) and tenofovir disoproxil fumarate (TDF). We sought to determine the long-term renal effects of nucleotide analogue treatment versus entecavir (ETV) treatment. @*Methods@#In this retrospective single-center study, we selected 87 patients who were treated with ADV and subsequently with TDF from June 2008 to December 2013. ETV-treated patients were matched by treatment duration. We analyzed the creatinine increase over 0.5 mg/dL, glomerular filtration rate (GFR) decrease over 25%, phosphorus decrease under 2.0 mg/dL, and dose reduction of antiviral agents. @*Results@#The median follow-up period was 60.0 months for both groups. The incidence of liver cirrhosis was higher in the ADVTDF group than in the ETV group (32.2% vs 74.7%, p<0.01).Creatinine increased in both groups during follow-up, but the difference was not significant (5.7% and 2.3%, p=0.44). In addition, GFR decreased more often in the ADV-TDF group than in the ETV group (31.0% and 14.9%, p=0.01). After multivariate Cox regression analysis, ADV-TDF treatment was significantly associated with a GFR decrease over 25% (hazard ratio, 2.10; 95% confidence interval, 1.08 to 4.10; p=0.03) after adjusting for the baseline GFR decrease. @*Conclusions@#Patients taking nucleotide analogues had a significantly higher number of renal events than did those taking ETV. Clinicians should be aware of the development of renal toxicity in this patient population. Further long-term studies are warranted.
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Background/Aims@#Prognostic models are lacking for patients with recurrent hepatocellular carcinoma (HCC) following surgical resection. This study devised and validated a new hepatoma arterial-embolization prognostic (HAP) score optimized for use in patients undergoing treatment with transarterial chemoembolization (TACE) for recurrence subsequent to surgical resection of HCC. @*Methods@#Training cohort (n=424) and validation cohort (n=350) patients with recurrent HCC after resection treated with TACE between 2003 and 2016 were enrolled. Cox regression and area under the receiver operating characteristic curve (AUC) analyses were used to identify risk factors for survival and to calculate the predictive performance of risk scores, respectively. @*Results@#The median age of the study population was 59.2 years. α-Fetoprotein >400 ng/mL (hazard ratio [HR]=1.815), serum albumin ≤3.5 g/dL (HR=1.966), tumor number ≥2 (HR=1.425), tumor size >5 cm at resection or recurrence (HR=1.356), segmental portal vein invasion at resection or recurrence (HR=2.032), and time from resection to recurrence ≤1 years (HR=1.849) independently predicted survival (all p<0.05). The postoperative HAP (pHAP) model based on the rounded HRs of these variables showed an AUC of 0.723 for predicting survival at 3 years, which was significantly higher than AUCs of other HAP-based models, including HAP, modified HAP, and modified HAP-II scores (0.578-0.621) (all p<0.05). The accuracy of pHAP was maintained in the entire cohort (n=774; AUC=0.776 at 3 years). @*Conclusions@#A new pHAP score optimized for patients treated with TACE due to recurrent HCC after resection showed acceptable accuracy and was externally validated. Further studies of means by which to select treatment options other than TACE for high-risk patients according to pHAP scores are warranted.
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Background/Aims@#Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis due to the lack of effective systemic therapies. Epithelial-to-mesenchymal transition (EMT) is a pivotal event in tumor progression, during which cancer cells acquire invasive properties. In this study, we investigated the effects of phosphatidylinositol 3-kinase (PI3K) inhibitors, including LY294002 and idelalisib, on the EMT features of HCC cells in vitro. @*Methods@#Human HCC cell lines, including Huh-BAT and HepG2, were used in this study. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and cell cycle distributions were evaluated using a flow cytometer by propidium iodide staining. Immunofluorescence staining, quantitative real-time polymerase chain reaction, and immunoblotting were performed to detect EMT-associated changes. @*Results@#PI3K inhibitors suppressed the proliferation and invasion of HCC cells and deregulated the expression of EMT markers, as indicated by increased expression of E-cadherin, an epithelial marker, and decreased expression of N-cadherin, a mesenchymal marker, and Snail, a transcription factor implicated in EMT regulation. Furthermore, LY294002 and idelalisib inhibited the phosphorylation of GSK-3β and induced the nuclear translocation of GSK-3β, which corresponded to the downregulation of Snail and β-catenin expressions in Huh-BAT and HepG2 cells. @*Conclusions@#The inhibition of PI3K/Akt signaling decreases Snail expression by enhancing the nuclear translocation of GSK-3β, which suppresses EMT in HCC cells, suggesting the potential clinical application of PI3K inhibitors for HCC treatment.
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Background/Aims@#Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients. @*Methods@#Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias. @*Results@#Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0–10.8) months for regorafenib and 5.9 (95% CI, 3.7–8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30–0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51–1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04). @*Conclusions@#After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.
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Objective@#The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. @*Materials and Methods@#We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. @*Results@#Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. @*Conclusion@#The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.
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Objective@#The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. @*Materials and Methods@#We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. @*Results@#Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. @*Conclusion@#The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.
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BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) is potentially nephrotoxic in chronic hepatitis B patients. Hepatocellular carcinoma (HCC) patients treated using transarterial chemoembolization (TACE) are at an increased risk of renal injury. The aim of this study was to determine whether TDF is associated with more renal adverse events than entecavir (ETV) in HCC patients treated with TACE. METHODS: In this retrospective single-center study, we selected 53 HCC patients who were treated with TDF from January 2012 to July 2013 and had their first TACE procedure in the same period. These patients were matched by age and sex to patients treated with ETV. RESULTS: There were no significant differences in baseline characteristics, including HCC factors, and nephrotoxic drug use, between the two groups. The median follow-up period was 17.0 and 20.0 months for the TDF and ETV groups, respectively. There was no difference during the follow-up period between the TDF and ETV groups in the increase in creatinine over 0.5 mg/dL (17.0% and 17.0%, P=1.00, respectively) and the decrease in eGFR over 25% (43.4% and 41.5%, P=0.84, respectively). Multivariate analysis revealed that Child-Pugh class over B (hazard ratio [HR], 7.30; 95% confidence interval [CI] 2.79–19.10; P<0.01) was associated with increase in creatinine, and Child-Pugh class over B (HR, 82.74; 95% CI 12.31–555.83; P<0.01) and Barcelona-Clinic Liver Cancer stage over B (HR, 14.93; 95% CI 1.60–139.51; P=0.02) were associated with decrease in eGFR. CONCLUSIONS: TDF has comparable safety to that of ETV for HCC patients undergoing TACE.