Yun Bin Lee

CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis

Accurate prognostication of acute‐on‐chronic liver failure (ACLF) is essential for therapeutic decisions. Our aim was to validate a novel scoring system for predicting mortality, the chronic liver failure‐sequential organ failure assessment (CLIF‐SOFA), in a population of Asian patients with ACLF.

Efficacy of Entecavir-Tenofovir Combination Therapy for Chronic Hepatitis B Patients with Multidrug-Resistant Strains

ABSTRACT The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.

Prior exposure to lamivudine increases entecavir-resistance risk in chronic hepatitis B patients without detectable lamivudine-resistance

ABSTRACT The efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1, n = 142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2, n = 233), and patients with LAM-R when starting ETV (group 3, n = 125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR] = 14.4, P < 0.001) but also in group 2 (HR = 5.0, P < 0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR = 13.0, P = 0.013) as well as group 3 (HR = 43.9, P < 0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.

Serum Insulin-like Growth Factor-I Level Is an Independent Predictor of Recurrence and Survival in Early Hepatocellular Carcinoma: A Prospective Cohort Study

Purpose: Insulin-like growth factor-I (IGF-I) reflects hepatic synthetic function and plays an important role in the development and progression of various cancers. In this study, we investigated whether pretreatment serum IGF-I levels predict time-to-recurrence (TTR) and overall survival (OS) in patients with early-stage hepatocellular carcinoma after curative treatment. Experimental Design: Consecutive patients with hepatocellular carcinoma who had undergone surgical resection, radiofrequency ablation, or percutaneous ethanol injection as curative treatments of early hepatocellular carcinoma were included from two prospective cohorts and the training set (n = 101) and the validation set (n = 91) were established. Serum samples were collected before treatment and the levels of IGF-I and IGF-binding protein-3 (IGFBP-3) were analyzed with regard to their associations with recurrence and survival. Results: In the training set, patients with low IGF-I levels showed significantly shorter TTR [median, 14.6 months; 95% confidence interval (CI), 1.8–27.5] than patients with high IGF-I levels (median, 50.8 months; 95% CI, 36.9–64.7; P < 0.001) during a median follow-up period of 52.4 months. In the multivariate analysis, low levels of IGF-I were an independent predictor of recurrence (HR, 2.49; 95% CI, 1.52–4.08; P < 0.001). Furthermore, together with high-serum α-fetoprotein and multiple tumors, low levels of IGF-I remained an independent predictor of poorer survival (HR, 8.00; 95% CI, 1.94–33.01; P = 0.004). Applied to the independent validation set, low-serum IGF-I levels maintained their prognostic value for shorter TTR and OS. Conclusions: Low-baseline IGF-I levels independently correlated with shorter TTR and poorer survival in patients with early-stage hepatocellular carcinoma after curative treatment. Clin Cancer Res; 19(15); 4218–27. ©2013 AACR.

Comparison of Transarterial Chemoembolization and Hepatic Resection for Large Solitary Hepatocellular Carcinoma: A Propensity Score Analysis

PURPOSE To compare long-term survival after hepatic resection and transarterial chemoembolization of large solitary hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Analysis of 91 and 68 consecutive patients with large (≥ 5 cm) solitary HCCs who underwent hepatic resection and transarterial chemoembolization, respectively, was performed. Overall survival and time to progression (TTP) were estimated using the Kaplan-Meier method and compared using the Cox proportional hazards model. To control for treatment-selection bias, matched groups of patients were selected using a propensity score matching method, and survival analysis was repeated. RESULTS During the follow-up period (median, 60.7 mo; range, 0.5-122.2 mo), 42 (46%) patients in the hepatic resection group and 35 (51%) patients in the transarterial chemoembolization group died. The 1-year, 3-year, and 5-year overall survival rates of the hepatic resection and transarterial chemoembolization groups were 91.1%, 80.0%, and 66.4% (hepatic resection group) and 89.8%, 72.8%, and 49.6% (transarterial chemoembolization group) (P = .023). TTP was significantly longer in patients who underwent hepatic resection (P < .001). Hepatitis B surface antigen positivity and the absence of portal hypertension were independent predictors for favorable overall survival. For patients with platelet counts ≤ 100,000/mm(3), Child-Pugh score of 6, smaller HCCs (≤ 7 cm), or portal hypertension, hepatic resection and transarterial chemoembolization yielded similar overall survival rates. After propensity score matching, transarterial chemoembolization was comparable to hepatic resection in overall survival (P = .293), whereas TTP remained longer in patients who underwent hepatic resection (P = .001). CONCLUSIONS Transarterial chemoembolization can lead to results comparable to hepatic resection in the treatment of large solitary HCCs, particularly in patients with clinically presumed portal hypertension.

Tenofovir Monotherapy versus Tenofovir plus Lamivudine or Telbivudine Combination Therapy in Treatment of Lamivudine-Resistant Chronic Hepatitis B

ABSTRACT Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P = 0.562 and P = 0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.

Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.

Rifaximin might decrease the risk of portal hypertension‐related complications by controlling small intestinal bacterial overgrowth.

Efficacy of Adefovir-Based Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B Virus Infection

ABSTRACT Treatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB) patients are not yet well established. The aim of this study was to evaluate overall antiviral efficacy and to compare the efficacy of combination therapy with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus (HBV) variants. Virologic, biochemical, and serologic responses during combination therapy with ADV plus nucleoside analogues were assessed. Propensity score analysis was used to select a matched group of patients for the comparison of rescue therapy regimens. A total of 67 consecutive patients were analyzed. Complete virologic suppression was achieved in 27 patients. The overall cumulative incidence of complete virologic suppression at month 24 was 47.4%: 44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV. There was no significant difference between these two groups (P = 0.234). The cumulative incidences of complete virologic suppression were still comparable between the two groups selected and matched using the propensity score model (P = 0.419). Virologic breakthrough was observed in 9 patients, and rtA181V substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg) negativity and lower baseline HBV DNA level were associated with complete virologic suppression in univariate analysis. In multivariate analysis, lower baseline HBV DNA level remained an independent predictor. In conclusion, combination therapy with ADV plus nucleoside analogues fails to show sufficient antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further study is warranted to evaluate the efficacy of a more potent tenofovir-based regimen in such patients.

Does 18F-FDG positron emission tomography-computed tomography have a role in initial staging of hepatocellular carcinoma?

Background and Aim The utility of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) in initial staging of hepatocellular carcinoma (HCC) has yet to be fully explored. We assessed the usefulness of 18F-FDG PET/CT in initial staging of HCC. Methods A total of 457 consecutive patients initially diagnosed with HCC at Seoul National University Hospital between 2006 and 2012 were evaluated retrospectively to assess the impact of 18F-FDG PET/CT on staging and compliancy with Milan criteria, relative to dynamic CT of liver and chest x-ray. Results Seven among the 457 patients studied showed a shift in Barcelona Clinic Liver Cancer [BCLC] stage (A→C: 6 patients; B→C: 1 patient) and 5 patients who had originally met Milan criteria no longer qualified. 18F-FDG PET/CT had value in initial staging of early (stage A) or intermediate (stage B) HCC, as determined by dynamic CT of liver and BCLC or AJCC classifications, whereas BCLC stage 0 and stage C tumors were unchanged (P<0.001). 18F-FDG PET/CT disclosed additional metastases in patients with American Joint Committee on Cancer [AJCC] T2 (2.7%), T3a (5.3%), and T3b (4.8%) classifications. Conclusions In initial staging of HCC, 18F-FDG PET/CT provided additional information, impacting the patients with BCLC (stages A and B) and AJCC (T2 and T3) classifications. Its use might be thus appropriate for these patient subsets, especially if hepatic resection or liver transplantation is planned.

High-sensitivity C-reactive protein level is an independent predictor of poor prognosis in cirrhotic patients with spontaneous bacterial peritonitis.

Background/Aims: The production of high-sensitivity C-reactive protein (hs-CRP) may be affected by hepatic function, and the clinical importance of hs-CRP in patients with liver cirrhosis is still not clear. The aim of this study was to evaluate the clinical implications of hs-CRP in cirrhotic patients with spontaneous bacterial peritonitis (SBP). Methods: We retrospectively investigated 336 consecutive patients treated for SBP from 2007 to 2012. The relationship between serum hs-CRP and the result of the treatment was assessed. Results: A response to antibiotics was observed in 182 patients (54.2%), and 126 patients (37.5%) died of SBP. The initial hs-CRP (odds ratio=1.061, P=0.016), coexistent hepatocellular carcinoma, and Child-Pugh (CP) score were independent prognostic factors for high in-hospital mortality. Serum hs-CRP level was also an independent predictor of lower antibiotic response rate (odds ratio=0.916, P<0.001). However, hs-CRP was negatively correlated with the CP score (r=−0.199, P<0.001) and Model for End-Stage Liver Disease score (r=−0.182, P=0.001). Conclusions: This study found that serum hs-CRP level is related to a lower response rate to antibiotics, a higher mortality rate in patients with SBP. The hs-CRP level was negatively correlated with the CP and Model for End-Stage Liver Disease scores, which suggests that the prognostic function of hs-CRP was not a surrogate for hepatic dysfunction.