Young Youn Cho

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.

Radioembolization Is a Safe and Effective Treatment for Hepatocellular Carcinoma with Portal Vein Thrombosis: A Propensity Score Analysis.

Background/Aims Limited treatment options are available for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Transarterial radioembolization using Yttrium-90 microspheres is a new treatment modality for HCC with PVT. For this analysis, we compared responses to treatment with radioembolization and with sorafenib. Methods We evaluated 32 patients who were part of a multicenter retrospective cohort. All patients had PVT without extrahepatic metastasis and were treated with radioembolization in one of six tertiary referral hospitals in Korea. We retrospectively enrolled another 31 consecutive PVT patients without extrahepatic metastasis from a single center who received sorafenib treatment to serve as the control group. We used inverse probability weighting (IPW) using propensity scores to adjust for the between-group differences in baseline characteristics. Results At 3 months, the response rate and disease control rate were 32.1% (9/32) and 57.1% (16/32), respectively, in the radioembolization group and 3.2% (1/31) and 41.9% (13/31) in the sorafenib group. Median overall survival (OS) and time to progression (TTP) were not significantly different between the radioembolization group and the sorafenib group (13.8 months and 10.0 months, P = 0.22; and 6.0 months and 6.0 months, P = 0.08; respectively). No differences in OS (P = 0.97) or TTP (P = 0.34) were observed after IPW was applied to balance the population characteristics. The sorafenib group showed significantly more grade 3/4 adverse effects than the radioembolization group (P < 0.01). Conclusion HCC patients with PVT who underwent radioembolization achieved comparable survival to patients who received sorafenib, even after application of IPW. The radioembolization group also experienced fewer severe adverse effects. Radioembolization can be considered a new treatment option for patients with HCC with PVT.

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.

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.

Efficacy of antiviral prophylaxis in HBsAg-negative, anti-HBc positive patients undergoing hematopoietic stem cell transplantation.

Hepatitis B virus (HBV) reactivation can occur in persons who are hepatitis B surface antigen (HBsAg)‐negative but hepatitis B core antibody (anti‐HBc) positive, especially following hematopoietic stem cell transplantation (HSCT). However, evidence supporting the routine use of prophylactic antiviral agents for such patients is scarce. The aim of this study was to compare the frequency of HBV reactivation between prophylactic and non‐prophylactic groups in patients who underwent HSCT.

Comparison of physical and mental health status between cancer survivors and the general population: a Korean population-based survey (KNHANES II-IV)

PurposeTo compare the physical and mental health status of the general population with that of cancer survivors in South Korea.MethodsWe analyzed 19,035 subjects (age ≥40xa0years), who participated in the 2001–2009 Korea National Health and Nutrition Examination Survey II–IV. We compared metabolic syndrome components, health behaviors, and mental health outcomes between cancer survivors and non-cancer controls.ResultsCancer survivors accounted for 1.68xa0% (nu2009=u2009316) of total population. Cancer survivors did not show low occurrence of hypertension and diabetes compared to the control group. Both cancer survivors and the general population had high risks of physical inactivity (75.4xa0% and 75.5xa0%, respectively) and inadequate sleep (52.5xa0% and 60.7xa0%, respectively). In the unadjusted model, depression was more common in cancer survivors (odds ratio [OR], 1.61; 95xa0% CI, 1.22–2.74), so was suicidal ideation (OR, 1.51; 95xa0% CI, 0.16–1.96) than non-cancer controls. After adjustment for attributable socioeconomic factors, the elevated adjusted odds ratios (aORs) among cancer survivors were reduced by 23xa0% in depression and 45xa0% in suicidal thought. Cancer survivors at <5xa0years from diagnosis showed a high occurrence of depression (aOR, 1.77; 95xa0% CI, 1.09–2.85) while the magnitude of aOR decreases after ≥5xa0years from cancer diagnosis (aOR, 1.38; 95xa0% confidence interval, 0.97–1.98, respectively).ConclusionsThe physical and mental health of South Korean cancer survivors was not optimal. Their control rates of modifiable risk factors were similar or even lower than those for the non-cancer groups. Depression was highly prevalent in cancer survivors which can be ascribed, at least in part, to socioeconomic environment. A better-targeted intervention to improve the health of this population may be needed.

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.

Antiplatelet therapy and the risk of hepatocellular carcinoma in chronic hepatitis B patients on antiviral treatment

Antiplatelet therapy has shown protective effects against hepatocellular carcinoma (HCC) in preclinical studies. However, it is unclear whether antiplatelet therapy lowers the risk of HCC in patients with chronic hepatitis B. A retrospective analysis was conducted of data from 1,674 chronic hepatitis B patients, enrolled between January 2002 and May 2015, whose serum hepatitis B virus DNA levels were suppressed by antivirals to <2,000 IU/mL. The primary and secondary outcomes were development of HCC and bleeding events, respectively. Risk was compared between patients with antiplatelet treatment (aspirin, clopidogrel, or both; antiplatelet group) and patients who were not treated (non‐antiplatelet group) using a time‐varying Cox proportional hazards model for total population and propensity score–matching analysis. The antiplatelet group included 558 patients, and the non‐antiplatelet group had 1,116 patients. During the study period, 63 patients (3.8%) developed HCC. In time‐varying Cox proportional analyses, the antiplatelet group showed a significantly lower risk of HCC (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23–0.85; Pu2009=u20090.01), regardless of antiplatelet agent. In propensity score–matched pairs, antiplatelet therapy significantly reduced the risk of HCC (HR, 0.34; 95% CI, 0.15‐0.77; Pu2009=u20090.01). However, the overall risk of bleeding was higher in the antiplatelet group (HR, 3.28; 95% CI, 1.98‐5.42; Pu2009<u20090.001), particularly for clopidogrel with or without aspirin. Treatment with aspirin alone was not associated with a higher bleeding risk (HR, 1.11; 95% CI, 0.48‐2.54; Pu2009=u20090.81). Conclusion: Antiplatelet therapy reduces the risk of HCC in chronic hepatitis B patients whose hepatitis B virus is effectively suppressed. However, antiplatelet therapy containing clopidogrel may increase the risk of bleeding. (Hepatology 2017;66:1556–1569)