Beom Kyung Kim

Yonsei University Hospital, Sŏul, Seoul, South Korea

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Publications (59)197.49 Total impact

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    ABSTRACT: Background&AimsLiver stiffness (LS) measurement using transient elastography and the FibroTest (FT) are alternatives to liver biopsy (LB) in assessing liver fibrosis. We investigated the prognostic role of the combined use of LS and FT in predicting liver-related events (LREs) in patients with chronic hepatitis B (CHB).Methods Consecutive patients with CHB who underwent LB, along with LS and FT on the same day from 2007 to 2010 were recruited. LRE was defined as hepatic decompensation, hepatocellular carcinoma (HCC), or liver-related death.ResultsA total of 151 patients (86 male) were analyzed. During follow-up (median 59.9 months), overall 18 (11.9%) patients experienced LREs. The areas under receiver-operating characteristic curves of LS, FT, LS+FT and LSxFT in predicting LRE were 0.701, 0.668, 0.702 and 0.741, respectively. After adjusting for age and histological fibrosis staging, significant variables in univariate analysis (both P<0.05), LS+FT and LSxFT were independent predictors of LREs with hazard ratios (HRs) of 1.080 and 1.126 (all P<0.05), respectively. When subjects were divided into three groups according to quartile stratification (low quartile, interquartile and high quartile) using LS+FT and LSxFT, cumulative LRE development rate significantly increased with a corresponding increase in value among three groups, respectively (log-rank test, all P<0.05).Conclusion The combined use of LS and FT significantly predicted forthcoming LRE development, but with only a slight additional benefit compared to LS or FT alone.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 09/2014; · 3.87 Impact Factor
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    ABSTRACT: The controlled attenuation parameter (CAP) is a noninvasive method of assessing hepatic steatosis. We defined the normal range of CAP values in healthy subjects and evaluated the associated factors.
    Digestive Diseases and Sciences 08/2014; · 2.26 Impact Factor
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    ABSTRACT: Backgrounds/Aims:Serum fibrosis markers such as Enhanced Liver Fibrosis (ELF) test, have been suggested as alternatives for liver biopsy (LB) in assessing liver fibrosis. We investigated the efficacy of ELF test in predicting development of liver-related events (LRE) in patients with chronic hepatitis B (CHB).Methods:A total of 170 patients (103 men, 60.6%) with CHB who underwent LB and serological tests for determining ELF were enrolled. All patients were followed-up to monitor LRE development, defined as hepatic decompensation, hepatocellular carcinoma, and/or liver-related death.Results:The mean age was 45.3 years. During follow-up period (median, 41 months), 39 (22.9%) patients experienced LRE. In patients with LRE, age, proportion of male gender, ELF test results, age–spleen–platelet ratio (ASPRI), liver stiffness (LS) value, and histological fibrosis stage were significantly higher than those in patients without LRE (all P<0.05). Areas under receiver-operating characteristic curves to predict LRE development were 0.808 for ELF test, 0.732 for LS value, 0.713 for histological fibrosis stages using Batts and Ludwig scoring system, and 0.687 for ASPRI. On multivariate analysis, along with age, ELF test was an independent predictor of LRE development (adjusted hazard ratio [HR] 1.438, P<0.001). When we applied a three-tier stratification of our study population using cut-off ELF values of 8.10 and 10.40, patients with low (P=0.002; adjusted HR 0.045, 95% confidence interval [CI] 0.006–0.330) and intermediate (P<0.001; adjusted HR 0.239, 95% CI 0.122–0.469) ELF range were found less likely to develop LRE compared to those with high ELF range.Conclusion:ELF is useful in a non-invasive prediction of LRE development. TE showed statistically similar prognostic performance for LRE as ELF, but other non-invasive tests were inferior. (Hepatology 2014;)
    Hepatology 08/2014; · 12.00 Impact Factor
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    ABSTRACT: Advanced cancer patients with refractory ascites often do not respond to conventional treatments including dietary sodium restriction, diuretics, and repeated large volume paracentesis. In these patients, continuous peritoneal drainage by an indwelling catheter may be an effective option for managing refractory ascites with a relative low complication rate. Peritoneal catheter-induced complications include hypotension, hematoma, leakage, cellulitis, peritonitis, and bowel perforation. Although bowel perforation is a very rare complication, it can become disastrous and necessitates emergency surgical treatment. Herein, we report a case of a 57-year-old male with refractory ascites due to advanced liver cancer who experienced iatrogenic colonic perforation after peritoneal drainage catheter insertion and was treated successfully with endoscopic clipping. (Korean J Gastroenterol 2014;63:373-377).
    06/2014; 63(6):373-7.
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    ABSTRACT: OBJECTIVES:In the era of antiviral therapy, the prognostic significance of serum hepatitis B virus (HBV) DNA level as a biological gradient substantially diminished, as most patients can achieve complete virological response (CVR). We aimed to investigate the predictive roles of liver stiffness (LS) for liver-related events (LREs) among patients with CVR.METHODS:We analyzed 192 patients with chronic HBV infection who achieved CVR (defined as HBV DNA <20 IU/ml) through entecavir therapy. LS values at CVR were measured using transient elastography. LREs were defined as any cirrhotic complication, hepatocellular carcinoma, and liver-related mortality.RESULTS:The median age of the patients was 49 years, and 134 (69.8%) were male. The median LS value at CVR was 8.8 kPa. During follow-up, LREs occurred in 25 (13.0%) patients. When the population was stratified into three groups (<8.0 kPa, 8.0-13.0 kPa, and >13.0 kPa), cumulative LRE incidences increased significantly in association with LS values (log-rank test, P=0.001). Patients with an LS value >13.0 kPa (hazard ratio (HR)=12.336, 95% confidence interval (CI) 1.335-114.010; P=0.027) and 8.0-13.0 kPa (HR=8.832, 95% CI 1.092-71.432; P=0.041) were at significantly greater risk compared with those with an LS value <8.0 kPa. On multivariate analysis, age and LS values were seen to be independent predictors (all P<0.05). When LS values were incorporated into the REACH-B scoring model instead of serum HBV DNA level, a better predictive performance was seen compared with a conventional approach (areas under the receiver operating characteristic curve, 0.814 vs. 0.629, respectively).CONCLUSIONS:LS values at CVR are useful for predicting forthcoming LRE development. Thus, in the era of potent antiviral therapy, tailored surveillance strategies might be established based upon LS values at CVR.Am J Gastroenterol advance online publication, 24 June 2014; doi:10.1038/ajg.2014.157.
    The American journal of gastroenterology. 06/2014;
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    ABSTRACT: Liver stiffness (LS) value using transient elastography is a reliable, noninvasive tool for assessing liver fibrosis. LS-based prediction model, LSPS (= LS value x spleen diameter/platelet count) is well correlated with the risk of developing portal hypertension-related cirrhotic complications. Here, we assessed the prognostic performance of LSPS in predicting the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).
    Liver international: official journal of the International Association for the Study of the Liver 06/2014; · 3.87 Impact Factor
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    ABSTRACT: This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection.
    Annals of Surgical Oncology 06/2014; · 4.12 Impact Factor
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    ABSTRACT: Backgrounds and AimsIn chronic hepatitis B virus (HBV) infection, quantitative HBV surface antigen (qHBsAg) is useful for monitoring viral replication and treatment responses. We aimed to determine whether pre-S mutations have any effect on circulating qHBsAg.Methods Plasmids expressing 1–8 amino acid deletion in pre-S1 (“pre-S1Δ1-8”) and 3-25 amino acid deletion in pre-S2 (“pre-S2Δ3-25”) were constructed. At 72 h post-transfection into Huh7 cells, qHBsAg were measured using electrochemiluminescence immunoassay analyzer. To mimic milieus of quasispecies, we co-transfected either pre-S1Δ1-8 or pre-S2Δ3-25 with wild type (WT).ResultsPre-S mutations affected transcription and replication ability of HBV because of altered overlapping polymerase. Compared with WT, extracellular qHBsAg in pre-S1Δ1-8 and pre-S2Δ3-25 were on average 3.87-fold higher and 0.92-fold lower, respectively, whereas intracellular qHBsAg in pre-S1Δ1-8 and pre-S2Δ3-25 were 0.57-fold lower and 1.60-fold higher, respectively. Immunofluorescence staining of cellular HBsAg showed that pre-S1Δ1-8 had less staining and that pre-S2Δ3-25 had denser staining. As ratios of either pre-S1Δ1-8 or pre-S2Δ3-25:WT increased from 0:10 to 10:0 gradually, relative extracellular qHBsAg increased from 1.0 to 3.85 in pre-S1Δ1-8 co-transfection, whereas those decreased from 1.0 to 0.88 in pre-S2Δ3-25 co-transfection.Conclusion Pre-S mutations exhibit different phenotypes of genome replication and HBsAg expression according to their locations. Thus, qHBsAg level for diagnosis and prognostification in chronic HBV infection should be used more cautiously, considering emergences of pre-S deletion mutants.
    Journal of Gastroenterology and Hepatology 04/2014; 29(4). · 3.33 Impact Factor
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    ABSTRACT: Although advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is recommended to be treated by a systemic chemotherapeutic agent without local treatment targeting the liver, studies reported that causes of death in these patients were mostly from progression of intrahepatic lesions. Thus, this study investigated prognosis and factors predicting survival in these patients so as to evaluate the role of local treatments against intrahepatic lesions when the patients already had extrahepatic metastasis. This retrospective study evaluated medical records of 277 patients with HCC and extrahepatic metastasis. The median survival was 5.9 months, and 257 patients died during the follow up. Factors affecting survival of HCC patients with extrahepatic metastasis were poor response to treatment of hepatic lesions (HR 2.207; 95 % CI; p < 0.001), applying local treatment specifically targeting intrahepatic lesions (HR 0.591; 95 % CI 0.436-0.803; p = 0.001), intrahepatic tumor size larger than 3 cm (HR 2.065; 95 % CI 1.444-2.954; p < 0.001), and ECOG performance status 2 or higher (HR 1.543; 95 % CI 1.057-2.253; p = 0.025). The patients with either complete or partial response to the therapy had 1- and 2-year survival rate of 48.8 and 12.1 % whereas patient with either stable or progressive disease had 1-year survival rate of 11.4 %. These results suggest that even in the HCC patients with extrahepatic metastasis, effective local treatment may still be beneficial for the survival especially in patients with acceptable performance status.
    Clinical and Experimental Metastasis 02/2014; · 3.46 Impact Factor
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    ABSTRACT: Background/AimsSorafenib is recommended as a standard treatment for advanced hepatocellular carcinoma (HCC). We investigated the efficacy and safety of sorafenib as a first-line therapy in Korean patients with advanced HCC. Methods From 2007 to 2012, 86 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) treated with sorafenib as a first-line therapy were enrolled from five tertiary hospitals. Predictors of overall survival (OS) and progression-free survival (PFS) were analyzed. ResultsThe median age was 59.5 years and 71 (82.6%) were males; 57 (66.3%) patients were in Child-Pugh class A. The median OS and PFS were 5.0 (range, 4.0-5.9) and 3.2 (range, 2.6-3.7) months, respectively. Regarding OS, Child-Pugh class A (6.0 vs. 2.8 months), tumor diameter < 5 cm (6.0 vs. 4.3 months), baseline α-fetoprotein (AFP) < 200 ng/mL (5.8 vs. 4.1 months), and the advent of hand-foot-skin reaction (HFSR) of ≥ grade 2 (5.9 vs. 4.0 months) were independent favorable predictors (all P < 0.05). Similarly, regarding PFS, Child-Pugh class A (4.3 vs. 2.1 months), tumor diameter < 5 cm (3.9 vs. 2.8 months), baseline AFP < 200 ng/mL (5.6 vs. 2.8 months) and the advent of HFSR of ≥ grade 2 (4.5 vs. 2.6 months) were independent favorable predictors (all P < 0.05). All toxicities during sorafenib treatment were manageable. Conclusions Because the efficacy of sorafenib seems marginal in Korean patients with treatment-naïve HCC, how to select candidates with favorable outcomes should be further investigated.
    Journal of Gastroenterology and Hepatology 02/2014; · 3.33 Impact Factor
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    ABSTRACT: Spontaneous bacterial peritonitis (SBP) is a common and life-threatening infection in patients with advanced cirrhosis. The prognostic value of a novel marker, the delta neutrophil index (DNI), was investigated relative to mortality in patients with SBP. Seventy-five patients with SBP were studied from April 2010 to May 2012. DNI at initial diagnosis of SBP was determined and compared with 30-day mortality rates. Of the patients, 87.7% were men, and the median age of all patients was 59.0 yrs. The area under the receiver-operating characteristic (ROC) curve of DNI for 30-day mortality was 0.701 (95% confidence interval [CI], 0.553-0.849; p = 0.009), which was higher than that of C-reactive protein (0.640, 95% CI, 0.494-0.786; p = 0.076) or the model for end-stage liver disease score (0.592, 95% CI, 0.436-0.748; p = 0.235). From the ROC curve, with the sum of sensitivity and specificity, the cutoff value of DNI was determined to be 5.7%. In the high-DNI group (DNI ≥5.7%), septic shock and 30-day mortality were more prevalent compared with the low-DNI group (84.2% vs. 48.2%, p = 0.007; 57.9% vs. 14.3%, p<0.001, respectively). Patients with an elevated DNI had a higher risk of 30-day mortality compared with those with a low DNI (4.225, 95% CI, 1.631-10.949; p = 0.003). A higher DNI at the time of SBP diagnosis is an independent predictor of 30-day mortality in patients with SBP.
    PLoS ONE 01/2014; 9(1):e86884. · 3.53 Impact Factor
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    ABSTRACT: Controlled attenuation parameter (CAP) can measure hepatic steatosis. However, factors affecting its accuracy have not been described yet. This study investigated predictors of discordance between liver biopsy (LB) and CAP.
    PLoS ONE 01/2014; 9(6):e98689. · 3.53 Impact Factor
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    ABSTRACT: Preoperative liver stiffness (LS) measurement using transient elastography (TE) is useful for predicting late recurrence after curative resection of hepatocellular carcinoma (HCC). We developed and validated a novel LS value-based predictive model for late recurrence of HCC.
    PLoS ONE 01/2014; 9(6):e99167. · 3.53 Impact Factor
  • Seung Up Kim, Beom Kyung Kim, Kwang-Hyub Han
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    ABSTRACT: Liver biopsy (LB) remains the gold standard for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra-/inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are ineligible in real clinical practice. Thus, due to the pressing need for non-invasive surrogates, over the past decade, significant progress has been made in non-invasively assessing liver fibrosis. Of the methods now available, transient elastography (TE) appears to be an excellent tool for assessing liver fibrosis and also has some prognostic value in surgical settings. Recent studies have proposed the extended role of TE in the surgical field, based on the concept that TE values show significant correlations with portal hypertension and hepatocellular carcinoma development. TE appears promising in predicting postoperative short-term outcomes such as hepatic insufficiency or complications and long-term outcomes such as recurrence or liver-related death. Furthermore, TE may be useful in predicting the severity of liver fibrosis progression due to recurrence of hepatitis C virus infection or other underlying liver diseases after transplantation. TE cannot completely replace other tests accompanied with hepatic surgical treatments, including LB, endoscopic examination, hepatic venous pressure gradient evaluation, or the indocyanine green retention test. However, TE represents an important non-invasive tool that enables more efficient and tailored management strategies for patients who were treated with liver resection or transplantation. This review discusses extended TE applications in the surgical setting, such as hepatic resection or transplantation. © 2013 S. Karger AG, Basel.
    Digestion 12/2013; 88(4):258-265. · 1.94 Impact Factor
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    ABSTRACT: Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC), and ultimately liver-related deaths. Recently, owing to potent antiviral therapy with minimal side effects, sustained suppression of hepatitis B virus replication can be achieved, thereby preventing such complications. We aimed to reappraise clinical courses regarding disease progression in the era of antiviral therapy. Between 2001 and 2005, treatment-naïve Korean CHB patients without cirrhosis were enrolled and follow-up for at least 5 years. During follow-up, antiviral therapy was commenced according to Korean Association for the Study of the Liver guidelines, if eligible, and ultrasonography and laboratory and clinical assessment were performed regularly. Primary endpoints were development of cirrhosis, hepatic decompensation, HCC, or liver-related deaths. Of 360 patients, 323 (89.7%) received antiviral therapy such as lamivudine (70.6%), entecavir (8.7%), or telbivudine (6.5%). During follow-up, cirrhosis developed in 29 (8.1%), hepatic decompensation in 4 (1.1%), and HCC in 15 (4.2%) patients. Annual incidences of cirrhosis, hepatic decompensation, and HCC were 1.05%, 0.14%, and 0.53% per person-year, respectively. Age was an independent predictor for developing cirrhosis (hazard ratio [HR] 1.075, 95% confidence interval [CI] 1.037-1.116; p<0.001), whereas age (HR 1.060, 95% CI 1.012-1.111; p=0.014) and cirrhosis (HR 17.470, 95% CI 5.081-60.063; p<0.001) were those for developing HCC. In the era of antiviral therapy, overall clinical courses have been much improved since introduction of lamivudine in 1999. However, patients with older age or cirrhosis are still subject to HCC development despite appropriate antiviral therapy, necessitating cautious surveillance.
    Journal of Gastroenterology and Hepatology 12/2013; · 3.33 Impact Factor
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    ABSTRACT: Liver stiffness (LS) measurement using transient elastography allows for accurate evaluation of liver fibrosis in patients with chronic liver disease. We aimed to investigate the influence of antiviral treatment using entecavir (ETV) on LS values in patients with chronic hepatitis B (CHB). 121 patients with CHB who completed a 3-year ETV treatment were recruited. LS values were measured before starting ETV (baseline) and after the completion of the 3-year treatment. A significant decline in the LS value was defined as a ≥30% drop from the baseline. The median baseline LS value of the patients was 14.3 kPa. However, it decreased significantly to 7.3 kPa after 3-year ETV treatment (P < 0.001). A higher baseline LS value was the single independent predictor of a significant decline in LS value on multivariate analysis (P<0.001; hazard ratio [HR], 1.155; 95% confidence interval [CI], 1.073-1.243). Using an optimal cutoff baseline LS value of 11.5 kPa (area under receiver operating characteristic curve, 0.781; 95% CI, 0.698-0.863, P < 0.001; sensitivity 75.6%; specificity, 62.8%), patients with baseline LS values of ≥11.5 kPa had a greater probability of experiencing a significant decline in the LS value than those with baseline LS values of <11.5 kPa (P < 0.001; HR, 5.240; 95% CI, 2.340-11.732). In patients with CHB, LS values were decreased significantly after a 3-year ETV treatment. A higher baseline LS value was the single independent predictor of a significant decline in the LS value.
    Liver international: official journal of the International Association for the Study of the Liver 11/2013; · 3.87 Impact Factor
  • European journal of gastroenterology & hepatology 04/2013; 25(4):514-5. · 1.66 Impact Factor
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    ABSTRACT: Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE), as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.
    World Journal of Gastroenterology 03/2013; 19(12):1890-900. · 2.55 Impact Factor
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    Mi Na Kim, Beom Kyung Kim, Kwang-Hyub Han
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality worldwide. Although hepatitis B still remains the most common risk factor worldwide, chronic hepatitis C virus (HCV) infection is the driving force for the increased incidence of HCC especially in Western countries and Japan. In hepatitis B virus (HBV)-endemic areas, after successful vaccination programs against HBV, chronic HCV infection is now emerging as an important cause of chronic liver diseases. Unlike patients with chronic hepatitis B, those with chronic hepatitis C (CHC) develop HCC in the presence of established cirrhosis in most cases. However, a significant minority of CHC develops HCC in the absence of cirrhosis. Although HCV is a RNA virus with little potential for integrating its genetic material into host genome, various HCV proteins, including core, envelope, and nonstructural proteins, have oncogenic properties by inducing oxidative stress, disturbing cellular regulatory pathways associated with proliferation and apoptosis, and suppressing host immune responses. Overall, a combination of virus-specific, host genetic, environmental, and immune-related factors are likely to determine progression to HCC. Strategies aimed at eliminating the virus may provide opportunities for effective prevention of the development of HCC. Pegylated interferon plus ribavirin therapy appears to be effective at reducing the risk of HCC in patients who achieve sustained virologic responses. In summary, with the emerging importance of CHC, mechanisms of HCV-associated hepatocellular carcinogenesis should be clarified to provide insight into advanced therapeutic and preventive approaches, which eventually decrease the incidence and mortality of HCC.
    Journal of Gastroenterology 03/2013; · 3.79 Impact Factor
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    ABSTRACT: The incidence of multidrug-resistant (MDR) chronic hepatitis B (CHB) during sequential lamivudine (LAM) and adefovir dipivoxil (ADV) treatment is increasing. We investigated the antiviral efficacies of various rescue regimens in patients who failed sequential LAM-ADV treatment. Forty-eight patients (83.3% of whom were HBeAg-positive) who failed sequential LAM-ADV treatment were treated with one of the following regimens: entecavir (ETV) (1 mg) monotherapy (n=16), LAM+ADV combination therapy (n=20), or ETV (1 mg)+ADV combination therapy (n=12). All patients had confirmed genotypic resistance to both LAM and ADV and were evaluated every 12 weeks. The baseline characteristics and treatment duration did not differ significantly among the study groups. During the treatment period (median duration: 100 weeks), the decline of serum HBV DNA from baseline tended to be greatest in the ETV+ADV group at all-time points (week 48: -2.55 log10 IU/mL, week 96: -4.27 log10 IU/mL), but the difference was not statistically significant. The ETV+ADV group also tended to have higher virologic response rates at 96 weeks compared to the ETV monotherapy or LAM+ADV groups (40.0% vs. 20.0% or 20.0%, P=0.656), and less virologic breakthrough was observed compared to the ETV monotherapy or LAM+ADV groups (8.3% vs. 37.5% or 30.0%; P=0.219), but again, the differences were not statistically significant. HBeAg loss occurred in one patient in the ETV+ADV group, in two in the ETV monotherapy group, and in none of the LAM+ADV group. The safety profiles were similar in each arm. There was a nonsignificant tendency toward better antiviral efficacy with ETV+ADV combination therapy compared to LAM+ADV combination therapy and ETV monotherapy for MDR CHB in Korea, where tenofovir is not yet available.
    Clinical and molecular hepatology. 03/2013; 19(1):29-35.