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1.  Reversible splenial lesion on the corpus callosum in nonfulminant hepatitis A presenting as encephalopathy 
Clinical and Molecular Hepatology  2014;20(4):398-401.
Reversible focal lesions on the splenium of the corpus callosum (SCC) have been reported in patients with mild encephalitis/encephalopathy caused by various infectious agents, such as influenza, mumps, adenovirus, Varicella zoster, Escherichia coli, Legionella pneumophila, and Staphylococcus aureus. We report a case of a reversible SCC lesion causing reversible encephalopathy in nonfulminant hepatitis A. A 30-year-old healthy male with dysarthria and fever was admitted to our hospital. After admission his mental status became confused, and so we performed electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain, which revealed an intensified signal on diffusion-weighted imaging (DWI) at the SCC. His mental status improved 5 days after admission, and the SCC lesion had completely disappeared 15 days after admission.
PMCID: PMC4278072  PMID: 25548747
Acute hepatitis A; Encephalopathy; Magnetic resonance imaging; Corpus callosum
2.  Short-term interval combined chemoembolization and radiofrequency ablation for hepatocellular carcinoma 
World Journal of Gastroenterology : WJG  2014;20(35):12588-12594.
AIM: To investigate hepatic function after combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) with a short-term interval (0-2 d).
METHODS: A total of 115 patients with compensated liver cirrhosis underwent RFA combined with TACE at a time-interval of 0-2 d for the treatment of hepatocellular carcinoma (HCC) < 5.0 cm. There were 21 patients who received further hepatic directed treatment altering liver function within 12 mo after the combined therapy for HCC-recurrence, and were excluded. The remaining 94 patients who survived without HCC-recurrence were included in this retrospective study.
RESULTS: At 1 mo after treatment, Child-Pugh scores (CPs) remained unchanged in 89 of 94 patients (94.7%), and transiently increased by one-point in 5 patients (5.3%). However, the score returned to baseline score at 3 mo and was maintained until 6 mo in all patients. The baseline CPs of 8 or more was identified as a factor for transient rise of CPs after the treatment (CPs 8/9 vs 5/6/7; 21.4% vs 2.5%; P = 0.022). At 12 mo follow-up, CPs was unchanged in 90 patients (95.7%), and increased by one-point in 4 patients (4.3%). The rise of CPs at 12 mo was not statistically associated with the initial transient rise of CPs. There were procedure-related complications in 3 patients (3.2%), but the complications were resolved by medical and interventional treatments without hepatic functional sequelae.
CONCLUSION: The combined TACE and RFA with an interval of 0-2 d are safe for the management of HCC < 5 cm in cirrhotic patients.
PMCID: PMC4168095  PMID: 25253962
Child-Pugh score; Liver cirrhosis; Hepatocellular carcinoma; Transcatheter arterial chemoembolization; Radiofrequency ablation
3.  Clonal evolution of hepatitis B virus polymerase gene mutations during lamivudine-adefovir combination treatment 
AIM: To identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudine-adefovir sequential monotherapy followed by lamivudine-adefovir combination therapy.
METHODS: The patient cohort included four adult chronic hepatitis B patients who had undergone sequential monotherapy, first with lamivudine (LMV) and then, after developing viral breakthrough, with adefovir (ADV) therapy. All of the patients had non-response or viral breakthrough after LMV-ADV sequential monotherapy, which resulted in the switching of their antiviral regimen to LMV-ADV combination therapy. Eleven serum samples from the four patients who showed non-response to rescue LMV-ADV combination therapy were collected sequentially at a time before the antiviral treatment and then during the LMV monotherapy, ADV monotherapy, and LMV-ADV combination therapy. For the genotypic analysis, the whole 1310-bp polymerase gene region was amplified, cloned and sequenced.
RESULTS: All patients had been previously treated with 100 mg of LMV once daily for a 15- to 26-mo period. The emergence of resistance mutations to LMV, such as rtM204V/I and/or rtL180M, were found in all patients. Their antiviral regimens were switched to ADV monotherapy as the second line treatment. All patients had viral breakthrough or non-response after the LMV-ADV sequential monotherapy. ADV-resistant mutations were detected after 13 to 19 mo of LMV-ADV sequential monotherapy. The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-resistant patients. Twenty-seven of 38 clones were combined with an amino acid change at rt181; three clones had mutations in rt236 and one clone had a combined mutation. The rtA181V/T mutations were not suppressed by the LMV-ADV combination therapy. Thirty-nine of 64 clones showed an rtA181V/T mutation and six clones showed combined mutations in rt181 and rt236. Mutations in rt204 re-emerged during the combination treatment. The rt181 and rt204 mutations did not co-exist in one clone.
CONCLUSION: Add-on lamivudine therapy with adefovir for adefovir resistance may not suppress the pre-existing adefovir-resistant mutation that develops during lamivudine-adefovir sequential monotherapy.
PMCID: PMC3508638  PMID: 23197889
Hepatitis B virus; Lamivudine; Adefovir; Mutation; Drug resistance
4.  Efficacy and Safety of Tenofovir-Based Rescue Therapy for Chronic Hepatitis B Patients with Previous Nucleo(s/t)ide Treatment Failure 
Gut and Liver  2013;8(1):64-69.
We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies.
Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored.
Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log10 IU/mL to 2.0 log10 IU/mL and to 1.6 log10 IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed.
TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients' adherence to medication is related to viral rebound.
PMCID: PMC3916689  PMID: 24516703
Antiviral agents; Treatment outcome; Hepatitis B; Resistance; Tenofovir
5.  The Impact of the Hepatitis B Virus Polymerase rtA181T Mutation on Replication and Drug Resistance Is Potentially Affected by Overlapping Changes in Surface Gene 
Journal of Virology  2014;88(12):6805-6818.
The emergence of drug-resistant hepatitis B virus (HBV) is a major problem for antiviral treatment in chronic hepatitis B infection. In this study, we analyzed the evolution of drug-resistant mutations and characterized the effects of the rtA181T and rtI233V mutations on viral replication and drug resistance. We performed a clonal analysis of the HBV polymerase gene from serum samples during viral breakthrough treated with antiviral agents. A series of mutant clones containing rtA181T and/or rtI233V mutations were constructed and determined the effect of these mutations on the replication ability and drug resistance. An in vitro study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. Compared to the rtA181T surface missense mutation (rtA181T/sW172S), the introduction of rtA181T surface nonsense mutation (rtA181T/sW172*) resulted in decreased viral replication and increased drug resistance. Complementation assay revealed that the truncated PreS1 is responsible for reduced replication of rtA181T/sW172* mutant. Moreover, the rtA181T/sW172* mutant exhibited a defect in viral particle secretion. The rtI233V mutation that emerged during adefovir therapy reduced viral replication and conferred resistance to adefovir. Our data suggest that the impact of the rtA181T mutation on replication and drug resistance differs based on the mutation status of the corresponding surface gene. The rtI233V mutation also affects replication ability and drug resistance. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation.
IMPORTANCE The emergence of drug-resistant HBV that are no longer susceptible to nucleos(t)ide analogues is a major problem for antiviral treatment in chronic hepatitis B infection. Among drug-resistant mutations, the single rtA181T mutation is known to confer cross-resistance to antiviral drugs. This mutation causes intermediate or reduced susceptibility to tenofovir. Moreover, the clinical occurrence of the rtA181T mutation during antiviral therapy is also high. Our study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation. We believe that our study will not only extend the understanding of the drug resistance mechanism, but it will also ultimately provide new treatment options for patients with multidrug resistant HBV.
PMCID: PMC4054353  PMID: 24696492
6.  Virological Response and Muscular Adverse Events during Long-Term Clevudine Therapy in Chronic Hepatitis B Patients 
Hepatitis Monthly  2013;13(4):e6056.
Recently, several reports issued clevudine induced myopathy in the long term use.
The aim of this study was to investigate antiviral effects and adverse events of clevudine monotherapy in patients with chronic hepatitis B (CHB).
Patients and Methods
The subjects were 110 treatment-naïve CHB patients. They were treated with 30 mg clevudine/day for more than six months. Virological and biochemical tests, including that for serum creatine kinase (CK), were monitored at baseline and at 3-month intervals during treatment period.
In HBeAg-positive patients, the cumulative rates of virological response were 74.0 %, 68.5 %, and 67.3 % after one, two, and three years of clevudine treatment, respectively. Cumulative rates of HBeAg loss or seroconversion were 17.8 %, 30 %, and 31.5 % after one, two and, three years of clevudine treatment, respectively. In HBeAg-negative patients, the cumulative rates of virological response were 97.3 %, 100 %, and 94.6 %, respectively. Virological breakthrough occurred in 27 patients. The rtM204I mutation in HBV polymerase was predominantly detected. Muscular adverse events were observed in 15 patients. All patients with myopathy recovered after the cessation of clevudine monotherapy. Fluctuations in CK level during the clevudine treatment period were frequently observed irrespective of development of myopathy. Multiple episodes of CK elevation were significantly related to the development of myopathy.
Long-term clevudine monotherapy is effective for suppression of serum HBV DNA level and normalization of serum alanine amino transaminase levels, but associated with occurrence of rtM204I mutation. Clevudine-induced muscular adverse events are not uncommon, although they are totally reversible after cessation of the treatment. Muscular adverse events and serum CK level should be carefully monitored during long-term treatment with clevudine.
PMCID: PMC3693539  PMID: 23805155
Hepatitis B, Chronic; 2'-fluoro-5-methylarabinosyluracil; Response Elements; Adverse Effect; Hepatitis B, Chronic; 2'-fluoro-5-methylarabinosyluracil; Response Elements; Adverse Effect
7.  Hepatitis B surface antigen levels at 6 months after treatment can predict the efficacy of lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B 
Clinical and Molecular Hepatology  2014;20(3):274-282.
Quantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy.
LMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment.
Fifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020).
The HBsAg level at 6 months after treatment can help predict treatment response.
PMCID: PMC4197176  PMID: 25320731
Hepatitis B, Chronic; Hepatitis B surface antigen; Lamivudine; Adefovir; Resistance
8.  A synchronous hepatocellular carcinoma and renal cell carcinoma treated with radio-frequency ablation 
Clinical and Molecular Hepatology  2014;20(3):306-309.
Radio-frequency ablation (RFA) is a curative treatment for hepatocellular carcinoma (HCC). Percutaneous RFA has been shown to be beneficial for patients with small renal cell carcinoma (RCC) lacking indications for resection. We experienced the case of a 53-year-old male who had conditions that suggested HCC, RCC, and alcoholic liver cirrhosis. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance image showed liver cirrhosis with 2.8 cm ill-defined mass in segment 2 of the liver and 1.9 cm hypervascular mass in the left kidney. These findings were compatible with the double primary cancers of HCC and RCC. Transarterial chemoembolization (TACE) was performed to treat the HCC. After the TACE, a focal lipiodol uptake defect was noticed on a follow up CT images and loco-regional treatment was recommended. Therefore, we performed RFAs to treat HCC and RCC. There was no evidence of recurrence in the follow up image after 1 month.
PMCID: PMC4197180  PMID: 25320735
Hepatocellular carcinoma; Renal cell carcinoma; Radiofrequency ablation
9.  Rapid re-emergence of YMDD mutation of hepatitis B virus with hepatic decompensation after lamivudine retreatment 
Lamivudine has a high rate of antiviral resistance. Sequential treatment of anti-hepatitis B virus (HBV) is commonly used for lamivudine resistance. We report 4 cases of patients with rapid redetection of HBV mutants during the lamivudine retreatment. The four patients received lamivudine as an initial treatment of HBV and adefovir and lamivudine as a rescue therapy consecutively. HBV-DNA level, YMDD mutations and adefovir -resistant mutations (RFMP) were tested every 3 mo during the sequential treatment. All the patients showed YMDD mutations during the initial lamivudine therapy. After adefovir therapy for lamivudine resistance, they showed viral breakthrough. Adefovir was switched to lamivudine, however, it did not induce viral suppression at all, rather increased HBV-DNA with rapid reemergence of the YMDD mutations. All the patients had ALT flares, and hepatic decompensation occurred in two patients. After switching to adefovir combined with entecavir or lamivudine for a rescue therapy, the patients had reduction in HBV-DNA and ALT improvement. These cases demonstrated that lamivudine retreatment of patients with preexposed lamivudine resistance leads to rapid reemergence of YMDD mutation with significant viral rebounds and subsequent hepatic decompensation. Sequential administration of lamivudine in patients with a prior history of YMDD mutation should be abandoned.
PMCID: PMC2731201  PMID: 18666338
Hepatitis B; Lamivudine; Adefovir dipivoxil; Mutations
10.  Alcoholic fatty liver disease elevates estimated coronary heart disease risk to levels comparable with those of nonalcoholic fatty liver disease in the Korean population: a cross-sectional study 
Clinical and Molecular Hepatology  2014;20(2):154-161.
A close relationship has been established between nonalcoholic fatty liver disease (NAFLD) and an elevated risk of coronary heart disease (CHD), but little is known about the association between alcoholic fatty liver disease (AFLD) and CHD risk. The aim of this study was to determine whether AFLD is associated with elevated CHD risk.
We retrospectively enrolled 10,710 subjects out of 11,469 individuals who visited the Konkuk University Health Care Center for a routine health checkup in 2010. AFLD was diagnosed made when the usual amount of alcohol consumption exceeded 210 g/week in males and 140 g/week in females for the previous 2 years and when hepatic steatosis was detected by liver ultrasonography. The 10-year risk for CHD was estimated using the Framingham Risk Score.
Hepatic steatosis was diagnosed in 4,142 of the 10,710 individuals (38.7%); the remainder (i.e., n=6,568) became the control group. The 4,142 individuals with hepatic steatosis were divided into two groups: NAFLD (n=2,953) and AFLD (n=1,189). The risk of CHD was higher in AFLD (6.72±0.12) than in the control group (5.50±0.04, P<0.001), and comparable to that in NAFLD (7.32±0.07, P=0.02).
Individuals with AFLD have an elevated 10-year risk of CHD that is comparable to those with NAFLD. Therefore, AFLD should be considered a significant risk for future CHD, and preventive measures should be considered earlier.
PMCID: PMC4099330  PMID: 25032181
Framingham risk score; Alcoholic fatty liver; Coronary heart disease risk
11.  Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal 
Clinical and Molecular Hepatology  2014;20(2):185-191.
A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.
The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.
Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.
Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.
PMCID: PMC4099334  PMID: 25032185
Hepatorenal syndrome; Cirrhosis; Acute kidney injury; Chronic kidney disease
12.  The refit model for end-stage liver disease-Na is not a better predictor of mortality than the refit model for end-stage liver disease in patients with cirrhosis and ascites 
The modification of the Model for End-Stage Liver Disease (MELD) scoring system (Refit MELD) and the modification of MELD-Na (Refit MELDNa), which optimized the MELD coefficients, were published in 2011. We aimed to validate the superiority of the Refit MELDNa over the Refit MELD for the prediction of 3-month mortality in Korean patients with cirrhosis and ascites.
We reviewed the medical records of patients admitted with hepatic cirrhosis and ascites to the Konkuk University Hospital between January 2006 and December 2011. The Refit MELD and Refit MELDNa were compared using the predictive value of the 3-month mortality, as assessed by the Child-Pugh score.
In total, 530 patients were enrolled, 87 of whom died within 3 months. Alcohol was the most common etiology of their cirrhosis (n=271, 51.1%), and the most common cause of death was variceal bleeding (n=20, 23%). The areas under the receiver operating curve (AUROCs) for the Child-Pugh, Refit MELD, and Refit MELDNa scores were 0.754, 0.791, and 0.764 respectively; the corresponding values when the analysis was performed only in patients with persistent ascites (n=115) were 0.725, 0.804, and 0.796, respectively. The significant difference found among the Child-Pugh, Refit MELD, and Refit MELDNa scores was between the Child-Pugh score and Refit MELD in patients with persistent ascites (P=0.039).
Refit MELD and Refit MELDNa exhibited good predictability for 3-month mortality in patients with cirrhosis and ascites. However, Refit MELDNa was not found to be a better predictor than Refit MELD, despite the known relationship between hyponatremia and mortality in cirrhotic patients with ascites.
PMCID: PMC3992329  PMID: 24757658
Stage Liver Disease; Liver Cirrhosis; Ascites; Mortality; Hyponatremia
13.  Clinical Characteristics and Outcomes of Acute Hepatitis A in Korea: A Nationwide Multicenter Study 
Journal of Korean Medical Science  2014;29(2):248-253.
The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.
Graphical Abstract
PMCID: PMC3924005  PMID: 24550653
Hepatitis A; Morbidity; Mortality
14.  Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats 
Neuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain.
The neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction.
In comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor α (TNFα), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNFα and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group.
In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.
PMCID: PMC3927002  PMID: 24567814
Ketamine; Neuropathic pain; p38 MAPK; Proinflammatory cytokines
15.  HBsAg level and clinical course in patients with chronic hepatitis B treated with nucleoside analogue: five years of follow-up data 
Clinical and molecular hepatology  2013;19(4):409-416.
Quantification of the hepatitis B surface antigen (HBsAg) is increasingly used to determine the treatment response in patients with chronic hepatitis B (CHB). However, there are limited data about the clinical implications of Quantification of HBsAg long-term nucleoside analogue treatment for CHB. We investigated the clinical correlation between HBsAg level and clinical course in patients with CHB who are treated long-term with nucleoside analogues.
Patients with CHB who started lamivudine or entecavir monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at 6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between the groups according to the presence or absence of a virological response (VR) and resistance.
Forty-eight patients were analyzed. There was no definite reduction in HBsAg level during the early period of treatment; differences in HBsAg levels between baseline and each time point were significant only at 5 years (P=0.028). In a subgroup analysis, this difference was significant only in non-resistant patients at 5 years (P=0.041).
There was no definite decrease in the HBsAg level during the early period of nucleoside analogue treatment, with long-term treatment being required to observe a significant reduction.
PMCID: PMC3894441  PMID: 24459646
HBsAg; Chronic hepatitis B; Lamivudine; Entecavir; Resistance
16.  Sympathetically mediated upper back pain after coronary artery bypass graft surgery 
Korean Journal of Anesthesiology  2013;65(6 Suppl):S135-S136.
PMCID: PMC3903834  PMID: 24478846
17.  Lamivudine plus adefovir combination therapy for lamivudine resistance in hepatitis-B-related hepatocellular carcinoma patients 
Clinical and molecular hepatology  2013;19(3):273-279.
Lamivudine (LAM) plus adefovir (ADV) combination therapy has been accepted as one of the best treatments for LAM-resistant chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of this combination therapy in hepatocellular carcinoma (HCC) patients.
The medical records of CHB patients who developed LAM resistance and were treated with LAM plus ADV combination therapy for more than 6 months were reviewed. Their virological response (VR; undetectable HBV DNA) and biochemical response (BR; alanine aminotransferase normalization) were evaluated, and the findings of HCC and non-HCC patients were compared.
The data from 104 patients (19 with HCC and 85 without HCC) were analyzed. The VR rates did not differ significantly between the HCC and non-HCC groups: 33.3% vs. 55.6% at 12 months (P=0.119), 58.3% vs. 67.2% at 24 months (P=0.742), 50% vs. 69.8% at 36 months (P=0.280), and 66.7% vs. 71.0% at 48 months (P=1.000). The BR rates also did not differ significantly between the groups: 55.6% vs. 84.0% at 12 months (P=0.021), 58.3% vs. 83.8% at 24 months (P=0.057), 70.0% vs. 77.8% at 36 months (P=0.687), and 66.7% vs. 80.6% at 48 months (P=0.591).
The efficacy of LAM plus ADV combination therapy is comparable in HCC and non-HCC patients.
PMCID: PMC3796677  PMID: 24133665
Chronic hepatitis B; Lamivudine; Adefovir; Resistance; Hepatocellular carcinoma
18.  Laboratory characteristics of recent hepatitis A in Korea: Ongoing epidemiological shift 
AIM: To evaluate seroprevalence of hepatitis A virus (HAV) antibody and investigate demographic, clinical, and laboratory features of recent cases in Korea.
METHODS: For the evaluation of hepatitis A seroprevalence, we analyzed the data from 3127 subjects including, healthcare workers and patients who visited Konkuk University Hospital, a secondary referral center, from January to October 2009. The sera with positive IgM were excluded from seroprevalence data for total HAV antibody. We retrospectively reviewed the electronic medical records of 419 patients with HAV, who were diagnosed by the presence of serum IgM antibodies against HAV. All patients presented at Konkuk University Hospital between August 2005 and September 2008.
RESULTS: Among 3127 sera tested, 1428 (45.7%) were positive for anti-HAV antibody. The seroprevalence was very low in teenagers or those in their twenties, increased in those in their thirties, and was > 90% in older patients. In children younger than 10 years, seroprevalence was increased again. Most patients with HAV hepatitis were in their twenties and thirties. The γ-glutamyl transpeptidase increased with age and was significantly higher in patients older than 30 years. Indicators of severity, such as decreased albumin and increased bilirubin, were also more prominent in the older age group; however, the leukocyte count was higher and the frequency of leukopenia was lower in younger patients than in older adults.
CONCLUSION: There has been an apparent epidemiological shift in HAV seroprevalence and a change in the peak age of HAV hepatitis. This study could provide baseline data of recent hepatitis A in Asia.
PMCID: PMC2835789  PMID: 20205283
Hepatitis A virus; Seroprevalence; Epidemiology; Korea
19.  Importance of the surrounding colonic mucosa in distinguishing between hyperplastic and adenomatous polyps during acetic acid chromoendoscopy 
AIM: To examine the characteristics of colonic polyps, where it is difficult to distinguish adenomatous polyps from hyperplastic polyps, with the aid of acetic acid chromoendoscopy.
METHODS: Acetic acid spray was applied to colonic polyps smaller than 10 mm before complete excision. Endoscopic images were taken before and 15-30 s after the acetic acid spray. Both pre- and post-sprayed images were shown to 16 examiners, who were asked to interpret the lesions as either hyperplastic or adenomatous polyps. Regression analysis was performed to determine which factors were most likely related to diagnostic accuracy.
RESULTS: In 50 cases tested by the 16 examiners, the overall accuracy was 62.4% (499/800). Regression analysis demonstrated that surrounding colonic mucosa was the only factor that was significantly related to accuracy in discriminating adenomatous from hyperplastic polyps (P < 0.001). Accuracy was higher for polyps with linear surrounding colonic mucosa than for those with nodular surrounding colonic mucosa (P < 0.001), but was not related to the shape, location, or size of the polyp.
CONCLUSION: The accuracy of predicting histology is significantly related to the pattern of colonic mucosa surrounding the polyp. Making a histological diagnosis of colon polyps merely by acetic acid spray is helpful for colon polyps with linear, regularly patterned surrounding colonic mucosa, and less so for those with nodular, irregularly patterned surrounding colonic mucosa.
PMCID: PMC2700415  PMID: 18350630
Colon polyp; Chromoendoscopy; Acetic acid
20.  Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data 
While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.
The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.
The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).
The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.
PMCID: PMC3622854  PMID: 23593608
Gastric variceal bleeding; Rebleeding; Mortality; Cirrhosis
21.  Clinical outcomes of balloon-occluded retrograde transvenous obliteration for the treatment of gastric variceal hemorrhage in Korean patients with liver cirrhosis: a retrospective multicenter study 
Clinical and molecular hepatology  2012;18(4):368-374.
This study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC).
We retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010.
Of the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047).
BRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO.
PMCID: PMC3540373  PMID: 23323252
Balloon-occluded retrograde transvenous obliteration; Esophageal varices; Gastric varices; Liver cirrhosis; Variceal hemorrhage
22.  Is close monitoring in the intensive care unit necessary after elective liver resection? 
Many surgical patients are admitted to the intensive care unit (ICU), resulting in an increased demand, and possible waste, of resources. Patients who undergo liver resection are also transferred postoperatively to the ICU. However, this may not be necessary in all cases. This study was designed to assess the necessity of ICU admission.
The medical records of 313 patients who underwent liver resections, as performed by a single surgeon from March 2000 to December 2010 were retrospectively reviewed.
Among 313 patients, 168 patients (53.7%) were treated in the ICU. 148 patients (88.1%) received only observation during the ICU care. The ICU re-admission and intensive medical treatment significantly correlated with major liver resection (odds ratio [OR], 6.481; P = 0.011), and intraoperative transfusions (OR, 7.108; P = 0.016). Patients who underwent major liver resection and intraoperative transfusion were significantly associated with need for mechanical ventilator care, longer postoperative stays in the ICU and the hospital, and hospital mortality.
Most patients admitted to the ICU after major liver resection just received close monitoring. Even though patients underwent major liver resection, patients without receipt of intraoperative transfusion could be sent to the general ward. Duration of ICU/hospital stay, ventilator care and mortality significantly correlated with major liver resection and intraoperative transfusion. Major liver resection and receipt of intraoperative transfusions should be considered indicators for ICU admission.
PMCID: PMC3433552  PMID: 22977762
Hepatectomy; Major resection; Intensive care units; Intraoperative transfusion
23.  Increased expression of vascular endothelial growth factor in neo-vascularized canine brain tissue 
This retrospective study was done to characterize the levels of vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 (HIF-1α) in dog brains with neo-vascularization in the cerebral cortex of frontal, temporal, and parietal lobe by using immunohistochemistry (IHC) and Western blot. In neo-vascularized (NV) brains, we analyzed the number and area of blood vessels and the expression of VEGF and HIF-1α. The IHC results showed that the number and area of blood vessels, as assessed by immunolabeling for von Willebrand factor, was higher in the NV brain than in the control brain. The Western blot results showed that the level of VEGF was increased, predominantly in NV brain of the cerebral cortex relative to the clinically normal cerebral cortex, whereas the expression of HIF-1α in NV brains was not different from the control brains. Our study showed that dilatation of vessels and development of new vessels in the cerebral cortex were observed in cases of canine CNS disease and found increased expression of VEGF in canine brains with neo-vascularization.
PMCID: PMC3244290  PMID: 22754097
24.  Clinical features of acute viral hepatitis B in Korea: a multi-center study 
The Korean Journal of Hepatology  2011;17(4):307-312.
The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea.
A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009.
One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total-bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents.
The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment.
PMCID: PMC3304668  PMID: 22310795
Acute hepatitis B; Prevalence; Prognosis
25.  RPS3a Over-Expressed in HBV-Associated Hepatocellular Carcinoma Enhances the HBx-Induced NF-κB Signaling via Its Novel Chaperoning Function 
PLoS ONE  2011;6(8):e22258.
Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC) development. Hepatitis B virus X protein (HBx) is known to play a key role in the development of hepatocellular carcinoma (HCC). Several cellular proteins have been reported to be over-expressed in HBV-associated HCC tissues, but their role in the HBV-mediated oncogenesis remains largely unknown. Here, we explored the effect of the over-expressed cellular protein, a ribosomal protein S3a (RPS3a), on the HBx-induced NF-κB signaling as a critical step for HCC development. The enhancement of HBx-induced NF-κB signaling by RPS3a was investigated by its ability to translocate NF-κB (p65) into the nucleus and the knock-down analysis of RPS3a. Notably, further study revealed that the enhancement of NF-κB by RPS3a is mediated by its novel chaperoning activity toward physiological HBx. The over-expression of RPS3a significantly increased the solubility of highly aggregation-prone HBx. This chaperoning function of RPS3a for HBx is closely correlated with the enhanced NF-κB activity by RPS3a. In addition, the mutational study of RPS3a showed that its N-terminal domain (1–50 amino acids) is important for the chaperoning function and interaction with HBx. The results suggest that RPS3a, via extra-ribosomal chaperoning function for HBx, contributes to virally induced oncogenesis by enhancing HBx-induced NF-κB signaling pathway.
PMCID: PMC3156704  PMID: 21857917

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