Seok Lee

Continuous Long-Term Entecavir Therapy in Naïve Chronic Hepatitis B Patients Showing Partial Virologic Response

Background/Aims We investigated the efficacy of continuous long-term entecavir 0.5 mg treatment in naïve chronic hepatitis B patients showing a partial virologic response (PVR). Methods A total of 227 patients were included. PVR was defined as a more than 1 log10 IU/mL decline in detectable serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR; ≥20 IU/mL) at week 48. A complete virologic response (CVR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL) at week 48. Results At week 48, the rate of the PVR was 64/227 (28.2%). Among patients with PVR, the cumulative rates of virologic response (serum HBV DNA <20 IU/mL) at weeks 96 and 144 were 45.2% and 73.8%, respectively. The cumulative rates of genotypic resistance were not significantly different between patients with a PVR and patients with a CVR (p=0.057). However, the cumulative rates of virologic breakthrough were higher in patients with PVR than in patients with CVR (4% vs 0% and 11.2% vs 0% at weeks 96 and 144, respectively; p<0.001). Conclusions Long-term continuous entecavir 0.5 mg treatment in patients with a PVR resulted in an additional virologic response without a significant increase in genotypic resistance. However, the rate of virologic breakthrough was higher in the partial responders.

Treatment Response and Tolerability of Pegylated Interferon-α Plus Ribavirin Combination Therapy in elderly Patients (≥ 65 years) With Chronic Hepatitis C in Korea.

Background The prevalence of hepatitis C virus (HCV) infections in elderly patients has been increasing in a number of countries. A few reports concerning pegylated interferon-α (PEG-IFN-α)-based combination treatment in elderly chronic hepatitis C (CHC) patients have been published, with slightly different treatment outcomes. Objectives We investigated the treatment response and safety of PEG-IFN-α plus ribavirin combination therapy in elderly patients with CHC. Patients and Methods Among a total of 181 treatment-naïve CHC patients (60 patients with genotype 1, 121 patients with genotype 2 or 3), 38 were aged ≥ 65 years (defined as the elderly group) and 143 were aged < 65 years (defined as the non-elderly group). Results The overall sustained virologic response (SVR) was lower in the elderly group than in the non-elderly group, but it was not significantly different (65.8 % vs. 76.2 %, P = 0.15). In a subgroup analysis, among patients with genotype 1, the elderly group had a significantly lower SVR rate than the non-elderly group (30.8 % vs. 66.0 %, P = 0.03). However, the SVR rate in patients with HCV genotype 2 or 3 was comparable between the two groups (84.0 % vs. 81.3 %, P = 0.85). HCV genotype was significantly associated with SVR in the elderly patients (genotype 1 vs. 2 or 3, odds ratio: 0.18, 95% confidence interval: 0.000-0.869, P = 0.03). The incidence of premature discontinuation of treatment (21.1 % vs. 9.1 %, P = 0.05) and dose modification (52.6 % vs. 31.5 %; P = 0.02) due mainly to adverse events or laboratory abnormalities, were higher in the elderly group than in the non-elderly group. Conclusions PEG-IFN-α plus ribavirin combination therapy might be considered for elderly CHC patients, especially for genotype 2 or 3, with vigilant monitoring of adverse events.

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

Background/Aims 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). Methods 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. Results 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). Conclusions 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.

Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Naïve Patients with Chronic Hepatitis B

Background/Aims Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated. Methods In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated. Results The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ≥6 log10 IU/mL (p=0.032) and detectable serum HBV DNA (≥12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients. Conclusions The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents.

A Case of Riata® Dual Coil Defibrillator Lead Failure in a Patient with Ventricular Fibrillation

A 50-year-old man, who underwent a procedure for an implantable cardioverter defibrillator (ICD), visited the outpatient department of our clinic after suffering multiple ICD shocks. The ICD interrogation revealed recurrent shock due to a high frequency of noise that is sensed by the device as ventricular fibrillation. Chest radiography revealed a significant split in the insulation of the lead allowing the inner wire to protrude. We considered the removal of the failed lead, but the removal of ICD lead is potentially a high risk procedure, so we cut and capped a proximal part of the failed lead and inserted a new lead. This is the first report of a St. Jude Riata® dual coil defibrillator lead failure with clinical and radiologic evidence of a defect in lead insulation in Korea.

C-terminal-truncated HBV X promotes hepato-oncogenesis through inhibition of tumor-suppressive β-catenin/BAMBI signaling

C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein. Ectopic ctHBx expression generated more colonies in anchorage-dependent and -independent growth assays than did HBx expression alone. ctHBx downregulated BAMBI to a greater degree than did HBx in HCC cells. HBx activated the Wnt/β-catenin pathway, which positively regulated the BAMBI expression through T-cell factor 1 signaling, whereas ctHBx negatively regulated the Wnt/β-catenin pathway. BAMBI downregulated the β-catenin and TGF-β1 signaling pathways. TGF-β1 positively regulated BAMBI expression thorough Smad3 signaling. Furthermore, knockdown of BAMBI was more tumorigenic in HCC cells. Therefore, downregulation of both β-catenin and TGF-β1 signaling by BAMBI might contribute to tumor suppression in mice xenotransplanted with HepG2 or SH-J1 cells. Taken together, ctHBx may have a more oncogenic role than HBx through its inhibition of tumor-suppressive β-catenin/BAMBI signaling.

Multiple ileal perforations due to regular diclofenac sodium injections: a case report

BackgroundAlthough the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the upper gastrointestinal tract have been well characterized, those specific to the lower gastrointestinal tract are less clear, as only a limited number of articles and case reports exist in the literature.Case presentationWe describe a case of a 69-year-old woman who presented to the emergency department due to sudden onset abdominal distension and pain. Notably, she reported using intramuscular diclofenac sodium twice daily for 14 days after knee joint replacement surgery. The patient denied any other coexisting diseases. As a subsequent X-ray and computed tomography (CT) scan showed free air in the abdomen, an exploratory laparotomy was performed, revealing four free perforations in the terminal ileum. Findings on microscopic analysis were non-specific.ConclusionWe report a unique case of multiple ileal perforations due to regular diclofenac sodium injections and contend that ileal perforation can be considered as a source for pneumoperitoneum with concomitant peritonitis in patients with a history of NSAID use if other possibilities are excluded.