Entecavir (Baraclude®) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy.
Administration, Oral ; Antiviral Agents/*adverse effects/therapeutic use ; Brain/diagnostic imaging ; Drug Therapy, Combination ; Duloxetine Hydrochloride/therapeutic use ; Glucocorticoids/therapeutic use ; Guanine/adverse effects/*analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/drug therapy ; Humans ; Male ; Middle Aged ; Polyneuropathies/*diagnosis/drug therapy/etiology ; Prednisolone/therapeutic use ; Pregabalin/therapeutic use ; Tomography, X-Ray Computed

BACKGROUND/AIMS: The aim of this study was to evaluate the estimated glomerular filtration rate (eGFR) during telbivudine (LdT) versus entecavir (ETV) treatment in chronic hepatitis B (CHB) patients with underlying comorbidities such as diabetes mellitus (DM), hypertension, and cirrhosis. METHODS: From 2010 to 2012, 116 CHB patients treated with LdT and 578 treated with ETV were compared in this real-practice cohort. The mean changes in eGFR (Modification of Diet in Renal Disease [MDRD] formula) from baseline to months 6, 12, and 18 were analyzed using a linear mixed model. RESULTS: In LdT-treated patients, the mean eGFR increased by 7.6% at month 18 compared with the eGFR at baseline (MDRD formula in mL/min/1.73 m2). However, in ETV-treated patients, the mean eGFR decreased by 4.1% at month 18 compared with the eGFR at baseline. In the LdT-treated patients with DM, hypertension, cirrhosis or low eGFR <90 mL/min/1.73 m2, the mean eGFR showed a steady improvement, whereas the mean eGFR was reduced in the same subgroups of ETV-treated patients. CONCLUSIONS: The eGFR gradually increased over time during LdT treatment, especially in patients with mild abnormal eGFR at baseline, and in those with DM, hypertension, and cirrhosis, whereas a reduction in eGFR was seen with ETV treatment.
Adult ; Antiviral Agents/*administration & dosage ; Diabetes Complications ; Diabetes Mellitus ; Drug Administration Schedule ; Female ; Fibrosis/complications ; Glomerular Filtration Rate/*drug effects ; Guanine/administration & dosage/*analogs & derivatives ; Hepatitis B, Chronic/complications/*drug therapy/physiopathology ; Humans ; Hypertension/complications ; Linear Models ; Male ; Middle Aged ; Thymidine/administration & dosage/*analogs & derivatives ; Time Factors ; Treatment Outcome

BACKGROUND/AIMS: The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined . The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naive chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy. METHODS: This study included 364 treatment-naive CHB patients treated with ETV for > or =48 weeks and who received continuous ETV monotherapy for > or =96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log10 IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48. RESULTS: Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for > or =96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up. CONCLUSIONS: Long-term ETV monotherapy is effective for achieving a VR in treatment-naive CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Administration Schedule ; Female ; Genotype ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy/pathology/virology ; Humans ; Liver Cirrhosis/etiology/radiography/ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Female ; Glutamates ; administration & dosage ; Guanine ; administration & dosage ; analogs & derivatives ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Neoplasm Metastasis ; Pemetrexed ; Quinazolines ; administration & dosage ; Stevens-Johnson Syndrome ; etiology

PURPOSE: We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. MATERIALS AND METHODS: Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. RESULTS: Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. CONCLUSIONS: Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.
Administration, Oral ; Animals ; Antioxidants ; Fibrosis ; Guanosine Monophosphate ; Humans ; Hypogonadism ; Leuprolide ; Male ; Neurons ; Nitric Oxide ; Nitric Oxide Synthase ; Oxidative Stress ; Phytotherapy ; Rats* ; Rho Guanine Nucleotide Exchange Factors ; Superoxide Dismutase ; Testosterone ; Urinary Bladder* ; Water

OBJECTIVETo explore the efficacy and safety of pemetrexed in the treatment of relapsed primary central nervous system lymphoma (PCNSL).

METHODSSeven cases with relapsed PCNSL admitted in our hospital between August 2012 and August 2013 were retrospectively reviewed.

RESULTSOf the 7 relapsed cases, ectopic recurrence occurred in 3, in situ recurrence in 3 and leptomeningeal metastasis in 1. Patients with relapsed PCNSL were administered with high-dose pemetrexed (900 mg/m²) once for every 3 weeks and supplemented with folic acid and vitamin B₁₂. Complete remission was obtained in 2 patients, partial remission in 3 patients and progressive disease in 2. The overall response rate was 71.4% (5/7). The main adverse reactions were myelosuppression and gastrointestinal reaction.

CONCLUSIONTreatment of relapsed PCNSL is difficult, and its prognosis is very poor. Pemetrexed therapy is a meaningful trial.

Adult ; Aged ; Central Nervous System Neoplasms ; drug therapy ; pathology ; Female ; Glutamates ; administration & dosage ; adverse effects ; therapeutic use ; Guanine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Pemetrexed ; Prognosis ; Retrospective Studies

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Calbindin 2 ; metabolism ; Cholecystitis ; pathology ; Cisplatin ; administration & dosage ; Cystitis ; pathology ; Diagnosis, Differential ; Female ; Glutamates ; administration & dosage ; Guanine ; administration & dosage ; analogs & derivatives ; Humans ; Inflammation ; pathology ; Keratins ; metabolism ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Mesothelioma ; drug therapy ; metabolism ; pathology ; surgery ; Middle Aged ; Pemetrexed ; Peritoneal Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Survival Rate ; Vimentin ; metabolism

OBJECTIVETo observe the clinical efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer (NSCLC).

METHODSSeventy patients aged 70 years or over with stage IIIb-IV NSCLC were equally and randomly divided into pemetrexed plus cisplatin group (PC) and gemcitabine plus carboplatin group (GC). Patients in the PC group received pemetrexed (PEM) 500 mg/m(2) on day 1, and carboplatin (CBP) AUC5 on day 1 for 21-day cycle. Patients in the GC group received gemcitabine 1000 mg/m(2) on days 1 and 8, CBP AUC5 on day 1 for a 21-day cycle.

RESULTSIn the PC and GC groups, CR 0 and 0, PR 10 and 8, response rates 28.6% and 22.9% were observed, respectively. There was no statistically significant difference between the two groups (χ(2) = 0.299, P = 0.584). The 1-year and 2-year survival rates of the PC and GC groups were 48.6% vs. 45.7% and 11.4% vs. 11.4%, respectively, with a median survival of 11.00 and 10.00 months, without a statistically significant difference between the two groups (χ(2) = 0.01, P = 0.919). Regarding toxicities, the incidences of neutropenia/thrombocytopenia, nausea and vomiting (grade III ∼ IV) in the GC group were significantly higher than those in the PC group (P < 0.05). According to the observer scale of lung cancer symptoms, the post-treatment scores improved in both the two groups, and with no significant difference between them (P > 0.05).

CONCLUSIONSPC and GC show similar efficacy for elderly NSCLC patients, however, the toxicities in PC patients are lower than those in GC patients. Thus, pemetrexed combined with carboplatin is an effective chemotherapeutic regimen for advanced NSCLC in elderly patients.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Follow-Up Studies ; Glutamates ; administration & dosage ; Guanine ; administration & dosage ; analogs & derivatives ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Pemetrexed ; Quality of Life ; Survival Rate ; Thrombocytopenia ; chemically induced ; Vomiting ; chemically induced

BACKGROUND/AIMS: We investigated the efficacy of continuous long-term entecavir 0.5 mg treatment in naive 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; > or =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.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*administration & dosage ; DNA, Viral/*blood ; Drug Resistance, Viral/genetics ; Female ; Guanine/administration & dosage/*analogs & derivatives ; Hepatitis B e Antigens/blood ; *Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Viral Load

OBJECTIVETo investigate the efficacy and safety of peginterferon alfa-2a (Peg-IFNa-2a) therapy for treating chronic hepatitis B (CHB) in patients who failed to achieve a satisfactory end point with entecavir (ETV) treatment.

METHODSFifty-seven CHB patients with positivity for hepatitis B e antigen (HBeAg) who had completed a standard ETV monotherapy course, of at least 96 weeks, and who had achieved a virological response (defined as HBV DNA less than 500 copies/ml) but without HBeAg seroconversion (defined as 0.227 PEI U/ml less than HBeAg less than or equal to 50 PEI U/ml) were enrolled in the study. The patients were randomly assigned to receive a 48-week treatment with Peg -IFNa-2a (experimental group, n = 27) or continued ETV therapy (control group, n = 30). Serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. Inter-group differences were statistically evaluated by t-test or Chi-squared test.

RESULTSThe baseline levels of alanine aminotransferase, hepatitis B surface antigen (HBsAg), and HBeAg were similar between the patients comprising the experimental and controls groups. At treatment week 48, the experimental group showed significantly higher rates of HBeAg clearance (Peg-IFNa-2a: 40.7% vs. ETV: 16.7%, x2 = 4.079, P less than 0.05) and seroconversion (37.0% vs. 13.3%, x2 = 5.110, P less than 0.05). The experimental group also showed higher rates of HBsAg clearance (7.4% vs. 0%) and HBV DNA relapse (11.1% vs. 0%), but the differences did not reach statistical significance (x2 = 2.307 and 3.519, both P more than 0.05). However, the level of HBsAg was significantly lower in the experimental group (2866.0+2580.4 vs. 4335.8+2650.0 IU/ml, t = 5.11, P less than 0.05).

CONCLUSIONHBeAg-positive CHB patients with unsatisfactory response to initial ETV monotherapy achieved HBeAg seroconversion and clearance following sequential Peg-IFN a-2a treatment.

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Prospective Studies ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult