Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.
Antiviral Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/etiology ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon-alpha/adverse effects/therapeutic use ; Liver Cirrhosis/complications ; Liver Neoplasms/etiology ; Nucleotides/adverse effects/chemistry/therapeutic use ; Risk Factors

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.
Amylases/analysis ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnostic imaging/*drug therapy ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Lipase/analysis ; Middle Aged ; Pancreatitis/*etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; Recombinant Proteins/adverse effects/therapeutic use ; Republic of Korea ; Ribavirin/therapeutic use ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.
Adult ; Aged ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemophilia A/*complications ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Liver/pathology ; Male ; Middle Aged ; Neutropenia/etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; RNA, Viral/blood ; Recombinant Proteins/adverse effects/therapeutic use ; Recurrence ; Republic of Korea ; Ribavirin/adverse effects/*therapeutic use ; Treatment Outcome

Aged, 80 and over ; Carcinoma, Renal Cell ; drug therapy ; Female ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Interleukin-2 ; adverse effects ; therapeutic use ; Lung Diseases, Interstitial ; chemically induced ; diagnosis ; Recombinant Proteins ; adverse effects ; therapeutic use

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.
Antifungal Agents/therapeutic use ; Antiviral Agents/*adverse effects ; Cryptococcus neoformans/immunology/*pathogenicity ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnosis/*drug therapy/immunology ; Humans ; Immunocompromised Host ; Interferon-alpha/*adverse effects ; Meningitis, Cryptococcal/drug therapy/immunology/*microbiology ; Middle Aged ; Opportunistic Infections/diagnosis/drug therapy/immunology/*microbiology ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Ribavirin/*adverse effects ; Time Factors ; Treatment Outcome

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFalpha) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFalpha inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFalpha therapy in patients with TNFalpha-associated TB. We used data of 1,012 patients with RA or AS treated with TNFalpha inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-gamma releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFalpha therapy. All patients discontinued TNFalpha inhibitors with starting the treatment of TB. Eight patients were re-administered TNFalpha inhibitors due to disease flares and promptly improved without recurrence of TB. TNFalpha inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Humans ; Hydroxychloroquine/adverse effects/therapeutic use ; Immunoglobulin G/adverse effects/therapeutic use ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Interferon-gamma Release Tests ; Male ; Methotrexate/adverse effects/therapeutic use ; Middle Aged ; Mycobacterium tuberculosis/isolation & purification ; Receptors, Tumor Necrosis Factor/therapeutic use ; Retrospective Studies ; Spondylitis, Ankylosing/*drug therapy ; Tuberculin Test ; Tuberculosis/*chemically induced/microbiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFalpha and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFalpha, including type and treatment duration. The median duration of anti-TNFalpha was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFalpha in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFalpha.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/*adverse effects/*therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Female ; Follow-Up Studies ; Humans ; Interferon-gamma/*blood ; Latent Tuberculosis/*blood/*chemically induced/diagnosis ; Longitudinal Studies ; Male ; Middle Aged ; Prognosis ; Reproducibility of Results ; Sensitivity and Specificity ; Spondylitis, Ankylosing/blood/*drug therapy ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

BACKGROUND/AIMS: Individuals being treated with tumor necrosis factor (TNF)-alpha inhibitors are at increased risk of developing tuberculosis (TB). We determined the clinical characteristics and treatment response of patients who developed TB after using TNF-alpha inhibitors. METHODS: Patients with TB detected within 12 months of the initiation of TNF-alpha inhibitor treatment were included, if seen from January 1, 2000 to August 31, 2011. We retrospectively reviewed the clinical records, results of bacteriological examinations, and radiographs of the included patients and the response to anti-TB treatment. RESULTS: We indentified seven cases of TB in 457 patients treated with TNF-alpha inhibitors during the study period. TB developed a median of 123 days (range, 48 to 331) after the first dose of TNF-alpha inhibitor. Pulmonary TB, including TB pleuritis, was diagnosed in three patients and extrapulmonary TB in four. Favorable treatment outcomes were achieved in six of seven patients. CONCLUSIONS: Among the TNF-alpha inhibitor users who contracted TB, extrapulmonary sites were common and the treatment response was satisfactory.
Adult ; Aged ; Antitubercular Agents/therapeutic use ; Female ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/*adverse effects ; Interferon-gamma Release Tests ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tuberculin Test ; Tuberculosis/diagnosis/drug therapy/*immunology/microbiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

OBJECTIVETo confirm the efficacy and safety of Jitongning Capsule in the treatment of ankylosing spondylitis (AS).

METHODSA total of 120 AS patients with early-intermediate were randomly and equally assigned to Jitongning Capsule group and sulfasalazine group. Jitongning Capsule was orally taken 4.5 g per day and sulfasalazine was orally taken 2 g daily for 12 months. The primary endpoint was the proportion of patients achieving the Assessment in Ankylosing Spondylitis 20 (ASAS 20), secondary end points included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), patient's global assessment by VAS rating, spinal pain, general pain and night pain, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMC) of AS patients were measured.

RESULTSA total of 111 patients completed the study. There were 58 patients in Jitongning group and 53 patients in sulfasalazine group. Both drugs showed mild and occasional side effects. After treated by Jitongning Capsule and sulfasalazine, the proportion of ASAS20 responders at 12 month was 72.41% (42/58) and 67.92% (36/53) respectively. Both Jitongning Capsule and sulfasalazine treatment induced significant decrease in the proportion of CD4(+)T cell and CD8(+)T cell expressing TNF-&alpha; and IFN-γ at 12-month of treatment compared with baseline values (P<0.05).

CONCLUSIONJitongning Capsule are effective in a setting close to real-life medical care with a sustained improvement in signs and symptoms of AS, and reduce cytokine levels in PBMC. It showed comparable effects to sulfasalazine.

Adult ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; CD4-Positive T-Lymphocytes ; drug effects ; secretion ; CD8-Positive T-Lymphocytes ; drug effects ; secretion ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Endpoint Determination ; Female ; Flow Cytometry ; Humans ; Interferon-gamma ; secretion ; Interleukin-4 ; secretion ; Male ; Middle Aged ; Spondylitis, Ankylosing ; blood ; drug therapy ; immunology ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; secretion ; Young Adult

OBJECTIVETo compare the efficacy and safety of the common antivirals, including adefovir dipivoxil (ADV), pegylated-interferon alpha-2a (peg-IFN) and lamivudine (LAM), used as combination therapies to treat chronic hepatitis B (CHB) patients with positivity for the hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) harboring the ADV-resistance mutation, rtN236T, and to explore the factors associated with curative outcome.

METHODSSixty-five adult CHB patients (age range: 20-60 years) who were unresponsive to ADV therapy (HBeAg-positive; HBV DNA >or= 10(5) copies/ml), LAM-naive, and tested positive for the rtN236T HBV mutation were enrolled in the study and randomly divided into two treatment groups: Group A (n = 33), who were administered ADV (10 mg/day, orally) plus peg-IFN (180 microg/week, subcutaneous injection) for 48 weeks; and Group B (n = 32 patients), who received the ADV plus LAM (100 mg/day, orally) for 48 weeks followed by continued LAM treatment for an additional 24 weeks. Pre- (baseline), during and post-treatment measurements of HBV viral loads and hepatitis B markers were made by quantitative PCR and electrochemiluminescence assays, respectively. All patients underwent liver biopsies to determine the histological activity index (HAI) and treatment response regarding inflammation and fibrosis stage. The rates of virological response (VR), HBeAg-negativity, HBeAg seroconversion, and alanine aminotransferase (ALT) normalization were calculated, and the significance of differences between groups were assessed by Student's t-test and Chi2 test.

RESULTSThere were no significant differences between the two groups in regards to sex, age, or baseline levels of HBV DNA, ALT, and total bilirubin (P > 0.05). At weeks 24 and 48 of treatment and 24 after treatment end, group A showed significantly higher (vs. group B, P < 0.05) rates of reduced HBV DNA viral loads (81.8%, 90.9%, and 75.8% vs. 53.1%, 56.2%, and 59.4%), VR (48.5%, 60.6%, and 42.4% vs. 31.3%, 34.4%, and 31.3%), HBeAg-negativity (39.4%, 60.6%, and 54.5% vs. 12.5%, 37.5%, and 37.5%), HBeAg seroconversion (27.3%, 54.5%, and 48.5% vs. 6.3%, 15.6%, and 18.8%), and ALT normalization (72.7%, 84.8%, and 78.8% vs. 46.9%, 56.3%, and 46.9%). After 48 weeks of treatment, group A showed significantly improved HAI (vs. group B, P < 0.05). With the exception of treatment-related increased creatinine (P < 0.05), group A showed significantly higher rates of adverse reactions; although, none was serious enough to threaten patient safety or necessitate early termination of the treatment regimen. Twenty-four weeks after treatment completion, five patients had HBV viral loads of >or= 2log10 copies/ml and four had < or= 500 copies/ml, and ALT was normalized in 28 patients. The four patients in group A with HBV DNA < or= 500 copies/ml and elevated ALT during treatment did not show HBeAg seroconversion.

CONCLUSIONPeg-IFN plus ADV combination therapy produced better outcomes than the ADV plus LAM combination therapy in regards to HBV viral loads, VR rate, HBeAg-negative rate, HBeAg seroconversion rate, ALT normalization rate, and HAI, but was associated with a higher rate of adverse reactions (none of which were severe). Lack of HBeAg seroconversion was associated with higher virus load and ALT levels.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Drug Resistance, Viral ; genetics ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Lamivudine ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Mutation ; Organophosphonates ; adverse effects ; therapeutic use ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Recombinant Proteins ; adverse effects ; therapeutic use ; Young Adult