Can pegylated interferon α 2a cause development of thyroid disorders in patients with chronic hepatitis B?

Introduction: Hepatitis B virus infection is treated with pegylated (Peg) IFNα and nucleos(t)ide analogues. The disadvantages of PegIFNα include thyroid disorders. In this single-center study, the type, incidence and consequences of thyroid dysfunction in patients receiving PegIFNα due to chronic hepatitis B (CHB) were analyzed.

Patients and methods: The analysis included 106 patients (80 males) with CHB, aged 20 – 58 years, treated with PegIFNα-2a at a dose of 180 μg/week subcutaneously for 48 weeks. The levels of thyroid-stimulating hormone (TSH) and thyroid antibodies (TAbs) that is anti-thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies were measured in all patients at baseline. Furthermore, TSH was measured every 3 months during treatment and for 12 months after completion of treatment. If the TSH level was abnormal, free thyroxine 4 levels and TAbs were measured.

Results: All patients started the therapy with normal TSH and TAb levels. In 99 patients, TSH levels remained normal throughout the therapy. Thyroid disorder occurred in seven patients (6.6%), six of whom developed hypothyroidism and one who developed hyperthyroidism. Thyroid dysfunction was diagnosed in six women and one man. TAbs (only TPOAbs) were found in two patients (1.88%).

Conclusions: Thyroid disorder is a rare, though possible not transient, complication of IFN therapy in CHB patients.     

Treatment of chronic hepatitis C in children with pegylated interferon α2a and ribavirin--a multi-center study

Pegylated interferon α and ribavirin in treatment of chronic hepatitis C in children is used rarely. The aim of the study was to find prognostic factors for sustained virological response and to analyze the safety of pegylated interferon α2a and ribavirin in children with chronic hepatitis C. The study covered a group of 44 children, mean age 14 years, with diagnosed chronic hepatitis C. Clinical, biochemical and virological parameters, as well as side effects were evaluated. Combined treatment allowed to obtain sustained virological response in a total of 77.5% of the treated children. Lower viral load and lower fibrosis grade contributed to sustained virological response. The response was not gender-related. The best response is obtained in children whose treatment was started after they attained the age of 10 years. Therapy with pegylated interferon α2a and ribavirin is well tolerated by pediatric patients.     

Supervised conventional interferon α2a in combination with ribavirin therapy is the preferred alternative for treatment of chronic hepatitis C

Objective:

To document the significant sustained virological response with supervised conventional interferon α and ribavirin therapy in hepatitis C virus (HCV)-infected patients, this study was planned.

Materials and Methods:

Sixty chronic hepatitis C naive patients were included in this study. Complete blood counts, prothrombin time, ALT, AST, and qualitative HCV RNA were done. Conventional interferon (INF) α2a, 3MIU, S.C and ribavirin 1000 mg PO was given as supervised therapy for 24 weeks in genotype 3 and 48 weeks in genotype 1 and 4 HCV patients. Qualitative HCV RNA was repeated at 12 weeks, 24 weeks for HCV infections with genotype 1, 2, 3 and 4, at 48 weeks for genotype 1 and 4, and thereafter 6 months after completion of treatment. End virological and sustained virological responses were observed.

Results:

Out of 60 patients, 55 completed the study. Five patients were lost to follow-up. Overall SVR was seen in 47 patients (85.4%) and 4 patients had relapses.

Conclusion:

Significant sustained virological response rates were seen in patients with supervised conventional INF α2a and ribavirin therapy.KEY WORDS: Conventional interferon, hepatitis C, ribavirin, supervised     

Benefits of long-term therapy with nucleos(t)ide analogues in treatment-naïve patients with chronic hepatitis B

Objective: To assess the benefits of long-term nucleos(t)ide analogue (NA) therapy in reducing the severity and progression of liver disease in treatment-naïve patients with chronic hepatitis B (CHB).

Scope: As complications of CHB, such as hepatic decompensation and hepatocellular carcinoma (HCC), take a long time to develop in patients with less advanced disease, the long-term benefits of NA therapy in such patients are more difficult to prove than short- or medium-term benefits. Thus, the recent literature was reviewed to evaluate the impact of NA therapy on the long-term outcomes of treatment-naïve CHB patients.

Methods: A literature search of the MEDLINE/PubMed database was undertaken to identify studies published since 2010 of the long-term use of NAs with high potency and low drug resistance profiles in treatment-naïve CHB patients. A total of 22 studies were identified, many of which were retrospective analyses or case–control studies, as well as three meta-analyses and one systematic review.

Results: Analysis of the retrieved studies showed that long-term NA therapy in treatment-naïve CHB patients did prevent or delay the occurrence of complications, including hepatic decompensation, HCC, and liver-related death, in comparison with no treatment. However, it did not completely eliminate the risk of these complications, particularly in those with cirrhosis. Although long-term NA therapy improved the clinical status of patients with decompensated cirrhosis, the risk of cirrhotic complications including HCC, liver transplantation, and liver-related mortality remained significant in comparison with those with compensated cirrhosis.

Conclusions: Long-term administration is generally advised in all CHB patients treated with NAs because of the high rates of virological and clinical relapse after stopping therapy. The findings of this analysis lend support to the choice of highly potent agents with a low drug resistance profile to maximize viral suppression in CHB patients and halt or delay progression to end-stage liver disease.     

Induction interferon therapy in naïve patients with chronic hepatitis C: increased end-of-treatment virological responses but absence of long-term benefit

BACKGROUND AND AIMS: The low efficacy of interferon monotherapy and data from viral kinetic studies led us to evaluate the efficacy of interferon administered daily in chronic hepatitis C. PATIENTS AND METHODS: Thirty-eight na?ve patients with chronic hepatitis C and active liver disease randomly received 3 or 5 MU IFN-alpha daily for 1 month, followed by the same dose three times a week for 11 months. Results were compared to a three-times-a-week scheme of 3 MU IFN-alpha for 1 year. RESULTS: At the end of the induction period, 27 out of 38 (71%) patients had cleared HCV-RNA with a significantly higher rate in the 5 MU than in the 3 MU group (17 out of 18 or 94% vs. 10 out of 20 or 50%, P=0.003). The end-of-treatment virological response rate was 66% (25 out of 38) in the induction groups and 40% (10 out of 25) in the control group (P=0.04). Six months after completion of therapy, the sustained response rate dropped to 29% (11 out of 38) compared to 28% (7 out of 25) in the standard regimen. CONCLUSIONS: In chronic hepatitis C, treatment with 5 or 3 MU IFN-alpha daily during the first month of a standard IFN regimen leads to significantly increased end-of-treatment virological responses, but long-term responses are similar to those of standard IFN monotherapy.     

Therapeutic effects of KANK2 in myocardial infarction rats might be associated with the NF-κB p65 inhibition

ObjectiveKN motif and ankyrin repeat domains 2 (KANK2) may inhibit the activation of (NF-kappaB) p65, which plays a role in myocardial injury. Thus, our study aims to discover the effect of KANK2 on myocardial infarction (MI) induced by ligating the left anterior descending coronary artery (LAD) through regulating NF-κB p65 in vivo.MethodsMI rats underwent LAD ligation were administered with intramyocardial injections of KANK2/Control activation plasmids. Six weeks after MI, pressure-volume (P/V) loops was used to investigate the cardiac function of rats, then the following detections were performed, including TTC staining, HE staining, immunofluorescence, Masson’ s trichrome staining, ELISA assay, TUNEL staining, immunohistochemistry, qRT-PCR and Western blotting.ResultsMI rats decreased in maximum pressure (p_max), ejection fraction (EF%), peak rate of pressure rise (dpdt_max) and decline (-dpdt_max) with increased end diastolic pressure (EDP), which was partially reversed by KANK2 overexpression. Besides, KANK2 CRISPR activation plasmids reduced infarct size with less collagen fiber proliferation and neutrophil infiltration in infarct tissues, as well as suppressed pro-inflammatory factors expressions in MI rats. Moreover, injection of KANK2 activation plasmid decreased collagen deposition, aggravated cardiomyocyte apoptosis, enhanced the capillary density, and increased the expressions of VEGF and bFGF in the infarct and peri-infarct regions of MI rats. KANK2 lowered myocardial NF-κB p65 expression in MI rats.ConclusionKANK2 may play its therapeutic role in MI through improving cardiac function, decreasing myocardial collagen deposition, reducing cardiomyocyte apoptosis, and increasing angiogenesis, which might be associated with the reduction of NF-κB p65 expression.     

Safety and efficacy of glecaprevir/pibrentasvir in patients with chronic hepatitis C genotypes 1–6 receiving opioid substitution therapy

BackgroundInternational guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.MethodsPooled data from patients with HCV genotypes 1–6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.ResultsAmong 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2–99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3–98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.ConclusionGlecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST.     

High-dose interferon alpha-2a with ribavirin and amantadine in naïve chronic hepatitis C patients--results of a randomized,prospective, pilot study

BACKGROUND: Hepatitis C viral kinetic studies have demonstrated the increased anti-viral effect of higher than standard dosages of interferon and of daily treatment schedules. AIM: To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high-dose interferon-alpha therapy vs. standard-dosage interferon-alpha therapy, in a triple therapy combination with ribavirin and amantadine. METHODS: Previously untreated patients with chronic hepatitis C were randomized to the standard interferon-alpha group (n = 15), receiving thrice weekly 6 MU interferon-alpha for 12 weeks, followed by 3 MU interferon-alpha for 36 weeks, or the high-dose interferon-alpha group (n = 15), receiving daily 9 MU interferon-alpha for 4 weeks, followed by 6 MU (weeks 5-8), 3 MU (weeks 9-12) and 1.5 MU (weeks 13-48) interferon-alpha. All patients were given ribavirin (1000-1200 mg) and amantadine (200 mg) daily for 48 weeks. RESULTS: At the end of treatment and after the 24-week follow-up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard-dosage interferon-alpha, respectively, compared with 11 (73%) and 10 (67%) treated with high-dose interferon-alpha, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons. CONCLUSIONS: The findings suggest that, although the difference between the response rates of standard and high-dose interferon-alpha regimens (within a triple anti-viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high-dose interferon-alpha therapy and an equal safety profile.     

The combination of ınterleukin-10 -1082 and tumor necrosis factor α -308 or ınterleukin-6 -174 genes polymorphisms suggests an association with susceptibility to Hashimoto's thyroiditis

BackgroundThe etiopathogenesis of Hashimoto's thyroiditis (HT) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. The imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with HT, and to evaluate the relationship between genotypes and clinical/laboratory manifestation of HT.MethodsTumor necrosis factor α (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 G-1082A (rs 1800896) single nucleotide polymorphisms (SNPs) in DNA from peripheral blood leukocytes of 190 patients with HT and 231 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes.ResultsThere was no notable risk for HT afflicted by TNFα ? 308, IL-6 ? 174 and IL-10 ? 1082 polymorphisms alone. However, carriers of variant alleles of both IL-10 ? 1082 and TNFα ? 308 polymorphisms had four-fold times higher risk for HT in comparison with non-carriers. Additionally, concomitant presence of both mutant IL-10 ? 1082 A and IL-6 ? 174 C alleles raised three-fold the HT risk.ConclusionOur results suggest that the combined effects of TNFα ? 308, IL-6 ? 174 and IL-10 ? 1082 variant alleles may be more decisive to induce functional differences and modify the risk for HT.