Although hepatitis B infection is the major cause of chronic liver disease in Iran, no studies have employed economic evaluations of the medications used to treat Iranian patients with chronic hepatitis B (CHB). Therefore, the cost-effectiveness of the different treatment options for this disease in Iran is unknown.The aim of this study was to compare the cost utility and cost-effectiveness of medication strategies tailored to local conditions in patients with HB e antigen (HBeAg)-negative CHB infection in Iran.An economic evaluation of the cost utility of the following five oral medication strategies was conducted: adefovir (ADV), lamivudine (LAM), ADV + LAM, entecavir (ETV), and tenofovir (TDF). A Markov microsimulation model was used to estimate the clinical and economic outcomes over the course of the patient's lifetime and based on a societal perspective. Medical and nonmedical direct costs and indirect costs were included in the study and life-years gained (LYG) and quality-adjusted life-years (QALY) were determined as measures of effectiveness. The results are presented in terms of the incremental cost-effectiveness ratio (ICER) per QALY or LYG. The model consisted of nine stages of the disease. The transition probabilities for the movement between the different stages were based on clinical evidence and international expert opinion. A probabilistic sensitivity analysis (PSA) was used to measure the effects of uncertainty in the model parameters.The results revealed that the TDF treatment strategy was more effective and less costly than the other options. In addition, TDF had the highest QALY and LYG in the HBeAg-negative CHB patients, with 13.58 and 21.26 (discounted) in all comparisons. The PSA proved the robustness of the model results. The cost-effectiveness acceptability curves showed that TDF was the most cost-effective treatment in 59% - 78% of the simulations of HBeAg-negative patients, with WTP thresholds less than $14010 (maximum WTP per QALY).The use of TDF in patients with HBeAg-negative CHB seemed to be a highly cost-effective strategy. Compared with the other available medication options, TDF was the most cost-saving strategy. Thus, TDF may be the best option as a first-line medication. Patients can also be switched from other medications to TDF.
Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV therapy but there is little information about safety and efficacy of peginterferon alpha-2a and ribavirin combination therapy in these patients.In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 microg of Pegasys and 800-1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR).Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56-66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1-3.1), genotype non-1 OR=1.8 (95% CI 1.1-3.2), BMI<25 OR=2.1 (95% CI 1.3-3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1-3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation.Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients.
SUMMARY Background Hepatitis B is a significant health problem and more than 350 million individuals are infected with hepatitis B virus ( HBV ) globally. About 5% of these individuals are coinfected with hepatitis D virus ( HDV ). HBV–HDV coinfection increases the rate of fulminant hepatitis, chronic hepatitis and cirrhosis. This study aimed to evaluate the epidemiology of HDV in individuals positive for hepatitis B surface antigen ( HBsAg ) who were referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2012. Materials and Methods HBsAg ‐positive individuals attending this clinic were tested for anti‐HDAg antibodies (anti‐HDAbs). All samples positive for anti‐ HDAb were also tested for detection of HDV RNA by reverse transcription‐polymerase chain reaction (RT‐PCR). A questionnaire consisting of demographic characteristics and potential risk factors for acquisition of HDV was filled for each individual. Results Among 1038 individuals, HBsAg was detected in 660 (63·6%) cases following blood donation and in 378 (36·4%) cases following blood testing. In this study, 23 [2·2%, 95% confidence interval ( CI ) = 1·3–3·2%] patients were HDV ‐seropositive. In HDV ‐seropositive patients, 14 (60·9%, 95% CI = 39·1–78·3%) were positive for HDV RNA . HDV ‐seropositive cases were more likely to have evidence of severe forms of hepatitis than the group of individuals without anti‐ HDAb ( P < 0·01). Familial history of hepatitis D infection was more observed in HDV ‐seropositive patients than in individuals negative for anti‐ HDAb ( P < 0·01). Conclusion The seroprevalence of HDV in HBsAg ‐positive individuals in this study was about 2% which seems to be lower than the global prevalence of HDV .
Hepatitis B infection is still the main cause of chronic liver disease in Iran, which is associated with significant economic and social costs.This study aimed to estimate the financial burden caused by CHB infection and its complications in Iran.Prevalence-based and bottom-up approaches were used to collect the data. Data on direct medical costs were extracted from outpatient medical records in a referral gastroenterology and hepatology research center, inpatient medical records in several major hospitals in Tehran and Shiraz in 2013, and the self-reports of specialists. Data on direct non-medical and indirect costs were collected based on the patients' self-reports through face-to-face interviews performed in the mentioned centers. To calculate the indirect costs, friction cost approach was used. To calculate the total cost-of-illness in Iran, the total cost per patient at each stage of the disease was estimated and multiplied by the total number of patients.The total annual cost for the activate population of CHB patients and for those receiving treatment at various disease stages were respectively 450 million and 226 million dollars, with 64% and 70% of which allocated to direct costs respectively, and 36% and 30% to indirect costs respectively. The total direct costs alone for each group were respectively 1.17% and 0.6% of the total health expenditure. Furthermore, the cost spent on drugs encompasses the largest proportion of the direct medical cost for all stages of the disease.According to the perspectives of payers, patients, and community, CHB infection can be considered as one of the diseases with a substantial economic burden; the disease, specifically in extreme cases, can be too expensive and costly for patients. Therefore, patients should be protected against more severe stages of the disease through proper treatment and early diagnosis.
Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients.Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far.Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (≥ 50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n = 81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n = 199). Treatment experienced patients were eligible for this study.Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95 % CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8 %). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin.According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.
Scarce data is available on the efficacy of Pegylated Interferon (Peg-IFN) and Ribavirin (RBV) combination therapy in hemophilic children with chronic hepatitis C. The aim of this study was to evaluate the efficacy of Peg-IFN and RBV combination therapy for hemophilic children infected with hepatitis C virus (HCV) in comparison with adult hemophilic patients with chronic hepatitis C. A case-control study comprised 31 pediatric hemophilic patients ages under 16 years with previously untreated HCV genotype-1 or -3 infection as the case group and 62 treatment naive adult hemophilic patients with chronic HCV infection as the control group. Case and control groups were matched case by case according to HCV genotype, HCV RNA level and rs12979860 polymorphism. All patients in the case and control groups were treated with Peg-IFN and RBV for 24-48 weeks according to HCV genotype. Sustained virological response (SVR) was achieved in 26 (83.9%) pediatric patients and in 39 (62.9%) of adult patients (P = 0.05, OR = 3.07, 95%CI = 1.03-9.09). The rate of SVR was not different according to HCV genotype, HCV RNA level, and rs12979860 polymorphism in both studied groups whereas achieving early virological response was associated with achievement of SVR in both groups. The efficacy of Peg-IFN and RBV combination therapy in hemophilic children with chronic hepatitis C is higher than that of adult hemophilic patients.
Dear Editor,
The association of genetic factors with treatment induced hepatitis C clearance in Pakistani patients was recently demonstrated by Tipu et al. (1). They evaluated the impact of different genetic variants in interferon-λ (IFNL) genomic region on treatment induced hepatitis C clearance. The study was remarkable regarding the investigation of several numbers of single nucleotide polymorphisms (SNPs) in IFNL region. We would like to express our comments regarding the study. We observed that the patients in the study were treated with interferon (IFN) alpha 2b and ribavirin (RBV). Since the combination of pegylated IFN and RBV has been approved for treatment of chronic hepatitis C from 2002, the conventional regimen (IFN alpha 2b and RBV) for treatment of hepatitis C virus (HCV) infected patients is a debate point. Also, we have a concern regarding two terms through the article, first the authors defined the term sustained virologic response (SVR) as undetectable HCV RNA at the end of treatment course, whereas SVR must be defined as undetectable HCV RNA 24 weeks after treatment completion; second the term spontaneous clearance which refers to clearance of HCV from serum without treatment was misused through the article. Interestingly, the current study showed significant association between different IFNL polymorphisms and treatment response in HCV genotype 3 infected patients in our neighbor country (Pakistan). The results of previous studies searching for the association of IL28B SNPs and SVR in patients infected with HCV genotype 2/3 were conflicting and most of them did not find any association between IL28B SNPs and SVR (2, 3). Also, in this study, 50 SNPs were genotyped of which 25 of them were included in the final association analysis and 13 of them were found to be associated with the treatment response (1). The role of SNPs in the IFNL region remained mysterious and yet to be discovered. There are two main hypotheses for the role of these SNPs:
Combined effect of SNPs which refers to independent impact of each SNP;
Causal and Tag SNPs which is defined by the linkage disequilibrium (LD) between few tag SNPs and a causal SNP (sometimes undiscovered or untested).
Most of the SNPs in IFNL region including the SNPs found by Tipu et al. (1) to be associated with treatment response are in linkage disequilibrium (LD) which favors the Causal and Tag SNPs hypothesis. On the other hand, Prokunina-Olsson et al. (4) discovered a new IFNL gene which was assigned as IFNL4 and its encoded protein was observed to possess antiviral activity. Also, in the latter study, a genetic variant called ss469415590 (TT/ΔG) found to be located in exon one of IFNL4 gene which its TT allele does not express the protein and was associated with favorable treatment outcome and its ΔG allele expresses the IFNL4 protein and was associated with treatment nonresponse. The results of most previous studies looked for the functional role of IFNL SNPs showed the pretreatment expression of interferon stimulated genes (ISG) to be lower in patients with SVR when compared to patients with treatment failure. The same finding was observed for the expression of ISGs and IL28B genotypes in which the expression of ISGs were lower in patients with IFNL favorable genotypes than in patients with IFNL unfavorable genotypes (5, 6). However, the results of studies investigated the association of IL28B genotypes with IL28B expression were inconsistent which makes it difficult to draw the final role map (5-9). Discovery of IFNL4 gene and the exon one TT/ΔG SNP was a clue for solving the puzzle of IFNL genetic variations and HCV treatment response. If we accept the ss469415590 as the casual variant, the association of the IFNL genetic variants, IFNL4 expression, the subsequent ISGs expression, and the ultimate differences in treatment response seems to be relevant. In conclusion, studies such the one by Tipu et al. can open new horizons in diagnosis, management, and evaluation of hepatitis C prognosis in near future.
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