Side Effects Of Antiviral Therapy Research Articles

Efficacy and safety of direct-acting antiviral therapy in previous hard-to-treat patients with recurrent hepatitis C virus infection after liver transplantation: a real-world cohort.

BackgroundRecurrent hepatitis C virus (HCV) infection after liver transplantation (LT) has been a frequent and relevant problem in the past two decades. This analysis evaluated the efficacy and safety of new interferon (IFN)-free direct-acting antiviral (DAA) therapies in a large real-world cohort of HCV patients after LT.MethodsWe retrospectively analyzed a cohort of 157 patients infected with HCV who underwent deceased donor LT between 1997 and 2014. Patient survival, outcome, and side effects of antiviral therapy were assessed.ResultsSurvival with recurrent HCV genotype 1 (GT1) infection was inferior to other HCV GTs (P=0.01). The overall sustained virological response (SVR) rate with new DAA therapy was 94.6% (n=37). Patients with both GT1 and other GTs reached SVR rates >90%. We noticed a few side effects, mainly caused by ribavirin, and only one discontinuation in DAA-treated patients.ConclusionDAA therapy was effective and safe in previous hard-to-treat patients after LT in this real-world cohort.

HIV INFECTION STAGE, ANTIRETROVIRAL THERAPY SCHEME AND PATIENT IMMUNE STATUS INFLUENCE ON HIV/TB CO-INFECTION OUTCOME

Retrospective research of 381 clinical records is conducted to study HIV infection influence on stationary stage of tuberculosis treatment outcome in HIV-TB co-infected patients. All cases were divided depending on a hospitalization outcome on favorable and adverse. At most of patients tuberculosis of respiratory organs met. Immunological researches were conducted, the stage of HIV infection was registered and the issue of purpose of anti-retroviral therapy was resolved. Besides, as indirect signs of an immunodeficiency at the patients with a combination of tuberculosis and HIV infection who were on hospitalization the indicators received when carrying out clinical laboratory trials were analyzed: absolute and relative quantity of lymphocytes according to the general blood test, the contents the globulin fractions and circulating immune complexes concentration according to the clinical chemistry blood test. At an assessment of results in both groups of research more than at a half of patients existence of HIV infection at late stages that speaks about late identification and neglect of an immunodeficiency was revealed. At patients with tuberculosis of lungs in combination with HIV infection at a failure statistically significant decrease in an immunoregulatory index is revealed. It is interesting that the level of CD4 lymphocytes and a stage of HIV infection had no impact on the co-infection’s outcome. However, existence of virus loa ding more than 100 000 copies/ml reduced probability favorable an outcome of treatment of tuberculosis at the patient with HIV infection. Timely purpose of anti-retroviral therapy at patients with co-infection increased chances of treatment of tuberculosis at patients with an immunodeficiency. Frequency of adverse side effect of antiviral therapy met equally often at patients in both groups. Thus, patients at any stages of HIV infection with any forms of tuberculosis, including generalized, had a chance to have a favorable outcome of a disease. We consider the reasonable recommendation about carrying out anti-retroviral therapy of patients by all with a combination of tuberculosis and HIV infection, irrespective of the HIV infection stage.

HLA-C and KIR combined genotype as new response marker for HBeAg-positive chronic hepatitis B patients treated with interferon-based combination therapy.

Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir. Genotyping of killer immunoglobin-like receptors (KIRs) was performed by SSP-PCR. One SNP in HLA-C (rs2308557) was significantly associated with combined response in HBeAg-positive CHB patients (P = 0.003). This SNP is linked to the HLA-C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA-C2 was observed significantly more often in HBeAg-positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1-C2 predicted response independent of HBV genotype and ALT at baseline. HLA-C and KIR genotype is strongly associated with response in HBeAg-positive CHB patients treated with interferon-based therapy. In combination with other known response markers, HLA-C/KIR genotype could enable the selection of patients more likely to respond to interferon-based therapy.

Cytokines Polymorphism and mRNA Expression as Biomarkers in HCV Treatment Response

Background: Hepatitis C virus is a serious global health problem affecting more than 170 million patients who are at risk of developing liver cirrhosis and/or hepatocellular carcinoma. Egypt has the highest prevalence of HCV (genotype 4) as about 14.7% of Egyptian populations are positive for HCV antibodies. Aim: To review recent data and patents concerning cytokine polymorphism that affect the likelihood of achieving SVR and can be used as biomarkers for predicting the treatment response to overcome the unnecessary cost, time, and side effects of antiviral therapy for nonresponders. Methods: Data were pooled from 36 studies carried out internationally in which patients with chronic HCV receiving PEG IFN/RBV therapy were evaluated regarding cytokine polymorphism and/or its mRNA expression profile in relation to therapy response. Results and Conclusions: Studies to date have shown that cytokine gene polymorphism plays an important role in the natural clearance of HCV. Most of polymorphisms are in cytokine gene regulatory regions and are consequently involved directly in controlling the transcription rates. Type 1-like cytokines, such as IL-1β, IL-2, IL-6, IL-18, TNF-α, and IFN-γ were up-regulated in chronic HCV infection. The poor response was found to be associated with high producing genotype of IL-10, up-regulation of IL-28B and most of IGS genes, and associated with downregulation of TGF- β, IFN-γ. Good response was noticed to be associated with high level IL-6, IL-8, and certain genotypes of IL-6, IL-12, IFN-γ, TNF-α IFN λ4 and IFN λ3. Keywords: Antiviral therapy, cytokines, HCV, interleukins, ISG, polymorphism.

OC.07.6 ITALIAN MULTICENTER STUDY ON INFLAMMATORY BOWEL DISEASES WITH HBV OR HCV INFECTION UNDERGOING IMMUNOSUPPRESSIVE THERAPY

Background and aim: Digestive symptoms are common side effects of antiviral therapy in patients with HCV chronic hepatitis (CH). The occurrence of digestive symptoms significantly impairs quality of life and requires reduction or even suspension of the therapy in up to 15% of the cases. Recent advances in pathophisiology of functional dyspepsia indicate that delay of gastric emptying time (GET) likely depending on altered Cholecystokinin (CCK) and Motilin serum levels is implicated in the onset of symptoms. In this study we evaluated digestive symptoms, GET and CCK and motilin fasting and post-prandial serum levels in patients with HCV-related CH before, during and after standard antiviral therapy. Material and methods: Twenty-eight patients (M/F 11/17 male, age range 28-70 yrs) with histologically proven HCV-related CH and absence of digestive diseases were enrolled in the study. Baseline, during the therapy (3th month) and after a month by the end of therapy patients underwent: an oriented questionnaire evaluating digestive symptoms. 13C-octanoate breath test (13C-OBT) was performed to evaluate GET. Fasting and post-prandial CCK and Motilin serum levels were assessed ELISA. Antiviral therapy was performed according to standard protocols. Results: Baseline none of the patients complained of significant digestive symptoms. GET was normal (t/2 <120 min) in all cases but 3/28 (2%). Baseline and post-prandial CCK and Motilin levels were 0.6±0.4 and 1.57±0.5 and 5.9±5.2 and 1.7±0.9, respectively. At three-month therapy, epigastric burning, belching, epigastric pain, post-prandial fullness, early satiety, bloating, nausea and vomiting were reported by 31%, 57%, 7%, 60%, 57%, 53%, 46% and 14%, respectively. GET rate was significantly delayed in all cases (p <0.0001). CCK fasting and post-prandial serum levels significantly increased (p<0.0001) while Motilin decreased in respect to baseline values (p<0.003). Interestingly, there was a direct significant relation between GI symptom score, GET and CCK and Motilin serum level (p<0.05). After 1 month by the end of therapy, all patients were symptom-free and GET as well as CCK and Motilin serum levels returned to baseline values. Conclusions: Digestive symptoms caused by HCV-antiviral therapy depend on the delay of GET as well as deregulation of CCK/Motilin homeostasis.

OC.07.5 HCV-ANTIVIRAL THERAPY DELAYS GASTRIC EMPTYING TIME AND MODIFIES CCK AND MOTILIN SERUM LEVELS

Background and aim: Digestive symptoms are common side effects of antiviral therapy in patients with HCV chronic hepatitis (CH). The occurrence of digestive symptoms significantly impairs quality of life and requires reduction or even suspension of the therapy in up to 15% of the cases. Recent advances in pathophisiology of functional dyspepsia indicate that delay of gastric emptying time (GET) likely depending on altered Cholecystokinin (CCK) and Motilin serum levels is implicated in the onset of symptoms. In this study we evaluated digestive symptoms, GET and CCK and motilin fasting and post-prandial serum levels in patients with HCV-related CH before, during and after standard antiviral therapy. Material and methods: Twenty-eight patients (M/F 11/17 male, age range 28-70 yrs) with histologically proven HCV-related CH and absence of digestive diseases were enrolled in the study. Baseline, during the therapy (3th month) and after a month by the end of therapy patients underwent: an oriented questionnaire evaluating digestive symptoms. 13C-octanoate breath test (13C-OBT) was performed to evaluate GET. Fasting and post-prandial CCK and Motilin serum levels were assessed ELISA. Antiviral therapy was performed according to standard protocols. Results: Baseline none of the patients complained of significant digestive symptoms. GET was normal (t/2 <120 min) in all cases but 3/28 (2%). Baseline and post-prandial CCK and Motilin levels were 0.6±0.4 and 1.57±0.5 and 5.9±5.2 and 1.7±0.9, respectively. At three-month therapy, epigastric burning, belching, epigastric pain, post-prandial fullness, early satiety, bloating, nausea and vomiting were reported by 31%, 57%, 7%, 60%, 57%, 53%, 46% and 14%, respectively. GET rate was significantly delayed in all cases (p <0.0001). CCK fasting and post-prandial serum levels significantly increased (p<0.0001) while Motilin decreased in respect to baseline values (p<0.003). Interestingly, there was a direct significant relation between GI symptom score, GET and CCK and Motilin serum level (p<0.05). After 1 month by the end of therapy, all patients were symptom-free and GET as well as CCK and Motilin serum levels returned to baseline values. Conclusions: Digestive symptoms caused by HCV-antiviral therapy depend on the delay of GET as well as deregulation of CCK/Motilin homeostasis.

Side effects of antiviral therapy in patients with chronic hepatitis C infection

Chronic hepatitis C currently represents a global health problem, which is expected to be reduced by pegylated-interferon and ribavirin therapy. We examined 88 patients with chronic hepatitis C, divided into three groups according to their comorbidity: the patients without comorbidity were in group I, group III included the patients on dialysis, and group III included the patients with hemophilia. RESULTS A significant difference was found in the percentage of achieved sustained virological response between the patients on dialysis and other patients, p < 0.05. Having analyzed the therapy adverse effects, we observed a significantly higher decrease of erythrocytes count, hemoglobin and hematocrit levels in dialysis patients compared to others (p < 0.01). The patients on hemodialysis predominantly had anemia and leukopenia, while thrombocytopenia was equally present in all groups. The dominant clinical side effect was flu-like syndrome, present in more than a half of patients. The therapy positive effect is usually accompanied with adverse effects. The lowest therapeutic response was recorded in group II, due to the virus genotype 1. A significant decrease in hematological parameters was determined in all patients. The most common clinical adverse effect was flu-like syndrome, later manifestations included: weight loss, alopecia, insomnia and irritability. Side effects like psychosis, thyroid gland dysfunction or psoriasis were not recorded. A significant decrease in the value of all these hematological parameters was found in all groups of patients. Clinical side effects were present in 60% of patients. Side effects did not lead to discontinuation of therapy, but only to modification of drug doses.

A Multidisciplinary Therapeutic Approach for Reducing the Risk of Psychiatric Side Effects in Patients With Chronic Hepatitis C Treated With Pegylated Interferon α and Ribavirin

To evaluate the effectiveness of psychiatric counseling in reducing the rate of development of psychiatric side effects of antiviral therapy with interferon-α and ribavirin among study participants compared with standard clinical monitoring alone. Interferon-α is used to treat chronic hepatitis C. Interferons may induce adverse events that usually, but not always, reverse within a few days after the end of therapy. Two hundred eleven patients with chronic hepatitis C, genotype 1b were treated with peginterferon and ribavirin for 48 weeks in a prospective trial. Two groups were randomly created. Group A was interviewed by a team of gastroenterologists, psychiatrists, and psychologists and treated with psychotherapy once a month. Group B was monitored once a month according to a conventional protocol that did not include psychotherapy. SVR (sustained viral response), severe psychiatric symptom onset, and mood progression were assessed (P calculated using Fisher exact test, Friedman test, Dunn posttest, and Mann-Whitney U-test). At baseline, there was no difference in depressive symptoms or liver histologic score between the 2 groups. The onset rate of severe psychiatric manifestations was 4.7% (Group A) and 16.1% (Group B) between the 24th and 36th weeks (P<0.01). Fifteen participants in Group A and 39 in Group B required antidepressants and benzodiazepines (P<0.05). Patients can develop depressive symptoms during interferon therapy. Multidisciplinary medical treatment with psychiatric counseling provided during the treatment of chronic hepatitis C may contribute to the decrease or prevent the higher rates of depression associated with interferon treatment.

P81 Psychiatric side effects of antiviral therapy with pegylated interferon and ribavirin are associated with poor response in children with chronic hepatitis C

IntroductionChronic hepatitis C (CHC), a mild disease in childhood, can progress to cirrhosis in young adulthood. Successful Peg-IFN+ribavirin therapy prevents progression, but has, among others, neuropsychiatric (NP) side effects (SE)...

Recurrent Hepatitis C After Liver Transplantation

Decompensated cirrhosis from hepatitis C virus (HCV) genotype 1 is the leading indication for liver transplantation in the United States, accounting for nearly 50% of all liver transplants. Recurrent HCV is universal after liver transplantation in patients viremic at the time of transplantation and leads to cirrhosis in up to 30% of patients by five years. Once cirrhosis develops, the risk of hepatic decompensation is 42% per year. This has led to recurrent HCV emerging as an important yet controversial indication for liver retransplantation and a renewed interest in the role of anti-viral therapies. Since the first report of interferon for recurrent HCV treatment in 1996, there have been several reports in the literature of interferon-based therapies for this silent epidemic. However, these studies are limited by a paucity of randomized controlled trials. Despite encouraging results with pegylated interferon and ribavirin in the non-transplant HCV population, these findings have not translated to transplant recipients where viral eradication is frequently unsuccessful ( < 40%). Although stimulating factors are often used to treat the side effects of anti-viral therapy, they are expensive and their use remains controversial. Rejection due to anti-viral therapy, although rare, continues to be a significant concern. Despite successful HCV eradication in a small percentage of patients, progressive cryptogenic fibrosis can still develop leading to hepatic decompensation requiring retransplantation. The lack of effective therapies, severe side effects and reports of hepatic decompensation despite HCV eradication raises the question of whether recurrent HCV genotype 1 should be treated with interferon-based therapies. Clinical trials of newer antiviral medications are urgently required in these patients who are at risk of rapid development of cirrhosis.

Platelet serotonin (5-HT) levels in interferon-treated patients with hepatitis C and its possible association with interferon-induced depression

Interferon-associated depression is a frequent side effect of antiviral therapy for chronic hepatitis C. The aim of the present study was to investigate the correlation between platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations and IFN-induced depression. The study represents a secondary analysis of a previously published trial on the efficacy of SSRI medication in HCV patients on IFN therapy. Ninety-three patients were longitudinally assessed for depression and platelet serotonin. Evaluation time points were: prior to IFN therapy, at weeks 4, 12, and 24 of IFN treatment, and 4 weeks after antiviral treatment. Depression was assessed using the Hospital Anxiety and Depression Scale (HADS). Platelet serotonin concentrations were measured by ELISA. Platelet serotonin concentrations were significantly decreased during interferon therapy (p=0.001) in 74 of the 93 patients (79.6%). Clinically relevant depression occurred in 33.3% of patients - however, IFN-induced depression was not significantly linked to either baseline 5-HT concentrations or kinetics. In the subgroup of patients with IFN-induced depression who received the selective serotonin reuptake inhibitor (SSRI) citalopram (20 mg daily, n=17), serotonin levels declined further during anti-depressant medication, becoming statistically significant within the first 2 weeks (p<0.001) of SSRI treatment. We demonstrate a significant impact of IFN and SSRI intake on platelet serotonin levels, suggesting a biochemical analogy between 5-HT metabolism in blood platelets and the CNS. Platelet 5-HT levels might serve as a surrogate marker for patient adherence to antiviral and anti-depressant medication. For the prediction of IFN-induced depression, however, platelet 5-HT measurements are not suitable.

Decline in Male Sexual Desire, Function, and Satisfaction During and After Antiviral Therapy for Chronic Hepatitis C

The recommended therapy for chronic hepatitis C, pegylated interferon and ribavirin for 24 or 48 weeks, has many known adverse side effects. The aim of this study was to evaluate the impact of antiviral therapy on male sexual health. As part of the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C), 260 men treated with pegylated interferon alfa-2a and ribavirin completed self-administered questionnaires concerning sexual desire, sexual function, including erectile and ejaculatory function, and sexual satisfaction before, during, and after treatment. Before therapy, 37% of men reported at least some degree of impairment in sexual desire and 44% reported dissatisfaction with their sexual life, while 26% reported impairment in erectile and 22% in ejaculatory function. During therapy, significant declines were observed in all components of sexual health compared with pretreatment. At the end of therapy (24 or 48 weeks), an estimated 38%-48% of men reported that overall sexual function was worse than before treatment. African American patients reported less impairment in sexual desire and satisfaction than Caucasian American patients during therapy. By 24 weeks after treatment, sexual desire and satisfaction improved and were comparable to baseline levels. However, among men who received 48 weeks of therapy, the estimated percentage of men reporting posttreatment erectile or ejaculatory problems remained higher than baseline, although persistent erectile impairment was limited to Caucasian American patients. Sexual impairment is common among men with chronic hepatitis C undergoing therapy with pegylated interferon and ribavirin and should be considered as a potential side effect of antiviral therapy.

Thyroid Disorders and Occurrence of Nonorgan-specific Autoantibodies (NOSA) in Patients With Chronic Hepatitis C Before and During Antiviral Induction Therapy With Consensus Interferon (Interferon Alfacon-1)

Thyroid disorders represent a common side effect of antiviral therapy in patients with chronic hepatitis C (CHC). However, there is strong evidence for a higher prevalence of thyroidal antibodies (TA) and nonorgan-specific autoantibodies (NOSA) even before interferon (IFN) administration. Here, we report for the first time on the distribution and occurrence of TA and NOSA before, during, and after treatment with daily highdosed IFN alfacon-1 [consensus IFN (CIFN)]. Thyrotropin (TSH) levels and antibodies to different autoantigens were analyzed in 217 patients with CHC (29.8% females) who were treated with CIFN induction therapy (27 or 18 mg q.d.). Pretreatment abnormal TSH levels (TSH>3.0 mU/L or <0.4 mU/L) were detected in 15.6% and occurred significantly more often in females (24.6%; P=0.018). TA could be detected only in 2.6%, NOSA in up to 29.9% (47.4% females vs. 24.2% males). During CIFN induction therapy, low TSH levels were detected in 14.1% whereas elevated TSH levels occurred later (week 48) in up to 15.5%, again preferentially in females (42%, P=0.005). In 1.4% of all patients, treatment had to be discontinued because of symptomatic hyperthyroidism. TAs were detected in 10.5% (30.5% females) and NOSA up to 58% during CIFN treatment. During CIFN induction therapy, alterations in TSH levels and an increased prevalence of TA and NOSA are quite common, especially in females. Clinically relevant symptoms occur, however, only in a small number (1.4%). Thus, treatment with daily and high-dose CIFN does not appear to increase the incidence of (severe) thyroidal or other autoimmune disorders compared with standard IFN in patients with CHC.

Drug-Specific Effect of Nelfinavir and Stavudine on Primary Culture of Human Preadipocytes

Lipodystrophic syndrome is a major side effect of antiviral therapy leading to profound disturbances in adipose tissue. Human preadipocyte primary culture represents a model to understand mechanisms by which antiretroviral drugs alter adipocyte biology. The aim of this study was to evaluate the effects of various protease and nucleoside reverse transcriptase inhibitors in this model. We tested the effect of drugs on triglyceride accumulation and expression of specific genes by real-time polymerase chain reaction. To determine differential mechanisms by which the efficient drugs operate, we studied mitochondrial effects by evaluating oxygen consumption rates and nuclear lamina alteration by immunocytology. Only stavudine and nelfinavir, both at 10 microM, altered human adipose cell differentiation, as shown by reduced triglyceride accumulation. Our studies revealed that stavudine increased expression of genes such as PGC1 and LPL and affected mitochondrial respiration. Cells treated with nelfinavir had a lower expression of PPARgamma, LPL, and ap2 and presented disorganization of lamin A/C. Our data suggest for the first time in a model of human adipocytes differentiated in vitro that stavudine and nelfinavir interfere with the process of differentiation by 2 distinct mechanisms. This may be particularly relevant in understanding the physiopathologic mechanisms underlying the lipodystrophic syndrome.

The Congenital Cytomegalovirus Infection: Virus-Host Interaction for Defense and Transmission

The congenital CMV infection is the most common intrauterine transmitted viral infection. Since the first description in 1904 a lot of knowledge on epidemiology has been gained. Socio-economic maternal factors play a major role, and seem to be one of the major reasons for the differences of prevalence of congenital CMV infection between Europe and North America. Concerning the interaction of CMV and placental cells, reactions of the host immune system have a dual effect - protection against the virus on the one hand, and supporting of virus production and release of CMV on the other hand. In the last years new strategies for prevention and therapy of congenital CMV infection have been investigated. Passive immunization for prevention of transmission of the virus seems to be promising, but also therapy with ganciclovir of congenital infected newborns showed good results. Taking the side effects of antiviral therapy into consideration, active and passive immunization may ultimately be the best control strategy for this important public health problem.

Relapse to Opioid Use After Treatment of Chronic Hepatitis C With Pegylated Interferon and Ribavirin

Relapse to Opioid Use After Treatment of Chronic Hepatitis C With Pegylated Interferon and Ribavirin

Managing the hematologic side effects of antiviral therapy for chronic hepatitis C: anemia, neutropenia, and thrombocytopenia.

Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common cause of dose reduction or discontinuation. Bone marrow suppression also contributes to the anemia and is the predominant mechanism for interferon-induced neutropenia and thrombocytopenia. Although dose reduction or discontinuation of combination therapy can reverse these abnormalities, they may reduce virologic response. Hematopoietic growth factors may provide a useful alternative for managing these hematologic side effects without reducing the optimal dose of the combination antiviral regimen. Treatment of anemia also may improve patients' health-related quality of life and their adherence to combination antiviral therapy. The impact of growth factors on sustained virologic response and their cost-effectiveness in patients with chronic hepatitis C need further assessment.

Patients' values for health states associated with hepatitis C and physicians' estimates of those values.

Hepatitis C is the leading cause of chronic hepatitis in the United States. Little information is available regarding how persons with hepatitis C view health with their disease. We studied patients' perceptions about the value of hepatitis C health states and evaluated whether physicians understand their patients' perspectives about this disease. A total of 50 consecutive persons with hepatitis C were surveyed when they presented as new patients to a hepatology practice. Subjects provided utility assessments (preference values) for five hepatitis C health states and for treatment side effects. They also stated their threshold for accepting antiviral therapy. Five hepatologists used the same scales to estimate their patients' responses. On average, patients believed that hepatitis C without symptoms was associated with an 11% reduction in preference value from that of life without infection, and the most serious condition (severe symptoms, cirrhosis) was believed to carry a 73% decrement. Patients judged the side effects of antiviral therapy quite unfavorably, and their median stated threshold for accepting treatment was a cure rate of 80%. Physicians' estimates were not significantly associated with patients' preference values for hepatitis C health states, treatment side effects, or with patients' thresholds for accepting treatment. In multivariate analysis, patients' stated thresholds for taking treatment were significantly associated with their decisions regarding therapy (beta = -2.72+/-1.21, p = 0.025). There was little agreement between patients' preference values about hepatitis C and their physicians' estimates of those values. Utility analysis could facilitate shared decision making about hepatitis C.

Patients’ values for health states associated with hepatitis c and physicians’ estimates of those values

OBJECTIVES: Hepatitis C is the leading cause of chronic hepatitis in the United States. Little information is available regarding how persons with hepatitis C view health with their disease. We studied patients’ perceptions about the value of hepatitis C health states and evaluated whether physicians understand their patients’ perspectives about this disease. METHODS: A total of 50 consecutive persons with hepatitis C were surveyed when they presented as new patients to a hepatology practice. Subjects provided utility assessments (preference values) for five hepatitis C health states and for treatment side effects. They also stated their threshold for accepting antiviral therapy. Five hepatologists used the same scales to estimate their patients’ responses. RESULTS: On average, patients believed that hepatitis C without symptoms was associated with an 11% reduction in preference value from that of life without infection, and the most serious condition (severe symptoms, cirrhosis) was believed to carry a 73% decrement. Patients judged the side effects of antiviral therapy quite unfavorably, and their median stated threshold for accepting treatment was a cure rate of 80%. Physicians’ estimates were not significantly associated with patients’ preference values for hepatitis C health states, treatment side effects, or with patients’ thresholds for accepting treatment. In multivariate analysis, patients’ stated thresholds for taking treatment were significantly associated with their decisions regarding therapy (β = −2.72 ± 1.21, p = 0.025). CONCLUSIONS: There was little agreement between patients’ preference values about hepatitis C and their physicians’ estimates of those values. Utility analysis could facilitate shared decision making about hepatitis C.

Physicians' preference values for hepatitis C health states and antiviral therapy: a survey.

BackgroundPhysicians' perspectives regarding hepatitis C shape their approach to patient management. We used utility analysis to evaluate physicians' perceptions of hepatitis C-related health states (HS) and their threshold to recommend treatment.MethodsA written questionnaire was administered to practicing physicians. They were asked to rate hepatitis C health states on a visual analog scale ranging from 0% (death) to 100% (health without hepatitis C). Physicians then judged quality of life associated with the side effects of antiviral therapy for hepatitis C and indicated the sustained virological response rate that they would require to recommend treatment.ResultsOne hundred and thirteen physicians from five states were included. Median utility ratings for hepatitis C health states declined significantly with increasing severity of symptoms: HS1-No Symptoms, No Cirrhosis (88%; 12% reduction from good health), HS2-Mild Symptoms, No Cirrhosis (66%), HS3-Moderate Symptoms, No Cirrhosis (49%), HS4-Mild Symptoms, Cirrhosis (40%), HS5-Severe Symptoms, Cirrhosis (18%) [p < 0.001]. The median rating for life with side effects of antiviral therapy was 47%, suggesting a 53% reduction from good health. That was similar to the utility value for HS3-Moderate Symptoms, No Cirrhosis. The median threshold value for recommending treatment was a sustained response rate of 60%.Conclusions1) Physicians' utility ratings for hepatitis C health states were inversely related to the severity of disease manifestations described. 2) Physicians viewed side effects of therapy unfavorably and indicated that on average, they would require a 60% sustained response rate before recommending treatment, which far exceeds the efficacy of current antiviral therapy for hepatitis C in the majority of patients.