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Several mammarenaviruses cause severe hemorrhagic fever (HF) disease in humans and pose important public health problems in their regions of endemicity. There are no United States (US) Food and Drug Administration (FDA)-approved mammarenavirus vaccines, and current anti-mammarenavirus therapy is limited to an off-label use of ribavirin that has limited efficacy. Mammarenaviruses are enveloped viruses with a bi-segmented negative-strand RNA genome. Each genome segment contains two open reading frames (ORF) separated by a noncoding intergenic region (IGR). The large (L) segment encodes the RNA dependent RNA polymerase, L protein, and the Z matrix protein, whereas the small (S) segment encodes the surface glycoprotein precursor (GPC) and nucleoprotein (NP). In the present study, we document the generation of a recombinant form of the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) expressing a codon deoptimized (CD) GPC and containing the IGR of the S segment in both the S and L segments (rLCMV/ IGR-CD). We show that rLCMV/IGR-CD is fully attenuated in C57BL/6 (B6) mice but able to provide complete protection upon a single administration against a lethal challenge with LCMV. Importantly, rLCMV/IGR-CD exhibited an unbreachable attenuation for its safe implementation as a live-attenuated vaccine (LAV). IMPORTANCE Several mammarenaviruses cause severe disease in humans and pose important public health problems in their regions of endemicity. Currently, no FDAlicensed mammarenavirus vaccines are available, and anti-mammarenaviral therapy is limited to an off-label use of ribavirin whose efficacy is controversial. Here, we describe the generation of recombinant version of the prototypic mammarenavirus lymphocytic choriomeningitis virus (rLCMV) combining the features of a codon deoptimized (CD) GPC and the noncoding intergenic region (IGR) of the S segment in both S and L genome segments, called rLCMV/IGR-CD. We present evidence that rLCMV/IGR-CD has excellent safety and protective efficacy features as live-attenuated vaccine (LAV). Importantly, rLCMV/IGR-CD prevents, in coinfected mice, the generation of LCMV reassortants with increased virulence. Our findings document a welldefined molecular strategy for the generation of mammarenavirus LAV candidates able to trigger long-term protective immunity, upon a single immunization, while exhibiting unique enhanced safety features, including unbreachable attenuation. [ABSTRACT FROM AUTHOR]

Heartland bandavirus (HRTV) is an emerging tick-borne virus that is distributed in the United States and that causes febrile illness with thrombocytopenia and leukocytopenia. It is genetically close to Dabie bandavirus, which is well known as severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV). The mortality rate of human HRTV infection is approximately 10%; however, neither approved anti-HRTV agents nor vaccines exist. An appropriate animal model should be developed to evaluate the efficacy of antiviral agents and vaccines against HRTV. The susceptibility of IFNAR−/− mice with HRTV infection was evaluated using subcutaneous, intraperitoneal, and retro-orbital inoculation routes. IFNAR−/− mice intraperitoneally infected with HRTV showed the most severe clinical signs, and the 50% lethal dose was 3.2 × 106 TCID50. Furthermore, to evaluate the utility of a novel lethal IFNAR−/− mice model, IFNAR−/− mice were orally administered favipiravir, ribavirin, or a solvent for 5 days immediately after a lethal dose of HRTV inoculation. The survival rates of the favipiravir-, ribavirin-, and solvent-administered mice were 100, 33, and 0%, respectively. The changes in bodyweights and HRTV RNA loads in the blood of favipiravir-treated IFNAR−/− mice were the lowest among the three groups, which suggests that favipiravir is a promising drug candidate for the treatment of patients with HRTV infection. [ABSTRACT FROM AUTHOR]

Background: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection.Methods: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S.Results: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%-1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = -160 pg/mL per day at 24 hours, but no further after Day 4.Conclusions: We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection. [ABSTRACT FROM AUTHOR]

• Our HEV replication monitoring system uses Gaussia luciferase. • We validated candidates using cells robustly producing HEV. • We screened and evaluated anti-HEV drugs with an FDA-approved drug library. • Interferon λ1-3 inhibited HEV propagation in our new system. Hepatitis E, which is caused by hepatitis E virus (HEV), is generally a self-limiting, acute, and rarely fatal disease. It is sometimes fulminant and lethal, especially during pregnancy. Indeed, it occasionally takes a chronic course in immunocompromised individuals. To cure hepatitis E patients, the broad-spectrum antivirals (ribavirin and pegylated interferon α) are used. However, this treatment is insufficient and unsafe in some patients due to embryoteratogenic effects, leukopenia, and thrombocytopenia. In this study, we constructed an HEV replication reporter system with Gaussia luciferase for comprehensively screening anti-HEV drug candidates, and developed a cell-culture system using cells robustly producing HEV to validate the efficacy of anti-HEV drug candidates. We screened anti-HEV drug candidates from United States Food and Drug Administration-approved drugs using the established HEV replication reporter system, and investigated the selected candidates and type III interferons (interferon λ1-3) using the cell-culture system. In conclusion, we constructed an HEV replicon system for anti-HEV drug screening and a novel cell-culture system to strictly evaluate the replication-inhibitory activities of the obtained anti-HEV candidates. Our findings suggested that interferon λ1-3 might be effective for treating hepatitis E. [ABSTRACT FROM AUTHOR]

Background: Influenza continues to have a substantial socioeconomic and health impact despite a long established vaccination programme and approved antivirals. Preclinical data suggest that combining antivirals might be more effective than administering oseltamivir alone in the treatment of influenza.Methods: We did a randomised, double-blind, multicentre phase 2 trial of a combination of oseltamivir, amantadine, and ribavirin versus oseltamivir monotherapy with matching placebo for the treatment of influenza in 50 sites, consisting of academic medical centre clinics, emergency rooms, and private physician offices in the USA, Thailand, Mexico, Argentina, and Australia. Participants who were aged at least 18 years with influenza and were at increased risk of complications were randomly assigned (1:1) by an online computer-generated randomisation system to receive either oseltamivir (75 mg), amantadine (100 mg), and ribavirin (600 mg) combination therapy or oseltamivir monotherapy twice daily for 5 days, given orally, and participants were followed up for 28 days. Blinded treatment kits were used to achieve masking of patients and staff. The primary endpoint was the percentage of participants with virus detectable by PCR in nasopharyngeal swab at day 3, and was assessed in participants who were randomised, had influenza infection confirmed by the central laboratory on a baseline nasopharyngeal sample, and had received at least one dose of study drug. Safety assessment was done in all patients in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01227967.Findings: Between March 1, 2011, and April 29, 2016, 633 participants were randomly assigned to receive combination antiviral therapy (n=316) or monotherapy (n=317). Seven participants were excluded from analysis: three were not properly randomised, three withdrew from the study, and one was lost to follow-up. The primary analysis included 394 participants, excluding 47 in the pilot phase, 172 without confirmed influenza, and 13 without an endpoint sample. 80 (40·0%) of 200 participants in the combination group had detectable virus at day 3 compared with 97 (50·0%) of 194 (mean difference 10·0, 95% CI 0·2-19·8, p=0·046) in the monotherapy group. The most common adverse events were gastrointestinal-related disorders, primarily nausea (65 [12%] of 556 reported adverse events in the combination group vs 63 [11%] of 585 reported adverse events in the monotherapy group), diarrhoea (56 [10%] of 556 vs 64 [11%] of 585), and vomiting (39 [7%] of 556 vs 23 [4%] of 585). There was no benefit in multiple clinical secondary endpoints, such as median duration of symptoms (4·5 days in the combination group vs 4·0 days in the monotherapy group; p=0·21). One death occurred in the study in an elderly participant in the monotherapy group who died of cardiovascular failure 13 days after randomisation, judged by the site investigator as not related to study intervention.Interpretation: Although combination treatment showed a significant decrease in viral shedding at day 3 relative to monotherapy, this difference was not associated with improved clinical benefit. More work is needed to understand why there was no clinical benefit when a difference in virological outcome was identified.Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. [ABSTRACT FROM AUTHOR]

Introduction: New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients.Methods: A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER).Results: In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R.Conclusion: In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV. [ABSTRACT FROM AUTHOR]

Background: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.Aim: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.Methods: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.Results: A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.Conclusions: As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported. [ABSTRACT FROM AUTHOR]

End-stage liver disease secondary to hepatitis C virus (HCV) infection is the major indication for orthotopic liver transplantation (OLT) worldwide. The percentage of HCV patients infected with genotype 4 (G4) among recipients of OLT varies depending on geographic location. In the Middle East, including Saudi Arabia, G4 infection is the most common genotype among transplant recipients. Due to the low prevalence of HC V-G4 in Europe and the United States, this genotype has not been adequately studied in prospective trials evaluating treatment outcomes and remains the least studied variant. The aim of this review is to summarize the natural history and treatment outcome of HCV-G4 following liver transplantation, with particular attention to new HCV therapies. This review incorporates all published studies and abstracts including HCV-G4 patients. [ABSTRACT FROM AUTHOR]

Background: Despite changes in the treatment paradigm towards non-interferon-based therapies, interferon-based treatments are still used in some geographical regions for treating patients with hepatitis C virus (HCV) infection. Use of eltrombopag with interferon-based treatment for patients with thrombocytopenia and HCV was assessed in two similarly designed phase 3 trials (Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects With Hepatitis C-Related Liver Disease [ENABLE-1 and ENABLE-2]). These trials also aimed to determine whether response to antiviral therapy (e.g., sustained virologic response [SVR]) is associated with changes in health-related quality of life (HRQoL). This pooled, post-hoc analysis aimed to (1) determine whether or not specific aspects of clinical response to treatment (i.e., achieving SVR) are associated with a significant change in HRQoL, and (2) to determine the magnitude and direction of the association between important changes in HRQoL, clinical response to interferon-based therapy (e.g., SVR) and treatment (eltrombopag or placebo), and patient and disease attributes.Methods: The Short-Form 36 Health Survey version 2 and Chronic Liver Disease Questionnaire-Hepatitis C Virus version were administered at various time points during the studies. Results from both trials were pooled for the analyses. Logistic regression analysis was used to assess the influence of 5 clinical factors (SVR, early virologic response [EVR], genotype [2/3 vs. non-2/3], treatment [eltrombopag or placebo], and cumulative interferon dose), plus other factors including ethnicity, model of end-stage liver disease score, and platelets as predictors of meaningful changes in HRQoL.Results: Between antiviral therapy baseline and the end of the 24-week post-treatment follow-up, declines in HRQoL were smaller in eltrombopag-treated patients than in placebo-treated patients, but the differences were not statistically significant. Mean changes among patients achieving SVR and EVR were small in comparison to thresholds of minimally important changes. Logistic models did not confirm the strength of the 5 clinical factors as predictors of meaningful changes in HRQoL during antiviral therapy, with the exception of the interaction between SVR and EVR (P = 0.0009). Asian ethnicity had a consistent effect on HRQoL, with East Asian patients being more likely to experience deterioration in HRQoL compared with white and/or other non-East Asian patients.Conclusions: While on active antiviral therapy, declines in HRQoL were not statistically different for eltrombopag-treated patients versus placebo-treated patients, suggesting that eltrombopag neither worsened HRQoL nor mitigated the effects of antiviral therapy on HRQoL. [ABSTRACT FROM AUTHOR]

Background: Infection with hepatitis E virus (HEV) in immunocompromised patients can lead to severe liver disease. Treatment options for HEV include peginterferon or ribavirin, routinely also used for the treatment of hepatitis C virus (HCV) infection. We determined the prevalence and clinical consequences of HEV in United States (US) based patients who underwent liver transplantation (LT) for chronic HCV.Methods: Seroprevalence of HEV in 145 US LT recipients with a history of chronic HCV was determined pre-LT, 1, 3 and 5 years post-LT. All last available samples and all samples in IgM positive patients and post-LT IgG seroconverters were tested for HEV RNA.Results: Overall anti-HEV seroprevalence was 42 %. Five patients were HEV IgM positive pre-LT, one patient had IgM seroconversion post-LT and eight patients had IgG seroconversion post-LT. None of the tested samples were positive for HEV RNA. Eight out of nine of the post-LT seroconverters had been treated for HCV recurrence before or at the moment of seroconversion.Conclusions: LT recipients in the US are at risk of acquiring HEV. Post-LT HCV treatment with interferons and/or ribavirin may have protected patients against chronic HEV. With the arrival of new direct antiviral agents for the treatment of HCV and the elimination of peginterferon and ribavirin from HCV treatment regimens, the prevalence of chronic HEV in this population may rise again. [ABSTRACT FROM AUTHOR]

Background: The standard care of treatment of interferon plus ribavirin (plus protease inhibitor for genotype 1) are effective in 50 % to 70 % of patients with CHC. Several new treatments including Harvoni, Olysio + Sovaldi, Viekira Pak, Sofosbuvir-based regimens characterized with potent inhibitors have been approved by the Food and Drug Administration (FDA) providing more options for CHC patients. Trials have shown that the new treatments increased the rate to 80 % to 95 %, though with a substantial increase in cost. In particular, current market pricing of a 12-week course of sofosbuvir is approximately US$84,000. We determine the cost-effectiveness of new treatments in comparison with the standard care of treatments. Methods: A Markov simulation model of CHC disease progression is used to evaluate the cost-effectiveness of different treatment strategies based on genotype. The model calculates the expected lifetime medical costs and quality adjusted life years (QALYs) of hypothetical cohorts of identical patients receiving certain treatments. For genotype 1, we compare: (1) peginterferon + ribavirin + telaprevir for 12 weeks, followed by 12 or 24 weeks treatment of peginterferon + ribavirin dependent on HCV RNA level at week 12; (2) Harvoni treatment, 12 weeks; (3) Olysio + Sovaldi, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (4) Viekira Pak + ribavirin, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (5) sofosbuvir + peginterferon + ribavirin, 12 weeks for patients with or without cirrhosis. For genotypes 2 and 3, treatment strategies include: (1) peginterferon + ribavirin, 24 weeks for treatment-naïve patients; (2) sofosbuvir + ribavirin, 12 weeks for patients with genotype 2, 24 weeks for genotype 3; (3) peginterferon + ribavirin as initial treatment, 24 weeks for patients with genotype 2/3, follow-up treatment with sofosbuvir + ribavirin for 12/16 weeks are performed on non-responders and relapsers. Results: Viekira Pak is cost-effective for genotype 1 patients without cirrhosis, whereas Harvoni is cost-effective for genotype 1 patients with cirrhosis. Sofosbuvir-based treatments for genotype 1 in general are not cost-effective due to its substantial high costs. Two-phase treatments with 12-week and 16-week follow-ups are cost-effective for genotype 3 patients and for genotype 2 patients with cirrhosis. The results were shown to be robust over a broad range of parameter values through sensitivity analysis. Conclusions: For genotype 1, sofosbuvir-based treatments are not cost-effective compared to Viekira Pak and Harvoni, although a 30 % reduction in sofosbuvir price would change this result. Sofosbuvir + ribavirin are cost-effective as second-phase treatments following peginterferon + ribavirin initial treatment for genotypes 2 and 3. However, there is limited data on sofosbuvir-involved treatment, and the results obtained in this study must be interpreted within the model assumptions. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection causes end-stage liver diseases and hepatocellular carcinoma. In the USA, Canada, and Japan, simeprevir - one of the second -generation HCV NS3/4A protease inhibitors - in combination with peginterferon а-2a or 2b plus ribavirin has recently been approved for HCV genotype 1-infected patients and is now used in daily clinical practice. This review summarizes the mechanism of action of simeprevir and the results of clinical trials of simeprevir and peginterferon plus ribavirin for HCV genotype 1 patients. In general, the simeprevir and peginterferon plus ribavirin treatment is highly effective and its adverse events are similar to those of peginterferon plus ribavirin only, the exception being milder, reversible jaundice. In the near future, the development of interferon-free regimens with simeprevir is expected. Careful attention should be paid to new results of clinical trials with simeprevir. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) infection in immunocompetent patients can lead to chronic hepatitis and liver failure. However, the burden of HEV infection in cancer patients is largely unknown. We studied the characteristics of HEV infection in patients at a tertiary care cancer center in the United States. This retrospective study included adult cancer patients with HEV infection diagnosed between September 2011 to September 2021. A total of 405 patients were tested for HEV, and 63 (16%) had detectable HEV IgG. Thirty-three patients (52%) were male, 43 were born in America (68%), 46 (73%) were screened for HEV because of pre-existing liver conditions, and 22 (35%) had hematological malignancies. Only 2 patients had detectable HEV RNA. The first patient had myelodysplastic syndrome and underwent allogeneic stem cell transplantation (HSCT). He developed elevated liver enzymes with HEV RNA 14,000 IU/mL (4.2 log IU/mL) 13 months after HSCT. After reducing immunosuppression, his HEV viremia resolved. The second patient had diffuse large B-cell lymphoma and underwent anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. She had elevated liver enzymes with HEV RNA 4,560,000 IU/mL (6.7 log IU/mL) 12 months after CAR T-cell therapy. She developed chronic HEV infection, and ribavirin treatment failed. Now she is being considered for salvage treatment with peginterferon alfa-2a and ribavirin. This study is the first report of chronic HEV infection in patients who received CAR T-cell therapy. HEV infection in cancer patients appears to be at least as common as in the general population. Cancer patients with hematologic malignancies may be at risk for HEV viremia and chronic infection refractory to antiviral treatment., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

We focus on the treatment of hepatitis C virus genotypes 2 and 3 with coverage of clinical trials on short-duration treatment course, use of weight-based ribavirin, impact of cirrhosis on treatment decisions, and retreatment of patients with previous treatment failure.Current treatment for patients with non–genotype 1 hepatitis C virus infection consists of pegylated interferon plus ribavirin for 24 weeks, which leads to sustained virologic response (SVR) rates of 65%–80%. In the United States, the ribavirin dose for genotypes 2 and 3 is 800 mg/day. However, the use of weight-based ribavirin allows for the potential to shorten the duration of treatment from 24 to 12–14 weeks without reducing SVR rates in individuals who have undetectable viral loads at treatment week 4 and do not have severe liver disease. For patients who are still viremic at week 4, treatment durations even longer than 24 weeks are advised in Europe. In addition, accumulating evidence shows that for patients with unfavorable baseline characteristics, using weight-based ribavirin may increase SVR. In patients who do not achieve SVR with ribavirin 800 mg/day for 24 weeks, retreatment with weight-based ribavirin should be considered. The impact of new molecules in development will be discussed. [ABSTRACT FROM AUTHOR]

The article discusses a research study which suggests the importance of care management to helping deal with complexities of hepatitis C medication adherence. A comparison of the patient outcome between teleprevir combined with peginterferon-ribavirin treatment and peginterferon-ribavirin alone is presented. The study discusses the side effects of triple therapy and its impact on self-management of disease.

Hepatitis C virus infection is a major public health concern. Approximately 4 million people are reported to be infected with the virus in the United States, and the annual death rate due to HCV-associated decompensated liver failure or hepatocellular carcinoma is estimated to be approximately 18,000 within the next decade. Therapeutic success, as measured by a sustained virologic response, is approximately 50 % in G1 patients with pegylated-interferon/ribavirin-based therapies. Independent studies have reported significant variation in response rates depending on the ethnicity or race of the patient, though the underlying reasons are not well understood. Historically, ethnic populations have been underrepresented in most large clinical trials of HCV therapies, even though these populations have disproportionately high rates of HCV infection. Recent clinical trials have investigated genetic variations in key biological pathways that may underlie the mechanisms responsible for the different rates of HCV clearance and treatment outcomes in ethnic populations treated with pegylated-interferon/ribavirin. However, as novel direct-acting antiviral drugs are added to, and eventually replace, existing treatment regimens, the role of the innate immune response in determining treatment outcomes will diminish. Socioeconomic and biological factors can impact rates of HCV infection, disease progression, and treatment outcomes in minority populations. Improved access to health care, novel antiviral treatments, and a better understanding of the host factors that contribute to disparities in treatment outcomes are expected to result in optimized treatment paradigms that directly target the virus, leading to improved outcomes for all patients. [ABSTRACT FROM AUTHOR]

Background Chronic hepatitis C ( HCV) treatment with pegylated-interferon ( PEG- IFN)/ribavirin ( RBV) is often limited by preexisting medical, psychiatric and psychosocial contraindications. However, limited data exist in general patient populations. Aim To evaluate the percentage of HCV-infected patients in the general US population who may have contraindications to PEG- IFN/ RBV. Methods The General Electric ( GE) Centricity dataset was used to screen the US population between 2004 and 2009 for HCV infection and contraindications to PEG- IFN/ RBV. HCV diagnosis and contraindications were identified using ICD-9- CM codes or laboratory values. Only patients with an encounter 180 days prior to HCV diagnosis were included. Demographic differences were calculated using Pearson's chi-squared test. Frequencies and percentages for absolute and relative contraindications to PEG- IFN and/or RBV were determined and proportions and rates/1000 person-months were calculated. Results A total of 15 561 021 patients were screened, and 45 690 (0.3%) were HCV-positive and were evaluated. Those with contraindications were significantly younger, female, White, not currently married and receiving Medicare or Medicaid coverage (all P < 0.0001). 17.3% had at least one contraindication to PEG-IFN/RBV (5.5 events/1000 person-months); bipolar disorder (6.5%), anaemia (Hgb < 10 g/dL; 5.9%), pregnancy (1.9%) and neutropenia (neutrophils <750 cells/mm3; 1.2%) were most frequently cited. Conclusions Approximately, 17% of HCV-infected patients in the general US population had at least one contraindication to PEG- IFN/ RBV. Most contraindications were relative and potentially modifiable. Clinical assessment of contraindications as relative and/or modifiable should be considered and used to determine if patients could benefit from current PEG- IFN-containing triple therapy or future PEG- IFN- or RBV-free regimens. [ABSTRACT FROM AUTHOR]

Purpose: Autoantibodies to cytoplasmic structures called rods and rings (RR) are primarily specific to patients with hepatitis C virus (HCV) infection treated with pegylated interferon-alpha/ribavirin (IFN/R). Our aim is to examine anti-RR antibodies specificity and correlation with the response to IFN/R therapy in two independent cohorts (US and Italy) of HCV patients. Methods: Sera from the US cohort ( n = 47) and the Italian cohort ( n = 46) pre-selected for anti-RR antibodies were analyzed by immunofluorescence and radioimmunoprecipitation. The prevalence and titers of anti-RR were analyzed for correlation with the response to IFN/R therapy. Results: In the US cohort, anti-RR antibodies were more frequently non-responders to IFN/R (71 % vs 29 % responders). Titers in responder patients ( n = 11) were ≤1:3200, whereas titers in non-responder patients ( n = 27) reached 1:819,200 ( p = 0.0016). In the Italian cohort, anti-RR titers ranged from 1:200 to >1:819,200 and only relapsers had the highest anti-RR titers. Radioimmunoprecipitation demonstrated that anti-RR autoantibodies were mainly anti-inosine monophosphate dehydrogenase 2 (IMPDH2) - 96 % in the Italian cohort vs. 53 % in the US cohort. Conclusions: In the two cohorts analyzed, the anti-IMPDH2 response as a component of the anti-RR response is much more prominent in the Italian cohort. The reason for the difference between the US and Italian cohorts is unclear but it possibly illustrates the heterogeneity in response and the overall negative correlation between the production of these autoantibodies and response to IFN/R therapy. Patients with high titer anti-RR antibodies are either relapsers (Italian) or non-responders/relapsers (US). [ABSTRACT FROM AUTHOR]

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Infection with hepatitis C virus is the most common indication for liver transplantation in the United States. Although recurrence of hepatitis C virus infection is universal following transplantation, the natural history of posttransplantation hepatitis C varies. In general, however, posttransplant hepatitis C virus infection progresses relatively quickly, with 10%-20% of patients developing cirrhosis within 5 years. Risk factors for severe recurrent hepatitis C include donor age, female sex, treatment of rejection, preservation injury, and high viral load pretransplant or early posttransplant. Type of allograft, infection with cytomegalovirus, or type of calcineurin inhibitor used may not play a role. Treatment with interferon + ribavirin in recurrent hepatitis C virus shows mixed results. Sustained virologic response has been observed in only 8%-30% of patients, and side effects of these medications are considerable. Protease inhibitors are not yet approved for the posttransplant population, but clinical trials are under way. Mt Sinai J Med 79:190-198, 2012. © 2012 Mount Sinai School of Medicine [ABSTRACT FROM AUTHOR]

More than three million Americans have chronic hepatitis C infection, and the disease remains one of the most common blood-borne infections in the US. Treatment is focused on the chronic form of the disease, because the acute one tends to be self-limiting. In this article, we review the recent literature regarding the most effective therapy against hepatitis C infection, to confirm the current treatment of choice for the disease. We conclude that combination therapy with pegylated interferon and ribavirin remains the initial treatment of choice. New research focusing on adjuvant therapies, such as protease and polymerase inhibitors, has yielded early data that appear to be promising. [ABSTRACT FROM AUTHOR]

The article presents abstracts on several topics related to liver diseases which include the implications of alcohol on the U.S. healthcare industry and socioeconomic status, the risk factors of Hepatitis C Virus (HCV) infection among Asian American patients, and the use of standard therapy integrated with Peginterferon and Ribavirin in treating mixed Cryoglobulinemia in patients who are resistant to HCV treatment.

Abstract: Background: New therapies for Hepatitis C virus (HCV) are under development that will augment pegylated interferon-alpha plus ribavirin to improve patient outcomes. Data documenting the incremental economic and health burden of patients with HCV relative to those who are not infected with HCV will be required to evaluate the comparative effectiveness of these new therapies. Objective: The objective of this study was to estimate the incremental impact of HCV infection on health care costs and risk of adverse health events. Methods: Paid claims data for commercially insured patients in the United States were used to identify 2 matched cohorts of 8861 patients with and without HCV infection. Propensity score matching was used to adjust for patient demographics, diagnostic mix, prior use, and drug profile. Patients with prior cirrhosis, liver cancer, or liver transplantation were excluded. Differences in the first postindex year associated with the diagnosis of an HCV infection were estimated for adverse event risk (logistic regression), costs (ordinary least square regression), and utilization counts (generalized linear models), controlling for patient demographics, prior use, comorbidity profile, and prescription drug profile. Results: The costs of treating patients infected with HCV and a matched sample not infected with HCV were $37,390 and $13,575, respectively. The incremental cost of HCV infection was estimated at +$23,406, primarily because of higher costs for ambulatory care (+$6531), hospital services (+$1827), and prescription drugs (+$6935). The presence of HCV was associated with a significantly higher risk of hospitalization (odds ratio [OR] = 2.5) and number of hospital admissions (+186%); depression (OR = 2.2); cirrhosis (OR = 65.8); hepatic cancer (OR = 28.1), and liver transplantation (OR = 46.1; P < 0.0001 for all estimates). Conclusions: A diagnosis of HCV infection was correlated significantly with increased adverse event risk and increased health care costs. New alternative treatments are needed that are more efficacious and less burdensome for the patient. Limitations of this study are that only 1 year was used to screen for preexisting conditions and events and that paid claims data do not capture indirect HCV infection costs such as time lost from work. [Copyright &y& Elsevier]

Background: Studies of the retreatment with consensus interferon (CIFN) and ribavirin (RBV) of hepatitis C virus (HCV)-infected patients who failed prior pegylated interferon alfa/ribavirin (PEG-IFN/RBV) have found quite variable efficacy and tolerability of this therapy. As such, CIFN/RBV use and efficacy in clinical practice were evaluated within the Department of Veterans Affairs (VA), the largest national, integrated system for HCV care.Aims: The purpose of this study was to determine rates of sustained virologic response (SVR) and patterns of CIFN/RBV use in the VA. Methods included retrospective review of national VA data in HCV-infected patients who had previously failed≥12 weeks of PEG-IFN/RBV and were prescribed CIFN/RBV between October 1, 2003 and September 30, 2006.Results: A total of 597 patients met the study criteria. CIFN was primarily dosed as 15 mcg subcutaneously daily combined with standard doses of RBV. Mean treatment duration was 21 weeks; CIFN was discontinued within 4 weeks in 24%. Hematological growth factors were used in 49%. Post-treatment viral loads were available in 385 patients. SVR to CIFN/RBV was achieved in 11%, and was significantly higher in prior PEG-IFN/RBV relapsers compared with nonresponders (31% vs. 6%, respectively; P<0.0001). A 2-log10 or greater drop in HCV RNA after 24 weeks of PEG-IFN/RBV was a predictor of subsequent SVR to CIFN/RBV.Conclusions: CIFN/RBV was used frequently in clinical practice for retreatment of PEG-IFN/RBV. In this setting, early treatment discontinuation was common. Overall SVR was low, although response was significantly better in prior PEG-IFN/RBV relapsers and those who had a 2-log(10) or greater decline than in nonresponders. [ABSTRACT FROM AUTHOR]

The article discusses the challenges and developments in the management of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection. A case of HCV/HCV coinfection in an African American old man is described. An overview of the epidemiology of HCV infection is provided. The newly approved medications for HCV infection in the U.S. include ribavirin, pegylated interferon alfa and the HCV serine protease inhibitors telaprevir and boceprevir. The link between HIV/HCV coinfection and the accelerated progression of fibrosis, cirrhosis, hepatocellular carcinoma and end-stage liver disease is tackled. Also discussed are the strategies for enhancing or preserving liver function and for targeting HCV replication.

Telaprevir (LY 570310; LY-570310; LY570310;MP 424;MP-424; VX 950; VX-950) is an orally administered peptidomimetic inhibitor of the hepatitis C virus (HCV) protease NS3/4A. It is being developed by Vertex Pharmaceuticals and its licensees for the treatment of HCV infections and has recently been submitted to the US FDA for approval. As the first ever HCV protease inhibitor in phase III development, it is being studied in trials in combination therapy with pegylated interferon alfa-2a and ribavirin in Europe, the US, Australia, Canada, and Puerto Rico in treatment-naive and treatment-experienced patients with HCV genotype 1 infection. Phase III trials of telaprevir as combination therapy are also in progress in Japan. This review discusses the key development milestones and therapeutic trials of this drug to date. [ABSTRACT FROM AUTHOR]

The article presents a research which analyzes the efficacy of boceprevir in combination with peginterferon alfa-2b and ribavirin for the treatment of patients suffering from genotype 1 hepatitis C infection. It is reported that, boceprevir is an NS3 protease inhibitor, and researchers carried out the test by treating the patients with the combination of boceprevir, peginterferon, and ribavirin, for 48 weeks at 67 sites in the U.S. Canada, and Europe. Researchers conclude that, with the addition of boceprevir, it was found that sustained response rate of the patients doubled as compared to treatment with only peginterferon and ribavirin.

Objective: The purpose of this study was to document real-world treatment patterns, medication adherence, and the impact of adherence on disease-specific and all-cause health-care costs among chronic hepatitis C virus (HCV) patients in a US managed care population. Methods: Commercial insurance claims data between January 1, 2002 and December 31, 2006 from the Ingenix Impact (formerly Integrated Health Care Information Services) database were retrospectively analyzed. Chronic HCV patients with one or more prescriptions for an HCV-specific treatment within 6 months before or at any time after their first observed diagnosis of chronic HCV were selected. Prescribing patterns, treatment cost, and duration of treatment were assessed over the entire therapy period. Medication adherence rates and the relationship between adherence and health-care costs were assessed over the 24-week period after treatment initiation. The results were stratified by key clinical characteristics such as genotype, sustained virologic attainment, and disease severity. Results: Results showed that peginterferon and ribavirin combination regimens were the most common treatments for chronic HCV. The patients underwent treatment for approximately 30–32 weeks on average, and treatment costs were over $20,000 per patient. Adherence to medication was suboptimal, especially among patients with severe disease. Adherent patients had higher pharmacy costs but significantly lower total costs when pharmacy was excluded. Conclusions: New and improved treatments that promote better adherence and impose a lower cost burden on patients and payers are needed. [ABSTRACT FROM AUTHOR]

The article presents the case of a 15 year old girl who died after contracting an influenza A infection in February 2007. The background and prevalence of influenza in the U.S. is discussed. The priorities, composition, and distribution of the influenza vaccine are also discussed. Antiviral treatments and their efficacy, including oseltamivir and ribavirin are mentioned. The author comments on the need to expediate the process of new vaccine development. He concludes that the case presented may have been prevented with vaccination strategies and early antiviral therapy.

Chronic hepatitis C affects 170 million people worldwide, including up to 4 million people in the United States. The current standard of care therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) while highly successful in patients with genotype 2 and 3 infection, allows for sustained virologic response in 42–46% of treatment-naïve genotype 1 patients, comprising about 70% of cases of chronic hepatitis C in the USA. While awaiting approval of Specifically Targeted Antiviral Therapy for HCV (STAT-C) agents, which will require the completion of additional clinical trials, it is important to optimize the dose and duration of currently available treatment modalities, namely PEG-IFN and RBV, for treatment of CHC. Results of several recent trials evaluating optimal dosing of RBV and higher than standard dosing of PEG-IFN in treatment-naïve genotype 1 patients, as well as data from retreatment trials with “induction” doses of PEG-IFN or high-dose RBV in prior non-responders to IFN-based therapy will be reviewed here. The possibility of shorter duration of therapy for genotype 2 and 3 patients based on recent publications and presentations will be discussed as well. [ABSTRACT FROM AUTHOR]

The article discusses the development of therapeutic agents for hepatitis C in the U.S. It is said that interferon alpha was first enhanced for chronic hepatitis C in 1991. Combination therapy with either peginterferon Alfa-2a or Alfa-26 plus ribavirin is the approved standard treatment for the disease by the Food and Drug Administration (FDA) as of 2008. Other therapeutic agents being considered include hepatitis C virus (HCV) polymerase inhibitors, caspase inhibitors and nitazoxanide.

More than 4 million (2%) people in the United States have been infected with the hepatitis C virus, of whom 2.7 million are chronically infected. The current treatment for chronic hepatitis C patients is Interferon and ribavirin combination therapy, which is associated with numerous neuropsychiatric side effects. The most common are fatigue, depression, cognitive dysfunction, and anxiety. Early identification and treatment of these symptoms may not only improve the patient's mental health, but also may increase the patient's functional ability and overall quality of life. Psychiatric nurses can play a pivotal role in the successful management of the neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Pegylated interferon and ribavirin have been the standard treatment for chronic hepatitis C (CHC) since 2001. In the USA, hepatitis C is the most common blood-borne infection and the leading cause of cirrhosis requiring liver transplantation. Due to heightened awareness, more patients are being screened and diagnosed with CHC. Interferon-based therapy will continue to be a mainstay of treatment for years to come. A familiarity with the drugs used for the treatment of CHC is beneficial for most healthcare providers. This article will discuss the use of peginterferon alfa-2b and ribavirin, including dosing, length of treatment, mechanism of action, pharmacodynamics, pharmacokinetics, side effects, monitoring and contraindications, and will provide a future perspective on the treatment of CHC. [ABSTRACT FROM AUTHOR]

Hepatitis C is the most common cause of chronic liver disease in the United States. The prevalence of HCV infection is higher in African Americans and Hispanics than among non-Hispanic whites. African Americans not only have a high prevalence of HCV but they also show lower response rates to treatment with pegylated interferon and Ribavirin. Studies have shown that HCV patients often have low levels of knowledge about the disease, including knowledge about modes of transmission and available treatment options. This study was based in two inner-city hospitals in Brooklyn, New York, Kings County Medical Center and The University Hospital of Brooklyn. The goal of this study was to evaluate the change in knowledge of patients with HCV and their willingness to accept treatment after a single session of on-site education which was delivered as part of a clinic visit. Our patients were from minority ethnic groups, with the majority being African Americans. There was a substantially low knowledge among patients with HCV about the etiologic agent being a virus amongst the twenty five patients who completed the study. After the educational intervention there was an increase in knowledge about risk factors for transmitting HCV, such as unprotected sexual intercourse (100% vs. 88% at baseline), tattooing and body piercing (88% vs. 64% at baseline), and sharing personal items like razors. Knowledge of the risk of developing liver cancer in patients with HCV also increased substantially (96% vs. 77% at baseline). There was a marked increase in the expressed willingness to accept treatment (88% vs. 41% baseline). The results of the educational intervention were very encouraging. These results have implication in setting up a structured educational intervention in liver clinics for HCV patients. [ABSTRACT FROM AUTHOR]

Objective: To review the epidemiology, pathophysiology, and therapeutics of chronic hepatitis C virus (HCV) infection, focusing on patient counseling and adverse effects, to serve as a resource for pharmacists in multiple patient care settings. Data sources: Published articles identified through Medline using search terms such as hepatitis C virus, hepacivirus, ribavirin, interferon alfa-2a, or interferon alfa-2b. Therapeutic guidelines retrieved from www.guidelines.gov and the Centers for Disease Control and Prevention (CDC). Additional resources identified from personal bibliographies collected by the author and bibliographies from gathered articles. Study selection: By the author. Data extraction: By the author. Data synthesis: HCV is a blood-borne pathogen affecting an estimated 4 million Americans and 170 million people worldwide. An estimated two-thirds to three-fourths of those infected with HCV have not been diagnosed, and in the next 10 to 20 years, the number of patients diagnosed with HCV is likely to increase. Thus, the health care community, including pharmacists, needs to be educated about the disease, how it is spread, and the details related to treatment of HCV. The standard therapy for HCV is combination therapy with pegylated interferon and ribavirin. This therapy has a varied rate of response that improves with medication adherence. Adherence is often reduced as a result of adverse effects of therapy. In this article, a basic review of HCV is provided, as well as a thorough discussion of strategies to reduce the incidence and severity of adverse effects related to therapy. Conclusion: Pharmacists have an important role in educating other health care practitioners and the community about HCV, providing injection training and medication and adverse effect counseling for patients initiating therapy, and engaging in follow-up and monitoring of patients to encourage therapeutic success by improving medication adherence and patient tolerance of adverse effects. [ABSTRACT FROM AUTHOR]

HCV infections are two-times more prevalent in black Americans than in whites. We previously reported that treatment with peginterferon alfa-2a plus ribavirin produced a sustained virologic response (SVR) rate of 26% in blacks, a lower efficacy compared with the SVR in whites. Here we detail the safety profile of peginterferon alfa-2a plus ribavirin and the relationship between treatment adherence, defined by cumulative drug exposure, and SVR in 78 black patients infected with HCV genotype 1. Sixty-two (79%) patients completed 48 weeks of combination treatment. Peginterferon alfa-2a dose was modified for neutropenia in 36 patients (46%), whereas ribavirin dose was modified due to anemia in 31 patients (40%). The SVR rate was related to medication exposure, based on the percentage of the planned doses of peginterferon and ribavirin that the patients received. The SVR rates were 33, 25 and 0% in patients who received >80, 61–80 and ≤60% of the planned peginterferon, respectively. The SVR rates were 28, 33 and 18% in patients who received >80, 61–80 and ≤60% of the planned ribavirin. The SVR rate was 29% (11 of 38) in patients who received >80% of the total planned doses of both peginterferon and ribavirin and 7% (1 of 14) in patients who received ≤80% of both medicines. The SVR was 30% in patients who received >60% exposure to both, and 0% in patients with ≤60% exposure. In conclusion, peginterferon alfa-2a plus ribavirin demonstrated good safety and tolerability profiles in blacks infected with HCV genotype 1. Adherence to at least >60% of the planned peginterferon alfa-2a and ribavirin doses for 48 weeks was associated with a greater SVR in black patients with HCV genotype 1 infections. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus is one of the leading causes of liver diseases in adults and it is the most common cause of liver transplantation in the USA. Hepatitis C infection in children is less frequent; there is less information about its clinical course. Compared with adults, there are differences in its mode of acquisition, natural history, complications and even available treatments. The aim of this paper is to give an overview of chronic hepatitis C in children. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a major public health concern. Approximately 4 million people in the United States have been infected with the virus, and up to 85% of them will develop chronic infection. Chronic HCV infection has often been associated with progression of hepatic fibrosis and, in some cases, cirrhosis and end-stage liver disease. The standard of care is combination therapy with pegylated interferon (peginterferon) alfa plus ribavirin. More than 50% of patients with HCV treated with combination therapy achieve a sustained viral response, defined as undetectable hepatitis C viral RNA 6 months after the end of therapy. Effective patient education and drug therapy management are critical in enabling patients to adhere to the treatment regimen, which is either 24 or 48 weeks long, depending on the virus strain. The drug regimen is associated with several possible adverse events as well as weekly subcutaneous administration (of peginterferon alfa). Frequent monitoring of patients and, often, adjustments in the dosage of one or both components of the therapy are necessary during the treatment course. Strategies used by clinical pharmacists at an HCV clinic are discussed that can facilitate a successful treatment outcome for patients with HCV treated with combination therapy, while enabling them to maintain a reasonable quality of life. [ABSTRACT FROM AUTHOR]

Nearly three million persons in the United States are viremic with hepatitis C (HCV). Despite a decreasing incidence of HCV in this country, the prevalence of HCV-related chronic liver disease is increasing. Most infections in the United States are acquired by intravenous drug use. The chronicity rate of HCV is high, reaching 85% in some populations, and the risk of progression to advanced liver disease is an high as 20% within twenty years of infection. Host factors like alcohol use accelerate the rate of progression. The enzyme immunoassay is the preferred initial test for diagnosis: the third generation assay has greater than a 99% specificity in immunocompetent patients. Barring contraindications, the standard of care for treatment of chronic HCV has become pegylated interferon and ribavirin. With this therapy, the care rate for treatment-naïve patients is about 55%, but rates are higher in certain groups. Common side effects of therapy include neuropsychiatric symptoms, influenza-like symptoms and hematological abnormalities.

The article focuses on mania during treatment of chronic hepatitis C with pegylated interferon and ribavirin. Infection with the hepatitis C virus is an important public health problem, causing about 170 million cases of chronic hepatitis C world wide and 2.7 million cases in the United States. The most effective pharmacological therapy for chronic hepatitis C is pegylated interferon-alpha combined with ribavirin, which leads to sustained viral remission rates of 54%-80%, depending on hepatitis C virus genotype.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory diseases in infants, young children, and the elderly. Ribavirin, the only currently approved drug for the treatment of RSV infections in the U.S., requires high doses to be effective. Therefore, it has only a limited clinical efficacy in the treatment of RSV infections. It has been shown that a cellular ribonuclease, RNase L, can be recruited by 2′–5′ linked tetra-adenylates (2–5A) attached to an antisense sequence complementary to the RSV genome to specifically cleave RSV genomic RNA. Here we confirm the antiviral activity of the lead 2–5A antisense compound, RBI034, by using several different viral assays. We demonstrate that RBI034 is more efficient than antisense lacking 2–5A or small interfering dsRNA (siRNA) in inhibiting RSV replication. Although the best antiviral activity of RBI034 was observed with co-treatment of RSV infection, it remained effective even when administrated 24 h after the initiation of infection. Interestingly, the activity of RBI034 can be further enhanced by a combination treatment with ribavirin. At suboptimal concentrations, neither ribavirin nor RBI034 was effective in suppressing RSV replication. However, a combination of these two drugs at the same suboptimal concentrations showed a potent inhibitory activity. The potent reduction of RSV replication by combination treatment was also confirmed in primary human airway epithelial cells. Therefore, a combination therapy of the 2–5A antisense compound RBI034 and ribavirin might be a more effective therapeutic approach for treating RSV infections than ribavirin alone. [Copyright &y& Elsevier]

Evaluates the efficacy and adverse drug reactions of ribavirin for the treatment of severe acute respiratory syndrome (SARS) in the U.S. Risk factor for developing SARS; Number of patients received corticosteroids during the course of illness; Decrease of the levels of calcium in the body.

Describes hepatitis C virus (HCV) infection in inmates at federal correctional facilities in Rhode Island. Participation of inmates with chronic HCV infection; Treatment with interferon-alpha with ribavirin; Finding that the incarcerated population can be effectively treated for HCV infection with interferon and ribavirin.

Abstract In the initial treatment of chronic hepatitis C, interferon-alfa (IFN-α) monotherapy for 24–48 weeks induces sustained response rates of only 10–20%. Combination therapy with IFN-α plus ribavirin induces a sustained response in 40–50% of patients, and can be now recommended as the firstline therapy for chronic hepatitis C. Stopping therapy at week 12 because of persistent viraemia is unnecessary with the combination therapy because later clearance of HCV RNA can still occur with a sustained response. Patients with HCV genotype 1 should receive 48 weeks of combination therapy, in contrast to 24 weeks for patients with genotypes 2 or 3. For patients who cannot tolerate the side effects of ribavirin, such as anaemia, IFN-α at 3 MU three times weekly for 48 weeks is preferred as the initial therapy. The long-acting pegylated IFN can be expected to enhance the efficacy of combination therapy in the treatment of chronic hepatitis C and appears to be much more potent as monotherapy. Further studies are needed to improve the current ‘half-full’ status of chronic hepatitis C treatment. [ABSTRACT FROM AUTHOR]

Assesses the efficacy and side effect profiles of interferon (IFN) with or without ribavirin in the treatment of hepatitis C virus (HCV)-infected patients in the United States. Serologic testing; Focus of therapy; Reduction of the biologic and virologic markers of HCV infection; Sustained response rates with IFN monotherapy for chronic HCV. INSET: Formulary considerations.

Summary: Since its recognition in 1964, La Crosse (LAC) virus has been recognized as an important cause of pediatric encephalitis in the United States. The annual incidence of this illness is believed to be between 20 and 30 cases per hundred thousand, though most cases remain undiagnosed. It is typically responsible for a relatively mild disease in humans, though a sub-group of patients suffer from life-threatening illness characterized by permanent neuropsychiatric sequelae. There are currently no approved medications to treat LAC viral infections. However, an anti-RNA viral treatment might prove useful in reducing the length and severity of illness while potentially reducing the risk of permanent sequelae. Evidence exists that the use of ribavirin may form the basis of an effective treatment for LAC viral infections. We propose that oral ribavirin may provide a useful treatment to limit the severity and improve the prognosis of those suffering from LAC viral infections. [Copyright &y& Elsevier]