Antiviral Treatment In Patients Research Articles

Medicinal Value of Turkey Tail Fungus Trametes versicolor (L.:Fr.) Pilat (Aphyllophoromycetideae)

Trametes versicolor, formerly Coriolus versicolor, is a common fan-shaped polypore fungus of dead and dying trees throughout the world, which is an important part of forest ecology as a primary decomposer of hardwood. The fungus is characterized among the white-rot basidiomycetes. T. versicolor produces a laccase used to detoxify xenobiotics such as polychlorinated biphenyls, dyes, and a variety of synthetic polymers and as a pulp biobleach for making paper.Turkey tail is arguably the best-researched medicinal mushroom, with a number of controlled clinical trials demonstrating increased long-term survivability in patients with gastrointestinal cancers, and to a lesser degree other cancers, with oral application of concentrated extracts of the fruit bodies and mycelium, particularly PSK and PSP. These commercially produced extracts are often prescribed along with chemotherapy for treating cancer in Japan and are paid for by national health care.PSK and PSP have demonstrated a wide range of immunological effects in vitro and in vivo, particularly reticuloendothelial system activation, cytokine modulation (IFN-γ production, IL-2 production), enhancement of dendritic cell viability, T-cell maturation, natural killer cell activity, antibody production, and antitumor and anticancer effects. The extracts can inhibit carcinogenesis and tumor cell growth by activating cancer cell apoptosis.Current clinical use in North America, Europe, and Asia of products containing turkey tail extracts and their use as health food supplements has rapidly increased in the last few years, with many types of products becoming available. They are often recommended as supportive treatment for their supposed immunorestorative effects in patients with chronic conditions such as various cancers and viral syndromes such as hepatitis C and for its hepatoprotective effects.Since 1990, a number of controlled clinical trials have been performed in Japan with PSK as a supportive treatment in hospitals and clinics for treating patients with a variety of cancers, particularly colorectal and stomach cancer, but also breast and lung cancers. PSK is given orally, always along with various chemotherapeutic regimes. In several of these multicentric trials (n = 103−462), the 15-year survival rate was increased by 10−15%, and side effects of chemotherapy, such as nausea and anorexia, were reduced when PSK was given along with chemotherapy. Improvements in immune functions such as blood leukocyte and neutrophil counts, serum IgG and IgM, and body-mass index were seen in patients receiving turkey tail extracts with chemotherapy vs. chemotherapy alone. Fundamental questions about the effectiveness of turkey tail extracts for life prolongation and mitigation of side effects from chemo- and radiotherapy in cancer patients, as well as its effectiveness as an immunorestorative and antiviral treatment in patients with chronic viral syndromes, remain to be fully answered. The dose, the solvents used for extraction, the source of starting material, the question of whether fruiting bodies or more easily obtained mycelium cultures should be used, and the duration of treatment have only been partially clarified. Because ubiquitous cell wall components of fungi (including yeasts) and bacteria, (1→3)-β-D-glucans, are thought to be among the most important active constituents, a careful review of the large body of existing literature on the cellular mechanisms of effects on the immune system with oral exposure of these compounds has to be carefully considered.

Triple combination of thymalfasin, peginterferon alfa‐2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24‐week interim results of a pilot study

Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus (HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination.

High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C

The aim of this study was to determine if body mass index (BMI) was an independent predictor of response to antiviral treatment in patients with chronic hepatitis C. A retrospective review was performed of all patients at a single center with chronic hepatitis C treated with antiviral medication from 1989 to 2000. A sustained response was defined as either negative hepatitis C virus (HCV) RNA by polymerase chain reaction and/or normal alanine aminotransferase (ALT) level (only in those treated before availability of HCV RNA testing) 6 months following completion of therapy. All patients were classified into one of 3 groups according to BMI (normal, <25 kg/m 2; overweight, 25-30 kg/m 2; obese, >30 kg/m 2). A total of 253 patients were treated with either interferon (IFN) monotherapy or IFN in combination with ribavirin. Patients were excluded if predetermined clinical characteristics were unavailable. Using logistic regression, and after adjusting for the examined variables (age, sex, history of alcohol consumption >50 g/d, cirrhosis on pretreatment biopsy, and BMI), likelihood ratio tests showed significant differences in response to treatment according to BMI group ( P = .01), genotype ( P < .01), and cirrhosis ( P < .01). Those with genotypes 2 or 3 had an odds ratio (OR) for success of 11.7 compared with those with genotype 1, cirrhotic patients had an OR of 0.15 compared with noncirrhotic patients, and obese patients had an OR of 0.23 compared with normal and overweight patients. Hepatic steatosis was not an independent risk factor for response to antiviral treatment. In conclusion, obesity, only when defined as a BMI greater than 30 kg/m 2, is an independent (of genotype and cirrhosis) negative predictor of response to hepatitis C treatment. (H epatology 2003;38:639-644.)

Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation

AbstractHepatitis C virus (HCV) may be associated with the mixed cryoglobulinemia syndrome and other B-cell lymphoproliferative disorders (LPDs). The t(14;18) translocation may play a pathogenetic role. Limited data are available regarding the effects of antiviral therapy on rearranged B-cell clones. We evaluated the effects of interferon and ribavirin on serum, B-lymphocyte HCV RNA, and t(14; 18) in 30 HCV+, t(14;18)+patients without either mixed cryoglobulinemia syndrome or other LPDs. The t(14;18) translocation was analyzed by bothbcl-2/JHpolymerase chain reaction andbcl-2/JHjunction sequencing in peripheral blood mononuclear cells in all patients. Fifteen untreated patients with comparable characteristics served as controls. Throughout the study, the presence or absence of both t(14;18) and HCV RNA sequences were, in most cases, associated in the same cell samples. At the end of treatment, t(14;18) was no longer detected in 15 patients (50%) with complete or partial virologic response, whereas it was persistently detected in nonresponders (P< .05), as well as in 14 of 15 control patients. In 4 responder patients, t(14;18) and HCV RNA sequences were no longer detected in blood cells after treatment, but were again detected after viral relapse; the same B-cell clones were involved in the pretreatment and posttreatment periods. In conclusion, this study suggests that antiviral therapy may induce regression of t(14;18)–bearing B-cell clones in HCV+patients and that this phenomenon may be related, at least in part, to the antiviral effect of therapy. This in turn suggests that antiviral treatment may help prevent or treat HCV-related LPDs.

Monitoring Response to Antiviral Therapy for Patients with Chronic Hepatitis C Virus Infection by a Core-Antigen Assay

A recently released immunoassay detecting total serum hepatitis C virus (HCV) core antigen was used to prospectively monitor virological responses to antiviral treatment in patients with chronic HCV infection. Sustained responders cleared core protein from serum within the first month of therapy and maintained stably negative values for the entire duration of follow-up after treatment discontinuation. However, patients who relapsed or failed to respond showed transient negative values and could not be accurately discriminated either because of the intrinsic lower sensitivity of the core-antigen assay than those of molecular assays or because of differentially regulated secretion of immunoreactive core protein from infected hepatocytes.

Predictive response factors for antiviral treatment in patients with chronic hepatitis C: Importance of quasispecies

Predictive response factors for antiviral treatment in patients with chronic hepatitis C: Importance of quasispecies

Effectiveness and cost-effectiveness of initial antiviral treatment in patients with chronic hepatitis C. A German health technology assessment and decision analysis commissioned by the German Federal Ministry of Health

Effectiveness and cost-effectiveness of initial antiviral treatment in patients with chronic hepatitis C. A German health technology assessment and decision analysis commissioned by the German Federal Ministry of Health

In vivo immunization following virus suppression: a novel approach for inducing immune control in chronic hepatitis B.

summary. Antiviral treatment of patients with active chronic hepatitis B may lead to significant reduction in morbidity and mortality. However, after stopping nucleoside therapy, relapse rates are high in those without acquired specific immunity. We have treated two chronic hepatitis B patients with in vivo immunization. In vivo immunization aims to optimize conditions for an effective immune response: following rapid and profound virus suppression by interferon-lamivudine combination therapy, lamivudine is withdrawn intermittently for 4 weeks during continued interferon therapy. In both patients with profound virus suppression a rapid rebound in viral replication was observed after lamivudine withdrawal; despite continued interferon. These periods of renewed viral replication were followed by rises in hepatitis activity. After re-introduction of lamivudine HBV DNA became undetectable by PCR followed by normalization of serum ALT. These observations are a stimulus to further explore the concept of in vivo immunization as a novel therapeutic approach for chronic hepatitis B.

Surprisingly small effect of antiviral treatment in patients with hepatitis C.

The effect and applicability of interferon-based antiviral therapies in the general population of persons with hepatitis C virus (HCV) infection are unknown. To determine the applicability and usefulness of anti-viral therapy in a metropolitan clinic population. Retrospective case series of consecutively referred patients. A teaching county hospital in Cleveland, Ohio. 327 patients referred to a liver clinic after a positive result for antibody against HCV on enzyme-linked immunosorbent assay (ELISA). Treatment rates; reasons for nontreatment. 34 patients had no detectable HCV RNA. Of the remaining 293 patients, 72% were not treated for the following reasons: 37% did not adhere to evaluation procedures, 34% had medical or psychiatric contraindications, 13% had ongoing substance or alcohol abuse, 11% preferred no treatment, and 5% had normal liver enzyme levels. Only 83 patients (28%) were treated; 13% had a sustained viral response. Most patients with HCV infection are not candidates for interferon-based therapies; alternative interventions should be sought for these patients.

Antiviral therapies for herpes zoster infections. Are they economically justifiable?

Antiviral treatment of herpes zoster is controversial because of uncertain benefits and relatively high costs. Most studies show that antiviral therapy lessens acute herpes zoster symptoms and postherpetic neuralgia (PHN). Current clinical recommendations support antiviral treatment of severely symptomatic herpes zoster in all adults, and mild herpes zoster in those 50 or 60 years of age or older. However, it is unclear if these recommended strategies are cost effective. Published studies of herpes zoster costs and the effect of antiviral therapy on costs and quality of life have significant variation in study design and results, as well as many shortcomings in the data. Thus, definitive economic recommendations cannot be made based on the present data. Another approach, which we have used, is to develop a 'reference case' analysis using decision-analysis techniques and the available data to estimate the incremental cost effectiveness of antiviral treatment in patients of differing age and herpes zoster severity. In the baseline analysis, parameter values and assumptions were consistently slightly biased against antiviral use. Effectiveness was measured in quality-adjusted life years (QALYs). We assumed that antiviral treatment did not change PHN risk, but decreased PHN duration in patients older than 50 years. PHN risk increased with age and with acute herpes zoster severity as seen in published data. Mild acute herpes zoster was assumed to have a utility value of 0.9 and severe acute herpes zoster a value of 0.7 on a scale where 0 = death and 1 = perfect health. Treating mildly symptomatic acute herpes zoster cost $US89,200/QALY gained in 40-year-olds, $US47,700/QALY in 60-year-olds and $US40,700/QALY in 70-year-olds (1995 values). Results were most sensitive to variation of antiviral costs (baseline $US134), but changes in acute symptom relief, PHN risk, duration, costs and utility, and antiviral effect on PHN duration increased costs/QALY above $US50,000 in 60- and 70-year-olds in extremes of parameter ranges. However, no variation resulted in treatment of mild illness in 40-year-olds to fall below $US50,000/QALY gained. Treatment of severe acute herpes zoster cost $US29,700, $US18,000 and $US16,500/QALY gained in 40-, 60- and 70-year-olds, respectively. Results were sensitive to variation of antiviral costs (> $US225) and acute symptom relief (< 21%) in 40-year-olds. Based on this analysis, antiviral therapy of herpes zoster seems economically justifiable for mildly symptomatic acute herpes zoster in patients aged 50 years and older, and for severely symptomatic acute herpes zoster in all adults.

Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.

Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia. To investigate the efficacy of anti-viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV-associated symptomatic mixed cryoglobulinaemia. 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12-month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12-months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV-RNA and cryoglobulins were performed. In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow-up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or disappearance of the MC-associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%). Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV-associated MC. The presence of cryoglobulins does not affect the response to anti-viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or disappearance of MC-associated clinical manifestations.

Systemic Necrotizing Vasculitis in a Patient Co-infected with Human Immunodeficiency Virus and Hepatitis C

Systemic vasculitis is a rare but devastating problem in patients with human immunodeficiency virus (HIV). The coinfection with hepatitis C virus (HCV) further complicates the clinical management. We report a 46-year-old woman coinfected with HCV and HIV with a CD4 count of 950/mm who presented with a life-threatening vasculitis of the lungs, kidneys, and skin and who initially responded after use of corticosteroids and then 2 monthly pulses of i.v. cyclophosphamide. Her condition deteriorated when she was switched to azathioprine. Ultimately, the patient died of neutropenic sepsis. On the basis of our experience and an analysis of the literature, we suggest that monthly pulsed i.v. cyclophosphamide and steroids might be used as an induction therapy, followed by antiviral treatment for patients with HIV, HCV, and a life-threatening ischemic vasculitis if the CD4 count is >400/mm. For patients in this complex condition who are receiving immunosuppressants close surveillance for signs of secondary infection, and prophylactic trimethoprim/sulfamethoxazole, are advised. The use of interferon alpha, ribavirin, i.v. immunoglobulin, and plasmapheresis are alternatives for patients with milder vasculitis.

Clinical implications of hepatitis C viral kinetics

Antiviral treatment of patients with chronic hepatitis C can perturb the steady-state of virus production and clearance. From serial measurements of changes in viremia, kinetic information on the dynamics of hepatitis C virus (HCV) replication can be obtained. After a delay of about 9 h due to interferon-α pharmacokinetics, the decline of viremia in patients treated with interferon-α is characterized by a concave shape. In the first phase (day 1) a rapid dose-dependent decline in viral load is observed. The second phase viral decline (≥day 2) shows a much slower decline with no or less pronounced differences between the applied interferon-α schedules. While a first phase decline can be observed in almost all patients treated with interferon-α, non-responders typically reveal no further decline of viremia during the second phase. Kinetic analysis showed that combination therapy with interferon-α plus ribavirin has no direct synergistic antiviral effect in the initial 4 weeks of treatment of HCV-infected patients with 6 MU IFNα three times per week. Calculations revealed a minimum virus production and clearance per day in patients with chronic hepatitis C of approximately 10 10–10 12 virions per day and an in vivo half-life of the virus in the order of a few hours. The high turnover rates of HCV explain the rapid generation of viral diversity and the opportunity for viral escape from the host immune surveillance and antiviral therapy. The implications derived from HCV kinetics comprise the consideration of more aggressive initial dosing regimens (especially daily doses), the possibility to optimize therapy individually not only according to pretreatment parameters but also according to the initial decline of viral load and the perception that eradication of the virus will rely on the half-life of infected cells.

An assessment of the possible protective effect of allopurinol in acute stroke.

Allopurinol has been shown to have a protective effect on ischaemic tissue by the indirect prevention of excessive purine loss. This property was tested in the gerbil model of acute stroke. A total of 69 animals were pretreated with an intraperitoneal injection of either allopurinol (50 mg/kg) or sterile water and then subjected to unilateral ligation of the left common carotid artery under general anaesthesia. The clinical effect of the ligation was grouped into three categories of normal, mild to moderate defect (splayed leg, turning behaviour) and severe defect (death, nonresponsiveness and seizures). More normal animals and fewer severely affected animals were present in the allopurinol treated group compared to controls, but only at 2 to 4 hours after carotid ligation (p less than 0.05). Histological examination of brain tissue from the normal category failed to reveal any difference in subclinical ischaemic damage between the two groups. It was concluded that allopurinol may have a protective effect in acute stroke and that this property warrants further elucidation.