Increased killer B cells in chronic HCV infection may lead to autoimmunity and increased viral load.

Regulatory B (Breg ) cells are characterized by various membrane markers and the secretion of different inhibitory cytokines. A new subset of Breg cells was identified as CD5hi Fas-ligand (FasL)hi . Their main reported role is to suppress anti-viral and anti-tumour immune responses, and, hence they have been dubbed 'killer' B cells. In this study, we aim to assess the role of these cells in chronic hepatitis C virus (HCV) infection, and determine if they contribute to the increased viral load and persistence of HCV and its related autoimmunity. (i) FasL expression on CD5hi B cells is increased significantly in HCV-infected patients compared to healthy individuals [28·06 ± 6·71 mean fluorescence intensity (MFI) ± standard error of the mean (s.e.m.), median = 27·9 versus 10·87 ± 3·97 MFI ± s.e.m., median = 10·3, respectively, P <  0·0001]. (ii) Killer B cells from HCV patients increased autologous CD4+ T cell apoptosis compared to the apoptosis in healthy individuals [39·17% ± 7·18% mean ± standard deviation (s.d.), median = 39·6 versus 25·92 ± 8·65%, mean ± s.d., median = 24·1%, P <  0·0001, respectively]. A similar increase was observed in CD8+ T cell apoptosis (54·67 ± 15·49% mean ± s.d., median = 57·3 versus 21·07% ± 7·4%, mean ± s.d., median = 20%, P = 0·0006, respectively). (iii) By neutralizing FasL with monoclonal anti-FasL antibodies, we have shown that the induction of apoptosis by killer B cells is FasL-dependent. (iv) Increased expression of FasL on CD5hi B cells is correlated positively with an increased viral load and the presence of anti-nuclear antibodies and rheumatoid factor in HCV. This is the first study in which killer B cells have been suggested to play a pathogenic role in HCV. They seem to be involved in HCV's ability to escape efficient immune responses.

Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C-SCAPE study.

People with hepatitis C virus (HCV) infection other than genotype 1 represent a heterogeneous group. The aim of the phase 2 C-SCAPE study was to evaluate elbasvir/grazoprevir (EBR/GZR), with or without ribavirin (RBV), in participants with HCV genotype 2, 4, 5 or 6 infection. This was a part randomised, open-label, parallel-group study (NCT01932762; PN047-03) of treatment-naive, noncirrhotic participants. Participants with HCV genotype 2 infection received GZR 100 mg + RBV ± EBR 50 mg for 12 weeks and those with genotype 4, 5 or 6 infection were randomized to receive EBR/GZR ± RBV for 12 weeks. The primary endpoint was sustained virological response 12 weeks after completion of treatment (SVR12; HCV RNA <25 IU/mL). Among participants with genotype 2 infection, SVR12 was achieved by 80% (24/30) of those receiving EBR/GZR + RBV and 73% (19/26) of those receiving GZR + RBV. SVR rates were high in participants with HCV genotype 4 infection receiving EBR/GZR with and without RBV (100% [10/10] and 90% [9/10]; respectively). In contrast, the addition of RBV to EBR/GZR appeared to increase SVR12 in participants with genotype 5 infection (EBR/GZR, 25%; EBR/GZR + RBV 100% [4/4]). In participants with genotype 6 infection, SVR12 was 75% (3/4) in both those receiving EBR/GZR and those receiving EBR/GZR + RBV. The safety profile was similar across treatment arms, with adverse events tending to occur more frequently among participants receiving RBV. In conclusion, these data support the inclusion of participants with genotype 4 or 6 infection in the EBR/GZR phase 3 studies. EBR/GZR ± RBV was unsatisfactory for participants with genotype 2 or 5 infection.

Real-world effectiveness of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in patients with hepatitis C virus genotype 1 or 4 infection: A meta-analysis.

The direct-acting antiviral regimen of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r)±dasabuvir (DSV)±ribavirin (RBV) demonstrated high rates of sustained viral response at post-treatment week 12 (SVR12) in clinical trials for treatment of hepatitis C virus (HCV) genotypes (GT) 1 and 4. To confirm the effectiveness of this regimen in the real world, we conducted meta-analyses of published literature on 30 April 2016. Freeman-Tukey transformation determined the SVR rate within GTs 1a, 1b and 4, as well as specific SVR rates by cirrhosis or prior treatment experience status. Rates of virologic relapse, hepatic decompensation, drug discontinuation and serious adverse events were also analysed. In total, 20 cohorts across 12 countries were identified, totalling 5158 patients. The overall SVR12 rates were 96.8% (95% CI 95.8-97.7) for GT1 and 98.9% (95% CI 94.2-100) for GT4. For GT1a patients, the SVR rates were 94% and 97% for those with or without cirrhosis, and 94% overall. For GT1b patients, the SVR rates were 98% and 99% for those with or without cirrhosis, and 98% overall. The virologic relapse rate of GT1 patients was 1.3%, across 3524 patients in nine studies that reported this parameter. The rate of hepatic decompensation was less than 1% across five studies, including 3440 patients, 70% of which had cirrhosis. CONCLUSIONS: Real-world SVR12 rates for OBV/PTV/r±DSV±RBV were consistently high across HCV GT1 and four irrespective of cirrhosis status or prior HCV treatment experience, confirming effectiveness within a diverse patient population across multiple cohorts and countries.

Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1 infection.

Grazoprevir (GZR) is a second-generation hepatitis C virus NS3/4A protease inhibitor. The aim of this study was to evaluate GZR plus ribavirin (RBV) in patients with HCV GT1 infection. Noncirrhotic, IL28B CC patients with HCV genotype 1 infection were randomized to GZR 100 mg once daily and RBV for 12 or 24 weeks. Patients in the 12-week arm with detectable HCV RNA at treatment week 4 (TW4) had treatment extended to 24 weeks (response-guided therapy, RGT). The primary endpoint was sustained virologic response (SVR12) at follow-up week 12 (HCV RNA <25 IU/mL) in the per-protocol (PP) population (excluding patients with important protocol deviations). Twenty-six patients were randomized and 22 were included in the PP population. SVR12 was 58.3% (7 of 12) and 90% (9 of 10) in the RGT and 24-week arms, respectively. Seven PP patients had virologic failure, including one patient in the 24-week arm who relapsed after follow-up week 12. All three breakthrough patients had wild-type (WT) virus at baseline and developed breakthrough at TW6 or TW12 with Y56H, A156T and D168A/N mutations. Of the five relapse patients, four had WT at baseline (at relapse three had WT and one had V55A and D168A), and one had S122A/T at baseline and S122T at relapse. There were no serious adverse events (AEs), discontinuations due to AEs or grade 3/4 elevations in total and/or direct bilirubin. Grazoprevir plus RBV was associated with a rapid and sustained suppression of HCV RNA. These results support further evaluation of grazoprevir-based regimens (NCT01716156; protocol P039).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Peginterferon alfa-2b plus weight-based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response.

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR.

Elevated serum B-Lymphocyte activating factor (BAFF) in chronic hepatitis C virus infection: association with autoimmunity.

In this study we aimed to determine whether serum B-lymphocyte activating factor (BAFF) level is increased in patients with chronic hepatitis C virus (HCV) infection, and to assess its association with HCV-related autoimmunity. Sixty-five patients with chronic HCV infection were compared with two disease control groups [57 patients with systemic lupus erythematosus (SLE) and 15 with chronic hepatitis B virus (HBV) infection] and a healthy control group of 35 individuals. A special attention was given to HCV-related arthralgia and or vasculitis. Serum BAFF was assessed in all studied individuals, whereas rheumatoid factor (RF), anti-cardiolipin antibodies (aCL), and cryoglobulins were determined in HCV and HBV infected patients, and anti-dsDNA antibodies and aCL were assessed in patients with SLE. Mean serum BAFF was increased in patients with HCV infection and SLE (2.4+/-0.8 ng/ml and 3.1+/-1.34 ng/ml respectively) compared to 1.1+/-0.14 ng/ml in patients with HBV; and to 1.1+/-0.27 in healthy controls (all, p<0.0001). The elevation in serum BAFF was associated with HCV-related arthralgia and or vasculitis (p<0.0001), and with the presence of aCL and of cryoglobulins. HBV patients lacked features suggestive of autoimmunity. In SLE patients, elevated serum BAFF was in association with the presence of anti-dsDNA (p=0.002). As in other autoimmune diseases, increased serum BAFF was also found in patients with chronic HCV infection. Elevated serum BAFF levels were associated with clinical and laboratory features of autoimmunity, suggesting that BAFF may play a role in HCV-related autoimmunity.

Aortic involvement in rheumatic diseases.

OBJECTIVE: To review the prevalence, mechanisms, presentations and clinical significance of aortic involvement in rheumatic inflammatory diseases. METHODS: The medical literature, available through a PUBMED search was reviewed and the relevant information was summarized. In addition, selected articles related to aortic involvement in rheumatic diseases were included in this review. RESULTS: Rheumatic disorders may be categorized by their propensity to involve the aorta: conditions with a prevalence of 10% and more (Takayasu's arteritis, temporal arteritis, long-standing ankylosing spondylitis, Cogan's syndrome and relapsing polychondritis), disorders with uncommon but well documented aortic involvement and rheumatic conditions with rare case reports of such involvement. Clinical presentation of aortic disease is dependent on the part of aorta involved and may manifest by aortic pain and/or other symptoms caused by aortic dilatation, narrowing or aneurysm. The histopathology of inflammatory aortitis is characterized by lymphoplasmacytic infiltration with or without giant cells or granulomas. On the other hand, non-inflammatory aortic damage in rheumatic diseases may include Marfan-like cystic disintegration of the aortic media as well as accelerated atherosclerosis. Awareness of rheumatic conditions with a high potential for clinically significant aortic involvement may promote referral of such patients for aortic imaging and sometimes surgery before fatal complications intervene. CONCLUSION: Early diagnosis of aortic involvement can be advanced by informed consideration of such a complication in a rheumatic patient.

Lamivudine treatment for acute severe hepatitis B: a pilot study.

BACKGROUND: Experience with lamivudine treatment of immunocompetent patients with acute hepatitis B is limited. AIM OF STUDY: To evaluate the safety and efficacy of lamivudine for the treatment of acute severe hepatitis B virus (HBV) infection in immunocompetent adults. PATIENTS AND METHODS: Fifteen patients (10 men, 5 women, mean age 34.3+/-7.3 years) with severe acute HBV infection were treated with lamivudine 100 mg daily for 3-6 months, starting 3-12 weeks after onset of infection. Prior to treatment, 5 patients had grade 1-4 encephalopathy; all patients had severe coagulopathy (mean INR was 4.5+/-6.4), and all patients had evidence of severe hepatocyte lysis (mean alanine aminotransferase 3738+/-1659 U/L, and mean total serum bilirubin 18+/-6.8 mg/dl). All patients had evidence of highly replicative HBV (mean HBV DNA 13.5 x 10(6)+/-11 x 10(6) copies/ml). RESULTS: Thirteen patients (86.6%) responded to treatment. Encephalopathy disappeared within 3 days of treatment and coagulopathy improved within 1 week. Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and serum liver enzyme levels normalized within 8 weeks. Two patients in whom lamivudine therapy was delayed developed fulminant hepatitis and underwent urgent liver transplantation. (One died of vascular complications 1 month later). The 11 patients who were serum HBeAg-positive before treatment seroconverted, and HBeAb developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested patients, and protective titer of HBsAb developed within 12-16 weeks in 9 of them. Therapy was well tolerated in all cases. CONCLUSIONS: These data indicate that lamivudine induces a prompt clinical, biochemical, serological and virological response in immunocompetent patients with de novo HBV infection. Lamivudine may prevent the progression of severe acute disease to fulminant or chronic hepatitis and should be considered for use in selected patients. A large randomized controlled, double-blind prospective study is needed.

Patterns of cardiovascular reactivity in disease diagnosis.

BACKGROUND: Aberrations of cardiovascular reactivity (CVR), an expression of autonomic function, occur in a number of clinical conditions, but lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome was observed. AIM: To assess whether specific CVR patterns can be described for other clinical conditions. METHODS: Six groups of patients, matched for age and gender, were evaluated with a shortened head-up tilt test: patients with chronic fatigue syndrome (CFS) (n = 20), non-CFS fatigue (F) (n = 15), neurally-mediated syncope (SY) (n = 21), familial Mediterranean fever (FMF) (n = 17), psoriatic arthritis (PSOR) (n = 19) and healthy subjects (H) (n = 20). A 10-min supine phase was followed by recording 600 cardiac cycles on tilt (5-10 min). Beat-to-beat heart rate (HR) and pulse transit time (PTT) were measured. Results were analysed using conventional statistics, recurrence plot analysis and fractal analysis. RESULTS: Multivariate analysis evaluated independent predictors of the CVR in each patient group vs. all other groups. Based on these predictors, equations were determined for a linear discriminant score (DS) for each group. The best sensitivities and specificities of the DS, consistent with disease-related phenotypes of CVR, were noted in the following groups: CFS, 90.0% and 60%; SY, 93.3% and 62.5%; FMF, 90.1% and 75.4%, respectively. DISCUSSION: Pathological disturbances may alter cardiovascular reactivity. Our data support the existence of disease-related CVR phenotypes, with implications for pathogenesis and differential diagnosis.

Evaluation of an indirect enzyme-linked immunosorbent assay for the detection of feline lentivirus-reactive antibodies in wild felids, employing a puma lentivirus-derived synthetic peptide antigen.

An enzyme-linked immunosorbent assay (ELISA) using a puma lentivirus-derived synthetic peptide as coating antigen was evaluated as a diagnostic test for infection with feline immunodeficiency virus (FIV) or related lentiviruses in free-ranging lions. The sensitivity and specificity of the ELISA was determined using two approaches. In the first approach, the results were standardized according to certain statistical criteria, and in the second, the puma lentivirus western blot was used as the gold standard. The sensitivity of the test when compared with the standardized results was 85.4% and the specificity 100%. The sensitivity of the test when using the western blot as the gold standard was 78.6% and the specificity 100%. The test would therefore be well-suited to the screening of populations of wild felids in which FIV or related lentiviruses are endemic. The results also indicate that in spite of genetic divergence between lentiviruses isolated from Panthera and Felis spp., puma lentivirus-derived antigens can be used in immunoassays for the detection of antibodies in Panthera spp. reactive to FIV or related lentiviruses. The results also indicate that the lion population in the Hluhluwe-Umfolozi Game Reserve, South Africa is lentivirus negative.

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome.

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a 'haemodynamic instability score' (HIS). AIM: To assess HIS sensitivity and specificity in the diagnosis of CFS. DESIGN: Prospective controlled study. METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT. RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%. DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician's diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.

Hepatitis C and B-cell lymphoma: the hemato-hepatologist linkage.

Hepatitis C virus (HCV)-lymphotropism may be responsible for the development of mixed cryoglobulinemia (MC) and other lymphoproliferative disorders associated with HCV infection. An association between HCV infection and B-cell lymphoma has been largely demonstrated in several geographical areas with prevalence ranging between 7.4 and 37%. However, the intimate pathogenetic mechanism involved in HCV-associated lymphomas remains considerably unknown. HCV may exerts its oncogenic potential via an indirect mechanism or utilizes other pathways directly. It is reasonable to assume that several different pathogenetic mechanisms operate in the wide spectrum of HCV-related lymphomas which includes the 'idiopathic', non-cryoglobulinemic, intermediate to high-grade lymphoma, and the more common indolent, low-grade lymphoma, preceded by long standing symptomatic MC type II. In most cases, HCV has no significant impact on response to chemotherapy or survival of lymphoma patients. Treatment with chemotherapy is relatively safe, and interruption of treatment regimens is usually not required. Whether to treat low-grade HCV-related lymphomas with anti-viral therapy is still debatable, but encouraging data emerge from recent studies.

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation evolving to an overt lymphoma. Recently, CD81 was identified as an HCV receptor on B-lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. In addition, expansion of CD5+ B lymphocytes was described to be associated with various non-HCV related autoimmune disorders. Therefore, we studied the possible role of peripheral B cells CD81 and CD5 over-expression in the development of HCV-related autoimmunity and their association with disease severity in chronic HCV infection. Peripheral B cells CD5 expression and mean fluorescence intensity (MFI) of CD81 were determined in 30 HCV-infected patients, 30 healthy controls and 15 patients with hepatitis B virus infection using fluorescence-activated cell scan (FACS). We have also investigated the association between peripheral CD5 and CD81 B-cell over-expression and markers of autoimmunity and disease severity in patients chronically infected by HCV. CD5+ B-cells were increased in chronic HCV infection (23.2 +/- 7.2%) compared with those of healthy controls (15 +/- 5.5%) (P < 0.0001) and chronic HBV infection (19 +/- 3.7%) (P = 0.08). CD81 MFI was significantly higher in HCV-infected compared to HBV-infected patients and healthy controls. Both increased CD81 MFI and CD5+ B-cell expansion were associated with the production of rheumatoid factor and mixed cryoglobulins and positively correlated with HCV viral load and histological activity index. The overexpression of CD81 and the expansion of CD5+ peripheral B-cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

Enhanced peripheral T-cell apoptosis in chronic hepatitis C virus infection: association with liver disease severity.

BACKGROUND/AIMS: It has been suggested that enhanced T-cell apoptosis in hepatitis C virus (HCV) infection may lead to down-regulation of their cellular immune response, thus contributing to the persistency of HCV infection. In the present study we have investigated the role of bcl-2 and nuclear factor kappa B (NFkappaB) in dexamethasone-induced apoptosis of peripheral T cells in chronic HCV infection. METHODS: The expression of bcl-2 and NFkappaB in peripheral T cells as well as spontaneous and dexamethasone-induced T-cell apoptosis were studied in HCV-infected patients (n=21), hepatitis B virus (HBV)-infected patients (n=14) and healthy individuals (n=19). These parameters were correlated with markers of autoimmunity and disease severity. RESULTS: NFkappaB, but not bcl-2 expression, was significantly decreased in the HCV-infected patients. This decrease was associated with the presence of mixed cryoglobulins (MC) and rheumatoid factor and was positively correlated with alanine aminotransferase (ALT) levels and histological activity index (HAI). Both spontaneous and dexamethasone-induced T-cell apoptosis were enhanced in HCV-infected patients; however, only the latter was correlated with the presence of MC, ALT levels and HAI. CONCLUSIONS: We confirm previous reports that enhanced T-cell apoptosis in HCV infection may play an important role in disease severity. Decreased expression of NFkappaB is important in the development of peripheral T-cell apoptosis, thus contributing to viral persistence and autoimmunity in these patients.

Management of hepatitis C virus-related arthritis.

Hepatitis C virus (HCV) infection is often associated with extrahepatic manifestations among which arthropathy is common, affecting up to 20% of HCV-infected individuals. This arthropathy is to be distinguished from the more superficially prominent myalgias and fatigue. HCV-related arthritis is commonly presented as rheumatoid-like, symmetrical inflammatory polyarthritis involving mainly small joints, or, less commonly, as mono- or oligoarthritis, usually of the large joints. HCV arthritis usually runs a relatively benign course that, in contrast to 'true' rheumatoid arthritis (RA), is typically non-deforming and is not associated with articular bony erosions. In addition, unlike 'classic' RA, erythrocyte sedimentation rate is elevated only in about half of the patients and subcutaneous nodules are absent. In about two-thirds of the affected individuals morning stiffness may be severe, resolving after more than an hour. Several pathogenetic mechanisms may be involved: HCV arthritis may be part of the syndrome of mixed cryoglobulinaemia, or may be directly or indirectly mediated by HCV. Such possible, but yet not proven, mechanisms include direct invasion of synovial cells by the virus eliciting local inflammatory response, cytokine-induced disease or immune complex disease, particularly in genetically susceptible individuals. The diagnosis of HCV arthritis in patients with positive rheumatoid factor and chronic inflammatory polyarthritis may be difficult. Positive HCV antibody and HCV RNA, and the absence of bony erosions, subcutaneous nodules and antikeratin antibodies, may be useful in distinguishing between HCV-related arthritis and RA. The optimal treatment of HCV-related arthritis has not yet been established. Concerns may be raised regarding the use of immunosuppressive or potentially hepatotoxic drugs. However, it may be suggested that once the diagnosis of HCV-associated arthritis is made, combination antiviral treatment with interferon-alpha and ribavirin should be initiated as part of the therapeutic armamentarium. Low dose oral corticosteroids, nonsteroidal anti-inflammatory drugs, hydroxychloroquine or sulfasalazine in addition to the antiviral therapy can be used to control arthritis-related symptoms. Some patients may need long term anti-inflammatory treatment in various combinations, along with antiviral therapy. In patients with severe, disabling or life-threatening cryoglobulinaemia-related symptoms refractory to antiviral or anti-inflammatory treatment, high dose corticosteroids (including pulse therapy) and/or plasmapheresis may be needed.

The impact of docetaxel, estramustine, and low dose hydrocortisone on the quality of life of men with hormone refractory prostate cancer and their partners: a feasibility study.

OBJECTIVES: The quality of life (QoL) of 44 men with HRPC and 37 partners (primary caregivers, most residing with the patient) was assessed in a multicenter Phase II trial of docetaxel, estramustine and low dose hydrocortisone (CALGB 9780). A secondary objective was to test the feasibility of assessing partners' QoL in a cooperative group setting. PATIENTS AND METHODS: Patients and partners were separately interviewed by telephone at baseline, two, four and six months by a single trained research interviewer. Patients' QoL was measured by the FACT-P, Mental Health Inventory-17 (MHI-17), Brief Pain Inventory (BPI), a two-day log of pain medications, and the OARS for co-morbid conditions. Partners' QoL was measured by the MHI-17, Caregiver Burden Interview, and co-morbid conditions. RESULTS: The QoL study refusal rates were low for patients (4%) and partners (3%). Although patients tended to experience greater treatment side effects in the first two months (FACT Physical Well-Being item, P = 0.057), their cancer-specific emotions (e.g., worrying about worsening health) significantly improved at two and four months (FACT-Emotional Well-Being, P = 0.003, P = 0.03, respectively), as did their prostate cancer-specific physical problems (e.g., urination, pain), at two and four months (FACT-P, P = 0.001, P = 0.005, respectively). Partners' anxiety significantly decreased over time (MHI, P < 0.05). Patients' quality of life at two months was significantly related to their clinical response (FACT-P total and prostate cancer-specific problems, P < 0.05), and their clinical response was significantly related to a decrease in their partners' anxiety at two months (MHI, P < 0.05). CONCLUSIONS: Despite feeling worse from side effects, patients' prostate cancer-specific problems and emotional state significantly improved in the first four months of treatment. With treatment significantly affecting both patients' and partners' lives. and the successful assessment of partners' QoL, QoL of both patients and partners could be used as important endpoints in selected clinical trials.

The effect of antiviral therapy on t(14;18) translocation and immunoglobulin gene rearrangement in patients with chronic hepatitis C virus infection.

The mechanism of lymphomagenesis of hepatitis C virus (HCV)-related B-cell lymphoma is unknown. Recently, it has been suggested that HCV may induce B-cell clonal proliferation and t(14;18) translocation in patients chronically infected with the virus. Thus, this study investigated the effect of antiviral treatment on immunoglobulin heavy-chain gene (IgH) rearrangement and t(14;18) translocation in HCV infected patients. Twenty-nine patients with chronic HCV infection were studied in whom IgH rearrangement and/or t(14;18) translocation were previously detected. The IgH rearrangement (FR3/JH) and t(14;18) translocation (MBR bcl2-JH) were detected in peripheral blood mononuclear cells by polymerase chain reaction. Fifteen of 29 patients (8 with IgH rearrangement, 6 with t(14;18) translocation, and 1 with both) were treated with either interferon-alpha or by combination therapy with interferon and ribavirin for 6 to 12 months. IgH rearrangement became negative in 7 of 9 treated patients compared with only 1 of 8 of nontreated patients (P <.02). The t(14;18) translocation became negative in 6 of 7 treated patients compared with 1 of 6 nontreated patients (P =.03). Disappearance of IgH rearrangement or t(14;18) translocation was strongly associated with virologic response to treatment. Two t(14;18)+ patients developed B-cell lymphoma during follow-up. Antiviral treatment appears to be effective in eliminating the clonal proliferation of B cells in patients with chronic HCV infection and may prevent the subsequent development of lymphoma. The mechanism can be related to a direct effect of interferon-alpha on the proliferating clone or to an indirect effect by eradicating the antigenic stimulus.