Deficiencies in health-related quality-of-life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016.

Quality of life (QoL) is a relevant end point and a topic of growing interest by both scientific community and regulatory authorities. Our aim was to review QoL prevalence as an end point in cancer phase III trials published in major journals and to evaluate QoL reporting deficiencies in terms of under-reporting and delay of publication. All issues published between 2012 and 2016 by 11 major journals were hand-searched for primary publications of phase III trials in adult patients with solid tumors. Information about end points was derived from paper and study protocol, when available. Secondary QoL publications were searched in PubMed. In total, 446 publications were eligible. In 210 (47.1%), QoL was not included among end points. QoL was not an end point in 40.1% of trials in the advanced/metastatic setting, 39.7% of profit trials and 53.6% of non-profit trials. Out of 231 primary publications of trials with QoL as secondary or exploratory end point, QoL results were available in 143 (61.9%). QoL results were absent in 37.6% of publications in the advanced/metastatic setting, in 37.1% of profit trials and 39.3% of non-profit trials. Proportion of trials not including QoL as end point or with missing QoL results was relevant in all tumor types and for all treatment types. Overall, 70 secondary QoL publications were found: for trials without QoL results in the primary publication, probability of secondary publication was 12.5%, 30.9% and 40.3% at 1, 2 and 3 years, respectively. Proportion of trials not reporting QoL results was similar in trials with positive results (36.5%) and with negative results (39.4%), but the probability of secondary publication was higher in positive trials. QoL is not included among end points in a relevant proportion of recently published phase III trials in solid tumors. In addition, QoL results are subject to significant under-reporting and delay in publication.

Role of circulating endothelial progenitor cells in the reparative mechanisms of stable ischemic myocardium.

BACKGROUND: Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood. METHODS: Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment. RESULTS: Mean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD. CONCLUSION: Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls.

TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P < 0.001) were linked to moderate-to-severe steatosis (≥30%) by multiple logistic regression analysis. When TyG was replaced by HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load.

Fibrin acts as biomimetic niche inducing both differentiation and stem cell marker expression of early human endothelial progenitor cells.

OBJECTIVES: Transplantation of endothelial progenitor cells (EPCs) is a promising approach for revascularization of tissue. We have used a natural and biocompatible biopolymer, fibrin, to induce cell population growth, differentiation and functional activity of EPCs. MATERIALS AND METHODS: Peripheral blood mononuclear cells were cultured for 1 week to obtain early EPCs. Fibrin was characterized for stiffness and capability to sustain cell population expansion at different fibrinogen-thrombin ratios. Viability, differentiation and angiogenic properties of EPCs were evaluated and compared to those of EPCs grown on fibronectin. RESULTS: Fibrin had a nanometric fibrous structure forming a porous network. Fibrinogen concentration significantly influenced fibrin stiffness and cell growth: 9 mg/ml fibrinogen and 25 U/ml thrombin was the best ratio for enhanced cell viability. Moreover, cell viability was significantly higher on fibrin compared to being on fibronectin. Even though no significant difference was observed in expression of endothelial markers, culture on fibrin elicited marked induction of stem cell markers OCT 3/4 and NANOG. In vitro angiogenesis assay on Matrigel showed that EPCs grown on fibrin retain angiogenetic capability as EPCs grown on fibronectin, but significantly better release of cytokines involved in cell recruitment was produced by EPC grown on fibrin. CONCLUSION: Fibrin is a suitable matrix for EPC growth, differentiation and angiogenesis capability, suggesting that fibrin gel may be very useful for regenerative medicine.

Role of endothelial progenitor cell mobilization after percutaneous angioplasty procedure.

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived cells, contributing to endothelial cell regeneration of injured vessels as well as neovascularization of ischemic lesions. EPC levels and function are inversely correlated with cardiovascular risk factors, can predict the occurrence of adverse events and atherosclerotic disease progression. Ischemia and inflammation are the primary triggers for EPC mobilization and homing, however, vascular trauma, as it occurs during surgical procedures, has been demonstrated to stimulate EPC mobilization even in absence of tissue ischemia. The effect of angioplasty on EPCs is not well defined, mainly because of the different and sometimes contrasting clinical results, due to low numbers of patients enrolled and to lack of standardization in evaluating EPCs. Aim of this review is to report recent results on the effect of EPC mobilization and homing after angioplasty, attempting to summarize them in a comprehensive model. The effect on EPCs of different kind of stents and the potential use of new stents able to attract EPCs will be also described. Results obtained in patients undergoing angioplasty in different vascular districts (coronary, peripheral and carotid) will be shown, together with the correlation between circulating progenitor cells and restenosis.

Circulating endothelial progenitor cells characterization, function and relationship with cardiovascular risk factors.

Since the first description of putative progenitor endothelial cells mobilized from bone marrow by stimuli like ischemia and cytokines, several studies in animals have confirmed their role in neovascularization of ischemic organs. In ischemic myocardium endothelial progenitor cells can prevent cardiomyocyte apoptosis, reduce remodeling and improve cardiac function. These observations led to the hypothesis of endothelial progenitor cells as possible cell-based therapy in patients by autologous transplantation in ischemic tissue or by improving peripheral circulating numbers with mobilization by cytokines. Early trials, including a randomized one, suggest that the intracoronary autologous bone marrow cell transfer after myocardial infarction exerts at least short term functional benefits. Since endothelial damage and dysfunction play a critical role in atherosclerosis disease, research interest was addressed to evaluate the role of progenitor endothelial cells in vascular endothelial layer maintenance. Opposing to local resident endothelial cells poor proliferation rate, progenitor endothelial cells regenerative capacity, homing and integration into blood vessels have been interpreted as a protective role of these cells in vascular homeostasis. Indeed, the number and function of endothelial progenitor cells relate with the progression of atherosclerosis; the accumulation of cardiovascular risk factors or an increased overall risk are inversely associated with endothelial progenitor cells number and function. Finally, recent studies have shown a role of progenitor cells numbers to predict cardiovascular events, raising endothelial progenitor cells to the podium of novel prognostic biomarker.

Clinical effects of different types of red cell concentrates in patients with thalassemia and sickle cell disease.

The treatment of thalassemia is still essentially based on continuous transfusion supporting using red cell concentrates (RCC) prepared in different ways. For patients with sickle-cell disorders, either urgent or chronic red blood cell transfusion therapy, is widely used in the management of sickle cell disease (SCD) because it reduces HbS level and generally prevents recurrent vaso-occlusive disease (VOD). Recently, the introduction of pre-storage filtration to remove leukocytes and the use of techniques for multicomponent donation have increased the types of blood components available for transfusion purposes. The clinical effects of different types of blood components in thalassaemic and sickle-cell patients have not been extensively studied so far. We evaluated the impact of the various different blood components currently available on transfusion needs, transfusion intervals and adverse reactions in order to determine which is the most advantageous for transfusion-dependent thalassaemic and sickle-cell patients followed in our centre. We believe that the optimal characteristics of the RCC are aged less than 10 days from time of collection; Hb content greater than 56 g per unit; Hct: 55-60%; volume (including additive) 300 mL+/-20%; leucodepleted to less than 200,000 leukocytes per unit; low cytokine content (achievable by pre-storage filtration carried out between two and 24 hours after the collection); lack of microaggregates (achievable by pre-storage filtration or filtration in the laboratory) and protein content less than 0.5 g per unit for patients allergic to plasma proteins (achievable with manual or automated washing). It is still recommended that the blood transfused should be as fresh as possible, compatible with the centre's product availability and the centre's organisation should be continuously adapted to this aim. We always transfuse blood within 10 days of its collection, respecting Rh and Kell system phenotypes. Pre-storage filtration is strongly recommended, both in order to prevent adverse reactions through the marked leucodepletion (less than 200,000 leukocytes per unit) and for a better standardisation of the final product, including the certainty that the product does not contain clots, an assurance that bed-side filtration cannot give. The RCC should be produced using a method causing as little as possible stress to the red cell membrane. The use of RCC with a high content of Hb (less than 56 g per unit) is strongly recommended, because our study clearly shows that this reduces the number of exposures to donors and the number of accesses to hospital, thus improving the patient's quality of life.

An in vitro study on the free radical scavenging capacity of ergothioneine: comparison with reduced glutathione, uric acid and trolox.

BACKGROUND: Treatment of oxidative stress-related pathologies is a possible therapeutical strategy for the future. Natural product with antioxidant properties could trigger this goal. The aim of this in vitro study was to assess the antioxidant activity of the natural product ergothioneine (EGT), a compound of plant origin, which is assimilated and conserved by mammals in erythrocytes, kidney, seminal fluid and liver. METHODS: We measured the antioxidant activity of EGT as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid (KMBA) by hydroxyl radical, peroxyl radicals and peroxynitrite. The results are expressed as total oxyradical scavenging capacity (TOSC) units. Glutathione (GSH), uric acid and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), the water-soluble analog of vitamin E, were used as the reference antioxidants. RESULTS: EGT was the most active scavenger of free radicals as compared to classic antioxidants as GSH, uric acid and trolox. In particular, the highest antioxidant capacity exhibited by EGT vs. peroxyl radicals (5.53 +/- 1.27 units) resulted 25% higher than the value obtained with the reference antioxidant trolox (4.4 +/- 0.6 units, P < 0.01). The scavenging capacity of EGT towards hydroxyl radicals (0.34 +/- 0.09 units) was 60% higher, as compared to uric acid (0.21 +/- 0.04 units, P < 0.001), which represent the reference antioxidant vs. hydroxyl radicals. Finally, EGT showed the highest antioxidant activity also towards peroxynitrite (5.2 +/- 1.0 units), with a scavenging capacity 10% higher than that of uric acid (4.7 +/- 0.9 units, P < 0.05). CONCLUSIONS: This study showed that EGT has potent intrinsic anti-hydroxyl, anti-peroxyl and anti-peroxynitrite radicals antioxidant activity, as compared to classic molecules with antioxidant capacity as GSH, trolox and uric acid. This appears of interest, given the increasing use of non-vitamins cocktails for therapeutical approaches to many oxidative-induced pathologies.

Oral lichen planus, hepatitis C virus, and HIV: no association in a cohort study from an area of high hepatitis C virus endemicity.

OBJECTIVES: We sought to assess the age-specific prevalence of oral lichen planus (OLP) in Mediterranean patients with chronic hepatitis C virus (HCV) and to evaluate the features of OLP in relation to sex, smoking, HCV genotype, HIV-1 coinfection, and antiviral treatments. METHODS: In all, 178 anti-HCV-positive adults (60 women and 118 men; age range 20-66 years) recruited from two cohorts (104 HIV-negative patients and 74 patients with HIV coinfection) underwent oral examination. RESULTS: Overall prevalence of OLP was 2.8% (5 of 178) (male/female ratio 0.2; odds ratio=0.119; 95% confidence interval=0.013-1.106), only among HIV-negative participants, always in the reticular pattern, and in the adult age. HCV genotype, tobacco smoking, and treatment (interferon alfa/ribavirin) were not significantly associated to OLP. CONCLUSIONS: Among HCV-infected patients, we found a low prevalence of OLP. The absence of OLP in HIV-coinfected patients suggests immunosuppression secondary to defective CD4 functions.

Occult HBV infection and suppression of HCV replication in the early phase of combination therapy for chronic hepatitis C.

BACKGROUND: Occult HBV infection in subjects with chronic hepatitis C is related to more severe disease outcome. It has been suggested that it might reduce sensitivity to antiviral treatment. AIMS: To assess in HBsAg negative subjects with chronic hepatitis C any effect of the presence of HBV genomes in the liver on the early kinetics of HCV-RNA under PEG-IFN plus ribavirin. PATIENTS AND METHODS: Twenty-two anti-HCV and HCV-RNA positive subjects, with biopsy-proven chronic hepatitis C (M/F 15/7; 50 +/- 8.6 years, 16 genotype 1b) were given PEG-IFN alpha 2b 1.0 microg qw plus ribavirin (800 to 1,200 mg daily according to body weight) for an intended 52 week period. Early virological response was assessed over the first 4 weeks of therapy by quantifying HCV-RNA. Occult HBV infection was assessed by testing for HBV-DNA in the liver before therapy. RESULTS: HBV genomes were found in the liver of 7 of 22 (31.4%) patients, unrelated to anti-HBc status. Kinetics of HCV-RNA during the first 4 weeks of antiviral treatment was unaffected by occult HBV infection, both in terms of absolute reduction of viral load and of number of cases with a reduction of > or = 2 log10 on treatment. CONCLUSIONS: Occult HBV infection does not affect the early phase of response to combination therapy. Further follow-up of patients into the maintenance phase of antiviral treatment and after stopping it will clarify if and when occult HBV has a role in reducing sustained virological response.

Psoralen and UVA light: an in vitro investigation of multiple immunological mechanisms underlying the immunosuppression induction in allograft rejection.

Photopheresis (ECP) is a novel immunomodulatory therapy effectively used to treat several T-cell-mediated diseases and to reverse allograft rejection after organ transplantation. It consists of infusion of UVA-irradiated autologous leukocytes collected by apheresis and extracorporeally incubated with 8-methoxypsoralen (8-MOP). In this study we explored the potential immunological events for therapeutic efficacy of photopheresis in preventing allograft rejection by evaluating in vitro the combined effects of 8-MOP and UVA (PUVA) on multiple immunological parameters, such as induction of apoptosis, production of soluble mediators, and expression of cell antigens. Peripheral blood mononuclear cells (PBMCs) obtained from healthy subjects were treated with 8-MOP and UVA at the same doses as those clinically used in ECP. We demonstrate that PUVA treatment induced leukocyte hyporesponsiveness and a decrease in expression of co-stimulatory and adhesion molecules as well as of cytokine levels. Additionally, PUVA treatment induced apoptosis in both mononuclear cells (possibly through the Fas/FasL system and/or the CD38 pathway) and purified monocytes. In conclusion, our work focuses attention on the initial phase of immune response and identifies some new targets of therapy (e.g., costimulatory molecules) able to trigger final effects underlying therapeutic efficacy of photopheresis.

Are hepatitis G virus and TT virus involved in cryptogenic chronic liver disease?

BACKGROUND: Hepatitis G virus can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. Little is known about the relation of another newly discovered agent, the TT virus, with chronic liver disease. AIM: To investigate the rate of infection with hepatitis G virus and TT virus in patients with cryptogenic chronic liver disease. PATIENTS: A total of 23 subjects with chronically raised alanine transaminase and a liver biopsy in whom all known causes of liver disease had been excluded, and 40 subjects with hepatitis C virus-related chronic liver disease. METHODS: Evaluation of anti-hepatitis G virus by enzyme immunoassay. Hepatitis G virus-RNA by polymerase chain reaction with primers from the 5' NC and NS5a regions. TT virus-DNA by nested polymerase chain reaction with primers from the ORF1 region. Results. Hepatitis G virus-RNA was detected in 4 out of 23 patients with cryptogenic chronic hepatitis and in 6 out of 40 with hepatitis C virus chronic hepatitis (17.4% vs 15% p=ns). At least one marker of hepatitis G virus infection (hepatitis G virus-RNA and/or anti-hepatitis G virus, mostly mutually exclusive) was present in 6 out of 23 patients with cryptogenic hepatitis and 16 out of 40 with hepatitis C virus liver disease (26. 1% vs 40% p=ns). T virus-DNA was present in serum in 3 subjects, 1 with cryptogenic and 2 with hepatitis C virus-related chronic liver disease. Demographic and clinical features, including stage and grade of liver histology, were comparable between hepatitis G virus-infected and uninfected subjects. Severe liver damage [chronic hepatitis with fibrosis or cirrhosis) were significantly more frequent in subjects with hepatitis C virus liver disease. CONCLUSIONS: In Southern Italy, hepatitis G virus infection is widespread among patients with chronic hepatitis, independently of parenteral risk factors. Its frequency in subjects with cryptogenic liver disease parallels that observed in hepatitis C virus chronic liver disease, thus ruling out an aetiologic role of hepatitis G virus. TT virus infection is uncommon in patients with cryptogenic or hepatitis C virus-related liver disease who do not have a history of parenteral exposure.

Response-adjusted alpha-interferon therapy for chronic hepatitis C in HIV-infected patients.

In patients with chronic hepatitis C and HIV infection, responsiveness to the standard schedule of alpha-interferon (IFN) is unsatisfactory. To quantify the effectiveness of tailoring IFN dosage according to HCV viral load under treatment, we enrolled 41 patients (M/F 32/9) chronically coinfected by HCV and HIV with chronic liver disease. All were former i.v. drug addicts, with a mean age of 32+/-4 years, and had clinical and histological evidence of chronic hepatitis (10% with cirrhosis). The CDC stage was A1 in five, A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty four patients were on triple therapy with protease inhibitors, 11 were on two-drug anti-HIV regimens and three were untreated. IFN (alphan1 interferon) was started at 3 MU tiw and increased at 6 MU tiw at 4 weeks if serum HCV-RNA had not dropped by at least 50%. IFN was stopped at 24 weeks in non-responders. Eleven patients received a dose increase (total IFN dose at 24 weeks 396 MU), while 16 did not increase the initial dose (total IFN dose at 24 weeks 216 MU). Fourteen subjects stopped within the first weeks due to relapse of drug abuse (ten) or subjective intolerance (four). ALT and HCV-RNA levels were markedly decreased at week 4, and this reduction lasted up to 24 weeks. However only one patient had a complete biochemical and virological end-of-treatment response, which was maintained over a 24 weeks post-therapy follow-up. All other patients relapsed to baseline ALT and HCV-RNA values after stopping IFN. HIV viral load was slightly reduced under IFN therapy, while CD4 counts were unaffected. We conclude that raising the dose of IFN dose not eradicate HCV in most HIV-infected patients, even when HIV is well controlled by treatment. HCV viraemia and necroinflammation are temporarily suppressed by IFN, but the relevance of these surrogate endpoints to progression of liver disease and to survival cannot be assessed.

Advances in the study of secondary metabolites occurring in grapes and wines.

In recent years significant advances have been made in the field of secondary metabolites belonging to the polyphenol group and precursors to varietal aromas. Following research on anthocyanins, flavonoids, flavans and phenolic acids of the benzoic and cinnamic type, hydroxystilbenes were thoroughly investigated because of their pharmacological importance. Their presence in the components of grape skins was first noted in 1980. Varietal aromas have mostly been found in their glycoside form. They are known to belong to the class of terpene alcohols, norisoprenoids and benzenoids, though their role in human metabolism is as yet little known.

Viral and host factors in determining response of relapsers with chronic hepatitis C to retreatment with interferon.

In chronic hepatitis C the rate of relapse after an end-of-treatment response to interferon may exceed 50%. The usefulness of retreatment of relapsers with interferon in obtaining a complete sustained response and the role of clinical, virological and immunological features in determining long-term efficacy of retreatment are unclear. We aimed to assess the efficacy of interferon retreatment in obtaining a complete sustained response, to evaluate whether increasing the dose may enhance responsiveness, and to identify possible predictors of sustained response. We enrolled 42 patients with biopsy-proven chronic hepatitis C without cirrhosis who had previously responded to a six-month course of Interferon-alpha2b (total dose: group A, 22 patients, 234 MU; group B, 20 patients, 468 MU) and then relapsed. All, except one, were HCV-RNA negative at the end of first cycle of interferon; most (31/42, 74%) were infected by HCV 1b. Subjects were randomly allocated to receive another cycle of interferon either at the original dose (group A1: 234 MU, 11 patients; group B1 468 MU, 10 patient) or twice the original dose (group A2: 468 MU, 11 patients; group B2: 936 MU, 10 patients). At the end of the second cycle of interferon, 24 subjects (57%) had normal ALT and were HCV-RNA negative, and 16 (39%) had normal ALT, but were HCV-RNA positive. A complete sustained response was obtained in eight patients (19%), at a similar rate in all treatment groups. Complete sustained responders were different from the other patients in terms of age (35.9 +/- 10.4 vs 44.1 +/- 8.8, P = 0.027), rate of infection with non-1b HCV (6/8 vs 5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428 median copies/ml, P = 0.037) and serum levels of 90K/MAC-2 BP (5.76 +/- 3.01 vs 10.25 +/- 5.16 units/ml, P = 0.02), an N-glycoprotein implicated in cellular defense functions. Multivariate logistic analysis validated age and HCV genotype as independent predictors of CSR. Among noncirrhotic relapsers who received a total interferon dose > or = 234 MU in the first cycle, retreatment usually induced end-of-treatment response. A complete sustained response was obtained in only one of every five subjects. Increasing the dose of interferon above that of the first cycle did not enhance the rate of sustained response. In conclusion we might assert that young subjects infected by non-1b HCV and with low levels of HCV-RNA and of 90K/MAC-2 BP are the best candidates for retreatment.

Long-term course of interferon-treated chronic hepatitis C.

BACKGROUND/AIMS: To evaluate whether sustained response to a-interferon improves clinical outcome in patients with chronic hepatitis C. METHODS: A cohort of 410 consecutive patients (65% with chronic hepatitis, 35% with cirrhosis) were treated with a-interferon in two trials (mean follow-up 62.1 months, range 7-109 months). All were serum HCV RNA positive before therapy and received first 10 then 5 million units of a-2b or a-nl interferon three times weekly for 6 to 12 months. Sustained response was defined as normal aminotransferases 12 months after stopping interferon. RESULTS: Sixty-two patients (15.1%: 54 with chronic hepatitis, eight with cirrhosis) were sustained responders. At the end of follow-up, 56 out of 62 sustained responders (90.3%) were serum HCV RNA negative. No biochemical relapse after 12 months was seen in sustained responders, regardless of initial histology, HCV genotype or persistence of HCV RNA. Although three died of non-hepatic causes, no liver-related events were observed among sustained responders. Complications of liver disease occurred in 34 relapsers/non-responders: nine hepatocellular carcinomas, 21 ascites and four portal hypertensive bleedings. Eleven relapsers/nonresponders died: eight of hepatic and three of non-hepatic causes. Event-free survival was significantly longer in sustained responders than in all the remaining patients. In a regression analysis, sustained response to interferon, low age and absence of cirrhosis were independent predictors of event-free survival. CONCLUSIONS: Hepatitis C virus is probably eradicated and progression of liver disease is prevented in most patients who remain HCV RNA negative with normal transaminases for more than 1 year after stopping treatment.