A chronic alcoholic man with high fever, neck rigidity and loss of consciousness: remember the Austrian syndrome a commonly unrecognised invasive pneumococcus triad.

Austrian syndrome is a rare medical condition characterised by the triad of pneumonia, meningitis and endocarditis due to Streptococcus pneumoniae Native aortic valve insufficiency is the most common cause of cardiac failure in these patients, requiring valve replacement. We report a 52-year-old chronic alcoholic man who presented with fever, neck rigidity and loss of consciousness. Lumbar puncture revealed central nervous system infection while chest X-ray showed pneumonia. Blood and cerebrospinal fluid cultures revealed S. pneumonia Transoesophageal echocardiography revealed aortic endocarditis with severe valve insufficiency. The patient underwent aortic valve replacement and was finally discharged after completion of 6 weeks intravenous antibiotic treatment. Nowadays, Austrian syndrome is seen infrequently in the antibiotic era. However, clinicians should be aware of this syndrome as its early recognition and prompt combined medical and surgical treatment could reduce morbidity and mortality due to this potentially catastrophic clinical entity.

Current clinical, laboratory, and treatment outcome characteristics of visceral leishmaniasis: results from a seven-year retrospective study in Greece.

OBJECTIVES: Visceral leishmaniasis (VL) is re-emerging in endemic areas. The epidemiological, clinical, laboratory, and treatment outcome characteristics in a large cohort of VL patients is described herein. METHODS: The cases of 67 VL patients (57% male, mean age 56 years) treated in two Greek hospitals over the last 7 years were identified and evaluated retrospectively. RESULTS: Forty-six percent of patients reported contact with animals. Seventeen patients (25%) were immunocompromised, and 22% were co-infected with another pathogen. Sixty-four percent of patients had fever, 57% had weakness, 37% had sweats, 21% had weight loss, and 13% had a dry cough, while 6% developed haemophagocytic syndrome. The median duration of symptoms was 28 days. Fifty-eight percent of patients had splenomegaly, 49% had hepatomegaly, and 36% had lymphadenopathy. The diagnosis was established by positive PCR in peripheral blood (73%) and/or bone marrow specimens (34%). Sixty-one patients (91%) received liposomal amphotericin (L-AMB). Six patients (10%) did not respond or relapsed but were eventually cured after a second cycle of L-AMB. During a 6-month follow-up, the overall mortality was 9%, although none of these deaths was attributed to VL. CONCLUSIONS: VL is still a common disease in endemic areas, affecting immunocompetent and immunocompromised patients. Its diagnosis is challenging, and molecular techniques are valuable and helpful tools to achieve this. Treatment with L-AMB is safe and very effective.

Leishmaniasis revisited: Current aspects on epidemiology, diagnosis and treatment.

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. It is transmitted by phlebotomine female sand flies of the genera Phlebotomus and Lutzomyia in the old and new world, respectively. More than 20 well-recognized Leishmania species are known to infect humans and cause visceral (VL), cutaneous (CL) and mucocutaneous (ML) forms of the disease. Approximately 350 million people are at risk of contracting the disease and an estimated 1.6 million new cases occur annually. The disease mainly affects poor people in Africa, Asia and Latin America, and is associated with malnutrition, population migration, poor residency conditions, frail immune system and lack of resources. Previously, diagnosis of leishmaniasis relied mainly on invasive techniques of detecting parasites in splenic and bone marrow aspirates. Nevertheless, serological tests using the recombinant kinesin antigen (rK39) and molecular methods (polymerase chain reaction) are considered the best options for diagnosis today, despite problems related to varying sensitivities and specificities and field adaptability. Therapy of leishmaniasis ranges from local treatment of cutaneous lesions to systemic often toxic, therapy for disseminated CL, ML and VL. Agents with efficacy against leishmaniasis include amphotericin B, pentavalent antimonial drugs, paromomycin and miltefosine. No single therapy of VL currently offers satisfactory efficacy along with safety. This article provides a brief and updated systematic review on the epidemiology, diagnosis and treatment of this neglected disease.

Asymptomatic bacteriuria in women with autoimmune rheumatic disease: prevalence, risk factors, and clinical significance.

BACKGROUND: Data regarding the prevalence and clinical significance of asymptomatic bacteriuria (AB) in women with autoimmune rheumatic disease (ARD) are scarce. METHODS: In this prospective, case-control study, consecutive female outpatients with ARD were screened for AB. For each patient, demographics, type, duration, and treatment of underlying ARD, and risk factors for urinary tract infection (UTI), were recorded. Age-matched women with endocrine disease, without any autoimmune disease, not receiving immunosuppressive agents were used as controls. Subjects were followed up for 1 year for the development of symptomatic UTI. RESULTS: Two hundred sixty patients with ARD (mean age, 52.4 [standard deviation {SD}, 14.6] years) and 238 controls (mean age, 51.2 [SD, 16.5] years) were enrolled. The majority of patients with ARD (93.5%; 95% confidence interval [CI], 89.7%-95.9%) were receiving immunosuppressive agents. AB was detected in 24 patients with ARD (9.2%; 95% CI, 6.2%-13.4%) and in 22 controls (9.2%; 95% CI, 5.5%-12.9%) (P = 1.000). The most prevalent pathogen was Escherichia coli (16/24 [66%]). Independent predictors for AB among patients were diabetes (odds ratio [OR], 6.6; P = .008) and a longer ARD duration (>84 months; OR, 4.3; P = .018). During the 1-year follow-up, 9 patients with baseline AB remained persistently bacteriuric, whereas 11 were intermittently bacteriuric. Symptomatic UTI developed in 4 of 24 patients (16.7%; 95% CI, 6.1%-36.5%) with baseline AB vs 29 of 236 (12.3%; 95% CI, 8.6%-17.1%) without AB (P = .522). CONCLUSIONS: In our study, the prevalence of AB among women with ARD was not higher than that of controls, and AB was not associated with higher risk for symptomatic UTI. Risk factors for AB were longer duration of ARD and diabetes.

Risk factors for early mortality in haematological malignancy patients with pulmonary mucormycosis.

Pulmonary mucormycosis (PM) is a life-threatening opportunistic mycosis with a variable clinical evolution and few prognostic markers for outcome assessment. Several clinical risk factors for poor outcome present at the diagnosis of PM were analyzed in 75 consecutive hematology patients from 2000-2012. Significant variables (P < 0.1) were entered into a multivariate Cox-proportional hazard regression model adjusting for baseline APACHE II to identify independent risk factors for mortality within 28 days. Twenty-eight of 75 patients died within 4-week follow up. A lymphocyte count < 100/mm³ at the time of diagnosis (adjusted hazard ratio 4.0, 1.7-9.4, P = 0.01) and high level of lactate dehydrogenase (AHR 3.7, 1.3-10.2, P = 0.015) were independent predictors along with APACHE II score for 28-day mortality. A weighted risk score based on these 3 baseline variables accurately identified non-surviving patients at 28 days (area under the receiver-operator curve of 0.87, 0.77-0.93, P < 0.001). A risk score > 22 was associated with 8-fold high rates of mortality (P < 0.0001) within 28 days of diagnosis and median survival of 7 days versus ≥28 days in patients with risk scores ≤22. We found that APACHE II score, severe lymphocytopenia and high LDH levels at the time of PM diagnosis were independent markers for rapid disease progression and death.

Impaired bactericidal but not fungicidal activity of polymorphonuclear neutrophils in patients with chronic lymphocytic leukemia.

We examined the qualitative polymorphonuclear neutrophil (PMN)-associated immune impairment in patients with chronic lymphocytic leukemia (CLL) by characterizing phagocytic killing of key non-opsonized bacterial (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal (Candida albicans and Aspergillus fumigatus) pathogens. Neutrophils were collected from 47 non-neutropenic patients with CLL (PMN count > 1000/mm(3)) and age-matched and young healthy controls (five each). A subset of patients (13%) had prior or subsequent infections. We found that the patients with CLL had diminished PMN microbicidal response against bacteria but not against fungi compared with the controls. Compared to patients with effective PMN responses, we did not identify differences of basal PMN pathogen-associated molecular pattern receptor gene expression, soluble pathogen-associated molecular pattern gene expression or inflammatory cytokine signatures in patients with impaired PMN responses when PMNs were analyzed in multiplex real-time polymerase chain reaction assays. However, differences in PMN microbicidal response against A. fumigatus in patients with CLL were associated with the degree of hypogammaglobulinemia.

Candiduria in haematologic malignancy patients without a urinary catheter: nothing more than a frailty marker?

There is scarcity of data regarding significance of candiduria in patients with haematologic malignancies and its association with invasive candidiasis. To that end, we retrospectively evaluated all hospitalised, non-intensive care unit patients with haematologic malignancies and candiduria during a 10-year period (2001-2011). To decrease the possibility of bladder colonisation and sample contamination, we excluded all patients with candiduria who had urinary catheters and those with concomitant bacteriuria. Twenty-four such patients (21 females) were identified, with median age at diagnosis 62 years (range, 20-82 years). Acute leukaemia was the most common underlying disease (54%); 62% of these cases were not in remission. Twenty-nine percent of the patients had diabetes mellitus and 25% were neutropenic. The most common isolated Candida species was Candida glabrata (37%), followed by C. albicans (29%). Only 8% of them had urinary tract infection symptoms. However, 88% received systemic antifungals. Candidemia and crude mortality rates at 4 weeks were low (4% and 12% respectively). Isolated candiduria in patients with haematologic malignancies has risk factors similar to those in other hospitalised patients, and it does not seem to be a strong predictor of subsequent invasive candidiasis.

The impact of azole resistance on aspergillosis guidelines.

Azole resistance in Aspergillus species may be on the rise, with significant potential implications for the management of invasive aspergillosis. The main mechanism of azole resistance in Aspergillus fumigatus is via alterations of the target enzyme CYP51A. Such azole resistance is either primary or secondary (in the setting of prior azole exposure) and can be derived either from single or multiple mutations. Irrespective of the amino acid substitution type in CYP51A, azole-resistant Aspergillus isolates are always itraconazole resistant. There is significant variability among studies and centers in the prevalence of azole resistance, and this is a multifactorial issue. Nevertheless, the exact frequency of azole resistance is unknown, in part because of the low culturability of the fungus in patients with aspergillosis. This work aims to provide an overview of the current knowledge in Aspergillus azole resistance and raises questions for future research and practical implications in the management of aspergillosis.

Impaired distensibility of ascending aorta in patients with HIV infection.

BACKGROUND: Our aim was to investigate the aortic distensibility (AD) of the ascending aorta and carotid artery intima-media thickness (c-IMT) in HIV-infected patients compared to healthy controls. METHODS: One hundred and five HIV-infected patients (86 males [82%], mean age 41 ± 0.92 years), and 124 age and sex matched HIV-1 uninfected controls (104 males [84%], mean age 39.2 ± 1.03 years) were evaluated by high-resolution ultrasonography to determine AD and c-IMT. For all patients and controls clinical and laboratory factors associated with atherosclerosis were recorded. RESULTS: HIV- infected patients had reduced AD compared to controls: 2.2 ± 0.01 vs. 2.62 ± 0.01 10(-6) cm(2) dyn(-1), respectively (p < 0.001). No difference was found in c-IMT between the two groups. In multiadjusted analysis, HIV infection was independently associated with decreased distensibility (beta -0.45, p < 0.001). Analysis among HIV-infected patients showed that patients exposed to HAART had decreased AD compared to HAART-naïve patients [mean (SD): 2.18(0.02) vs. 2.28(0.03) 10(-6) cm(2) dyn(-1), p = 0.01]. In multiadjusted analysis, increasing age and exposure to HAART were independently associated with decreased AD. CONCLUSION: HIV infection is independently associated with decreased distensibility of the ascending aorta, a marker of subclinical atherosclerosis. Increasing age and duration of exposure to HAART are factors further contributing to decreased AD.

Concurrent lung infections in patients with hematological malignancies and invasive pulmonary aspergillosis: how firm is the Aspergillus diagnosis?

BACKGROUND: Immunocompromised patients with hematological malignancies and/or recipients of hematopoietic stem cell transplants are constantly exposed to several fungal, bacterial, and viral respiratory pathogens. METHODS: We retrospectively evaluated all patients with invasive pulmonary aspergillosis (IPA) and underlying hematological malignancies for the presence of concurrent, microbiologically documented pulmonary infections during a 5-year period (2005-2010). RESULTS: We found 126 such patients that frequently had coinfections (49%) with respiratory pathogens other than Aspergillus species, with a higher rate in patients with probable IPA (53%) than in those with proven IPA (29%; P=0.038). CONCLUSIONS: As the majority of patients with IPA in daily practice have probable IPA, often according to only the combination of positivity for serological biomarkers and radiological findings, our data may raise skepticism about both the certainty of IPA diagnosis and the evaluation of response to antifungals in a subset of these patients.

Invasive Mold Infections in Pediatric Cancer Patients Reflect Heterogeneity in Etiology, Presentation, and Outcome: A 10-Year, Single-Institution, Retrospective Study.

BACKGROUND: There is scarcity of data regarding invasive mold infections (IMIs) in children with cancer. METHODS: We retrospectively identified patients (18 years old or younger) with malignant disease who developed proven or probable IMIs (European Organization for Research on the Treatment of Cancer/Mycoses Study Group criteria) during a 10-year period (1998-2008). We reviewed their risk factors and clinical characteristics and assessed their crude mortality rates and treatment outcomes 12 weeks after IMI diagnosis. RESULTS: Forty-eight patients (30 males) were identified, 30 (63%) of whom had a proven IMI. The most prevalent mold were Aspergillus species (40%), followed by Mucorales (20%) and Fusarium species (11%). Acute leukemia was the most common underlying malignancy (39 patients, [81%]). Twenty-three (59%) of them had refractory leukemia. Neutropenia was present at the day of IMI diagnosis in 67% of the patients. Sixty-two percent of the patients received prior corticosteroids. The dominant site of infection was the lungs (79%), followed by skin (29%) and sinuses (10%). Seventy-one percent of patients had radiological findings suggestive of fungal pneumonia (either nodules or masses). The mainstay of antifungal therapy was a lipid formulation of amphotericin B. Antifungal therapy resulted in 54% response rate (33% complete) at 12 weeks. The crude 12-week mortality rate was 31%. Logistic regression analysis demonstrated that monocytopenia (P = .013), malnutrition (P = .012), and intensive care admission in the month prior to IMI diagnosis (P = .027) were risk factors for death within 12 weeks. CONCLUSIONS: Although Aspergillus spp. was the most common mold in our pediatric cancer population, the epidemiology of the IMIs was diverse. Adults and children share similar risk factors for and epidemiology of IMIs.

Bilateral dilation of the urinary tract due to iliopsoas pyomyositis: a case report.

INTRODUCTION: Pyomyositis is an acute bacterial infection of the skeletal muscles that arises from hematogenous spread and is caused predominantly by Gram-positive cocci. CASE PRESENTATION: We report a case of iliopsoas pyomyositis in a 25-year-old Greek Caucasian woman with a history of intravenous drug use. Her condition was complicated by bilateral dilation of the ureters and renal calyces as a result of mechanical pressure from inflammation and edema of the involved muscle. The patient did not present aggravation of renal function and was treated successfully solely with intravenous antibiotics, without surgical intervention. This is the first case report describing iliopsoas pyomyositis with reversible bilateral dilation of the urinary tract that was treated successfully with intravenous antibiotics, without surgical intervention. CONCLUSION: We present the first described case of iliopsoas pyomyositis with reversible bilateral hydroureteronephrosis that was treated successfully with intravenous antibiotics, without the necessity of surgical intervention. To our knowledge, this is the first report of its kind in the literature regarding an unexpected event in the course of treating a patient with iliopsoas pyomyositis, and it should be of particular interest to different clinical medical specialties such as internal medicine, infectious disease and urology.

The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts.

The halo sign is a CT finding of ground-glass opacity surrounding a pulmonary nodule or mass. The reversed halo sign is a focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation. In severely immunocompromised patients, these signs are highly suggestive of early infection by an angioinvasive fungus. The halo sign and reversed halo sign are most commonly associated with invasive pulmonary aspergillosis and pulmonary mucormycosis, respectively. Many other infections and noninfectious conditions, such as neoplastic and inflammatory processes, may also manifest with pulmonary nodules associated with either sign. Although nonspecific, both signs can be useful for preemptive initiation of antifungal therapy in the appropriate clinical setting. This review aims to evaluate the diagnostic value of the halo sign and reversed halo sign in immunocompromised hosts and describes the wide spectrum of diseases associated with them.

Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece.

AIM: To assess the hepatitis B virus (HBV)-DNA and the prevalence of occult HBV infection in end-stage renal failure (ESRF) patients from Central Greece. METHODS: Sera from 366 ESRF patients attending five out of six dialysis units from Central Greece were investigated for HBV-DNA by real-time polymerase chain reaction. Only serum samples with repeatedly detectable HBV-DNA were considered positive. IgG antibodies to hepatitis C virus (anti-HCV) were tested by a third generation enzyme linked immunosorbent assay (ELISA), while IgG antibodies to hepatitis E virus (anti-HEV) were tested by two commercially available ELISAs. RESULTS: HBV-DNA was detected in 15/366 patients (4.1%) and HBsAg in 20/366 (5.5%). The prevalence of occult HBV infection was 0.9% (3/346 HBsAg-negative patients). Occult HBV was not associated with a specific marker of HBV infection or anti-HCV or anti-HEV reactivity. There was no significant difference in HBV-DNA titres, demographic and biochemical features, between patients with occult HBV infection and those with HBsAg-positive chronic HBV infection. CONCLUSION: In central Greece, 4% of ESRF patients had detectable HBV-DNA, though in this setting, the prevalence of occult HBV seems to be very low (0.9%).

Occult hepatitis B virus infection in patients with autoimmune liver diseases.

BACKGROUND: Occult hepatitis B virus (HBV) infection is characterized by undetectable serum HBV surface antigen (HBsAg) but detectable HBV-DNA in serum or liver. AIMS: To determine the prevalence and clinical impact of occult HBV in autoimmune liver diseases as similar data are missing. METHODS: One hundred and ninety-six sera samples from HBsAg-negative patients, including 66 autoimmune hepatitis (AIH), 93 primary biliary cirrhosis (PBC) and 37 primary sclerosing cholangitis (PSC), were investigated for HBV-DNA using the polymerase chain reaction (PCR) before treatment initiation. One hundred and three serial samples from 38 AIH patients under immunosuppression and 282 selected blood donors (HBsAg negative; antibodies to HBV-core antigen positive) were also investigated. Fourteen available paraffin-embedded AIH liver samples were also investigated for HBV-DNA by nested-PCR. RESULTS: Hepatitis B virus DNA was detected in the serum of 24/196 patients (12.2%) and 0/282 donors (P=0.0000). Nine patients had AIH (13.6%), eight had PBC (8.6%) and seven had PSC (18.9%) (P=0.0000 vs healthy). HBV-DNA detection in AIH livers was higher than in serum. HBV-DNA was associated neither with HBV markers nor with epidemiological, laboratory and clinical data. Serial testing of AIH patients revealed two HBV-DNA-negative patients before treatment becoming positive during treatment, while all HBV-DNA-positive patients before immunosuppression became negative. CONCLUSION: Based mainly on serum HBV-DNA, we found a significant proportion of autoimmune liver disease patients with occult HBV compared with donors. However, taking into account our results in a small number of liver tissues, it should be emphasized that occult HBV could be even higher when both serum and liver specimens are investigated. Occult HBV does not seem to affect the clinical and laboratory features of the diseases, while AIH patients with occult HBV under immunosuppression do not deteriorate during follow-up.

Lack of association between appendectomy and primary biliary cirrhosis.

OBJECTIVE: In view of the possible implication of various environmental factors in the pathogenesis of primary biliary cirrhosis (PBC), the role of appendectomy in patients with PBC and other chronic liver diseases from Central Greece was investigated. MATERIAL AND METHODS: The medical files of 68 patients with PBC and gender- and age-matched controls with chronic hepatitis C virus (HCV) infection (n=65) and chronic hepatitis B virus (HBV) infection (n=67) were reviewed for the history and time of appendectomy. RESULTS: Nineteen of 68 (27.9%) PBC patients, 32 of 65 (49.2%) patients with chronic HCV infection and 22 of 67 (32.8%) patients with chronic HBV infection had a history of appendectomy. There was a significant higher frequency of appendectomy in patients with chronic hepatitis C (p = 0.012, chi(2) test) compared to patients with PBC. There were no significant differences in the clinical and histological characteristics of PBC patients with or without a history of appendectomy. CONCLUSION: In this case-control study we were unable to provide evidence of an association between primary biliary cirrhosis and the occurrence of appendectomy.

Reversion of severe hepatopulmonary syndrome in a non cirrhotic patient after corticosteroid treatment for granulomatous hepatitis: a case report and review of the literature.

Hepatopulmonary syndrome (HPS) is defined as a clinical triad including liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations. We report a 61-year-old male presented with fatigue, long-lasting fever, loss of weight, signs of portal hypertension, hepatosplenomegaly, cholestasis and progressive dyspnoea over the last year. Clinical, laboratory and histological findings confirmed the diagnosis of granulomatous hepatitis. HPS due to hepatic granuloma-induced portal hypertension was proved to be the cause of severe hypoxemia of the patient as confirmed by contrast-enhanced echocardiography. Reversion of HPS after corticosteroid therapy was confirmed by a new contrast-enhanced echocardiography along with the normalization of cholestatic enzymes and improvement of the patient's conditions. This is the first case of complete reversion of HPS in a non-cirrhotic patient with hepatic granuloma, indicating that intrapulmonary shunt in liver diseases is a functional phenomenon and HPS can be developed even in miscellaneous liver involvement as in this case.

Intrafamilial spread of hepatitis B virus infection in Greece.

OBJECTIVE: No study has investigated the intrafamilial spread of hepatitis B virus (HBV) in Greece. We conducted a 9-year prospective study to determine the rate of HBV spread in family members when a member is identified as an HBV carrier, the possible routes and risk factors for transmission of HBV and the family members with the highest risk of infection according to kinship degrees. METHODS: A total of 387 family members of 166 hepatitis B surface antigen (HBsAg) carriers were investigated for the detection of HBV infection markers using standard enzyme immunoassays; 6.696 blood donors from the same area were used as controls. RESULTS: Serological markers of past or current HBV infection were detected significantly more frequently among family members of HBsAg carriers (23.2 and 15.8%, respectively) compared with blood donors (14.1 and 0.85%, respectively). The prevalence of the above markers was higher among siblings, husbands and parents of the carriers. Offspring of the female index cases had higher rates of current or past infection. HBV infection markers were significantly increased in family members who reported common use of syringes (P<0.001), birth in rural areas (P<0.001) and a low level of education (P<0.001). CONCLUSIONS: We demonstrated a high risk of HBV transmission among family members of HBsAg carriers, which was associated with special risk factors for contracting HBV. Our findings indicate the need for strict adherence to the universal guidelines of vaccination against HBV and also the need for an immediate investigation of other potentially infected relatives among family members of HBsAg carriers.

Leptospirosis and pancytopenia: two case reports and review of the literature.

Besides the classical manifestations, leptospirosis may rarely occur with erythroid hypoplasia and/or pancytopenia. In this study, we reported two cases of leptospirosis presented with pancytopenia as the prevailing manifestation. In addition, the presence of pancytopenia in leptospirosis is reviewed. In both patients, the outcome was favourable as the bone marrow aplasia reversed completely after treatment with intravenous penicillin. In conclusion, this case study suggests that Leptospira infection should be included in the differential diagnosis of febrile pancytopenia, even in the absence of classical signs of severe disease as jaundice, meningitis, renal failure and pulmonary infiltrates.

Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection: a pilot study.

AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-alpha), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-alpha, and the impact of these autoantibodies on the treatment outcome of HCV patients. METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs. RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy. CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN-alpha may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.