Mortality associated with standard prescription transfusions in cardiac surgery.

BACKGROUND: Before applying new blood management strategies, the extent of blood product transfusions and its correlation with perioperative mortality should be identified. METHODS: This study retrospectively analyzed the extent of perioperative transfusions of red blood cells (RBC), fresh frozen plasma (FFP), and platelets (PLT) in 565 consecutive cardiac surgery patients, who received transfusions based on standard prescriptions. Patients were stratified in four groups according to perioperative transfusion units (no transfusion, <5, 5-10, >10 units). Mortality was analyzed in relation to the type and extent of each blood product transfused and their combinations. Subsequently, the ability of transfusion volume to predict mortality was tested. RESULTS: Most patients received blood product transfusions perioperatively.  The observed mortality (11.7 %) correlated significantly with the volume of transfusion. Patients transfused with >5 RBC or FFP units or >10 PLT units had increased mortality compared with those receiving fewer transfusions (23.9 % vs 4.5 %, 27.4 % vs 6 %, 24.5 % vs 8.5 %, p <0.05, respectively). Analysis revealed that cutoffs of >5 units of RBC or >15 units of RBC, FFP, and PLT additively (sensitivity: 74.2 % and 72.7 %, specificity: 68.7 % and 69.5 %, respectively) had an acceptable discrimination ability for perioperative mortality (Area under the ROC curve: 0.756, p <0.001, and 0.735, p <0.001, respectively). CONCLUSIONS: This study confirmed a dose-dependent, transfusion-associated, increased mortality in cardiac surgery patients who received standard prescription transfusions. The results support the need for applying validated, patient-specific blood conservation strategies that correspond to the patient's actual perioperative transfusion needs. HIPPOKRATIA 2018, 22(2): 68-74.

Haemovigilance data on the use of methylene blue virally inactivated fresh frozen plasma with the Theraflex MB-Plasma System in comparison to quarantine plasma: 11 years' experience.

OBJECTIVES/BACKGROUND: Haemovigilance is an effective tool for identifying adverse effects of blood components. We analyse cumulative haemovigilance data in order to compare the two secured therapeutic plasmas that have been in use for more than 11 years in Greece - methylene blue-treated fresh frozen plasma (MB-FFP) and quarantine fresh frozen plasma (Q-FFP) - regarding safety and adverse events. METHODS/MATERIALS: Data from the centralised active haemovigilance system of Greece for the period 2001-2011 were used to examine the association between FFP types and adverse events. Post-transfusion information on infectious and non-infectious adverse events was analysed. Events were examined by reaction type, severity and imputability to transfusion. RESULTS: The incidence of adverse events was higher with Q-FFP (1:3620) than MB-FFP (1 : 24 593) by a factor of 6·79 [95% confidence interval (CI) 2·52-27·8]. Allergic adverse events were also commoner with Q-FFP (1 : 7489) than with MB-FFP (1:24 593), by a factor of 3·28 (95% CI 1·17-13·7). All adverse reactions experienced by the MB plasma recipients were considered to be mild. CONCLUSION: Haemovigilance over 11 years has demonstrated the long-term safety of MB-FFP in comparison to untreated quarantine FFP. In addition to lowering the adverse event rate, implementing the system on a national scale in at-risk countries would presumably reduce the transmission of severe viral infections including emerging infectious diseases by transfusion.

Factors that motivate and hinder blood donation in Greece.

Donations in Greece are insufficient to cover the high transfusion needs arising from large numbers of thalassaemia and sickle cell anaemia patients and the implementation of new surgical techniques. Efforts to achieve self-sufficiency, and to render blood supplies safer and manageable must focus on recruiting and retaining more volunteer donors and on converting the large pool of replacement donors. The aim of the study was to gain insight into public perception regarding the risks of donation and transfusion and to identify the factors that would motivate more people in Greece to regularly donate blood. Questionnaires were distributed to 1,600 donors at the blood bank and visitors to hospitals at 11 locations across the country. Data on demographics, donation behaviour, incentives, risk perception and attitudes towards donation and transfusion were analysed separately for volunteer and replacement donors and non-donors. The results showed that women and young people donate the least in Greece. Also, many donors do not donate because they are not reminded to. A small percentage of donors confessed to having concealed part of the truth to background questions. Overall, incentives to donate were considered important and included future availability of blood for self or family, paid leave from work and free blood tests. Recruitment and retention efforts should include better communication with current donors, and raising awareness among eligible donors. Staff should be educated in soliciting information from potential donors, and incentives should be better aligned to avoid conflict with ethical values and ensure honesty in the prescreening process.

Vasovagal reactions in blood donors during or immediately after blood donation.

The aim of the study was to estimate the type, incidence and causes of donor adverse reactions during and after blood donation in a Greek Blood Bank, where medical staff is responsible for donor selection. 12 173 blood donors were studied for adverse reactions. One-hundred and seven (0.87%) donors had a vasovagal reaction during or after blood donation. Donors who gave blood occasionally had a significant greater incidence of reactions compared with volunteer donors (1.15 versus 0.53%) (P < 0.001). There was no significant difference between men and women (0.85 versus 0.95%). First-time donors (1.7 versus 0.68%) and those under 30 years (1.15 versus 0.71%] had a significant greater possibility to have a reaction (P < 0.001). Twenty-two of 107 (20.5%) donors had a syncopal reaction. There was not a causative correlation of haematocrit, haemoglobin, systolic and diastolic blood pressure, pulse rate and weight in women (except weight in men) in developing a reaction. The stressing experience of phlebotomy was the reason for the higher frequency of a reaction. The incidence of reactions in our donors is lower than in other studies, and the possible reason for this is that only physicians are responsible for the selection of donors and trained personnel are careful of them during the donation process.

Markers of hepatitis viruses and human T-lymphotropic virus types I/II in patients who have undergone open-heart surgery: evidence of increased risk for exposure to HBV and HEV.

BACKGROUND: Open-heart procedure is characterized by a high-risk for contracting blood-borne infections. We evaluated the prevalence of several markers of hepatitis viruses (B-E) and human T-cell lymphotropic virus types I/II (HTLV-I/II) in a consecutive series of patients who had undergone open-heart surgery. METHODS: 204 patients and 158 selected age- and sex-matched healthy volunteers were investigated. Samples were collected at least 6-12 months postoperatively. Commercial enzyme immunoassays and confirmatory immunoblot assays for HCV, HEV and HTLV-I/II were used. RESULTS: None of the subjects tested positive for antibodies to HTLV-I/II. Prevalence of markers of past HBV infection and antibodies to HEV (anti-HEV) were higher in patients than in healthy controls (anti-HBc: 45.1% vs. 31%, p=0.009; anti-HBs: 31.9% vs. 22.2%, p=0.02; anti-HBe: 32.4% vs. 10.1%, p=0.000; anti-HEV: 5.4% vs. 0%, p=0.008). HBsAg and antibodies to HCV did not differ between the groups. CONCLUSIONS: HTLV, HBsAg and HCV infection markers did not differ between patients and healthy controls. However, patients had significantly increased prevalence of markers of previous HBV infection suggesting that an intensive vaccination schedule against HBV preoperatively might be helpful in minimizing the risk. The increased prevalence of anti-HEV in cardiac patients requires further investigation. Prospective studies are needed in order to definitely address whether the high prevalence of exposure to HBV and HEV infections in patients who had undergone open-heart surgery is procedure-related or not and whether it has any impact on morbidity of these patients.

Human T-lymphotropic virus type I/II infections in volunteer blood donors from Northern and Western Greece: increased prevalence in one blood bank unit.

BACKGROUND: Blood donors are routinely screened for antibodies to human T-cell lymphotropic viruses type I and II (HTLV-I and HTLV-II) in the United States, Canada, Japan, and some European countries. Previous reports from our group in relatively small numbers of donors have shown a zero prevalence of HTLV-I/II markers in our region. In this study, seven blood banks in the north and west of Greece participated in order to determine whether mandatory screening of blood donations for HTLV-I/II infection should be established. METHODS: Sera from 51,714 consecutive donors were investigated for anti-HTLV-I/II using two commercially available enzyme immunoassays (EIAs). Reactive samples in one or both EIAs were repeatedly evaluated further by Western blot, which is specific for both confirmation and differentiation of HTLV-I and HTLV-II seroreactivities. Investigation for HTLV DNA was also done in all EIA-reactive donors, irrespective of the WB result, using a combination assay based on the polymerase chain reaction (PCR) and a DNA EIA. RESULTS: A total of 115 donors (0.222%; 95% CI 0.018-0.26%) were initially considered reactive for anti-HTLV-I/II by EIAs. However, only 7 of the 115 were confirmed as positive by WB (five HTLV-I and two HTLV-I/II). Thus, the prevalence of anti-HTLV-I/II in donors from northern and western Greece was 0.013% (95% CI 0.003-0.023%). Interestingly, the majority of WB-confirmed anti-HTLV-positive individuals were detected in the blood bank of Corfu (5/7, all anti-HTLV-I). This prevalence (5/15383; 0.032%; 95% CI 0.004-0.061%) was six times the prevalence found at the other blood banks combined (2/36331; 0.0055%; 95% CI 0-0.013%), but it was not statistically significant. None of the EIA-reactive donors had detectable HTLV DNA. CONCLUSIONS: The very low prevalence of confirmed anti-HTLV-I/II infection markers in northern and western Greek blood donors, together with the negative PCR results in EIA-reactive subjects, indicates that anti-HTLV-I/I routine screening is not really justified in this area of our country. However, the increased prevalence of WB-confirmed anti-HTLV-I-positive donors in the Corfu blood bank calls for further prospective and careful investigation in order to address whether this finding represents a real cluster phenomenon of HTLV infection.

Hepatitis E virus antibodies in hemodialysis patients: an epidemiological survey in central Greece.

Hepatitis E virus (HEV) is the causative agent for enteric non-A, non-B hepatitis. Transmission is mainly via the fecal-oral route but the possibility of an additional parenteric transmission has been raised. Patients undergoing chronic hemodialysis (HD) have an increased risk of exposure to blood transmitted agents. Previous studies concerning prevalence of antibodies to HEV (anti-HEV) among HD patients gave conflicting results. The aim of the study presented here was to determine the prevalence of anti-HEV among HD patients of a well-defined semi-rural region in central Greece (Thessalia region). All patients (n=351, 234 males, mean age 60+/-14 years) who were being treated in the HD units of central Greece (n=5) during 2001 were tested for anti-HEV antibody. Two commercially available specific solid-phase enzyme-linked immunoassays were applied for anti-HEV detection. Hepatitis B virus markers, antibodies to HCV, HIV and HTLV were also screened in all patients by commercially available assays. Serum aminotransferase (AST, ALT) levels were measured by spectrophotometry. 17 anti-HEV-positive patients were found and prevalence was 4.8%, varying from 1.8 - 9.8% in the various HD units. Prevalence of HBsAg and anti-HCV was 5.7% (2.9 - 15%) and 23.6% (11.5 - 36.2%) respectively. The anti-HEV prevalence was increased compared to healthy blood donors in Greece (0.26%, p < 0.01). The highest prevalence of anti-HEV was seen at the HD unit of the General Hospital of Karditsa (9.8%). Risk factors for anti-HEV antibody were not identified: no association was found between anti-HEV positivity and age or sex, duration of HD, hepatitis B or C virus infection markers, previously elevated aminotransferase levels or history of transfusion. Our investigation of HEV infection in the cohort of HD patients in central Greece showed that the prevalence of anti-HEV was greater than in healthy blood donors. There was no association to blood borne infections (HBV, HCV). The high prevalence of anti-HEV we found in one HD unit was probably related to a local infection in the past. However, long-term prospective studies are needed in an attempt to identify whether intra-unit factors are also responsible for the increased prevalence of serologic markers of HEV infection among HD patients.

The prevalence of hepatitis C and hepatitis G virus infection in patients with B cell non-Hodgkin lymphomas in Greece: a Hellenic Cooperative Oncology Group Study.

Our aim was to investigate the association between chronic hepatitis C virus (HCV) infection and B cell non-Hodgkin lymphoma (NHL) in the Greek population. We studied 120 patients (70 men and 50 women, mean age 59 years) diagnosed with NHL. One hundred and eight had B cell NHL (90%) and 12 had T cell NHL (10%). The presence of anti-HCV antibodies in patients and controls was investigated using the monoclonal enzymatic immunoassay (MEIA) method. The detection of HCV RNA and hepatitis G virus (HGV) RNA in patients with B cell NHL and anti-HCV-positive controls was performed using an RT-PCR technique. Anti-HCV antibodies were present in only 2 of the 108 patients with B cell NHL (1.9%), while the prevalence of HCV infection in the healthy population was 0.6%, and in patients with various solid tumors treated with chemotherapy, it was 0.99%. Ten of the 108 B cell NHL patients (9.26%) were diagnosed as HGV RNA positive, while the prevalence of HGV infection in 285 Greek blood donors was 0.7%. Our findings do not confirm a strong association between HCV infection and B cell NHL for Greek patients. The increased prevalence of HGV infection detected in patients with NHL could imply the potential participation of HGV in the pathogenesis of NHL.

Low prevalence of HCV, HIV, and HTLV-I/II infection markers in northwestern Greece: results of a 3-year prospective donor study (1995-1997).

Background: The risk of infection with transfusion-transmitted viruses has been reduced remarkably. A zero-risk blood supply, however, remains a popular goal. A 3-year prospective donor study was conducted in the Epirus region of Greece to determine the prevalence of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus, and hepatitis C virus (HCV). Herein, we report the prevalence of HIV, HTLV, and HCV infection markers in this area. Methodology: Between January 1, 1995 and December 31, 1997, 6696 donors were investigated for the presence of anti-HIV, anti-HTLV, and anti-HCV antibodies using standard enzyme immunoassays (EIA). Every sample with anti-HCV reactivity by third-generation EIA was further investigated using a third-generation recombinant immunoblot assay (RIBA 3.0) and HCV-RNA by a combination of polymerase chain reaction (PCR) and DNA EIA. Results: None of the donors tested positive for anti-HIV or anti-HTLV antibodies. In contrast, anti-HCV was detected in 41 donors (0.61%). Using a RIBA 3.0 test, eight donors tested positive and eight had indeterminate results, while 25 tested negative. Seven of the eight donors with both EIA and RIBA 3.0 reactivity had increased levels of aminotransferases and detectable serum HCV-RNA. The remaining 34 donors had repeatedly normal aminotransferases and three times negative HCV-RNA. Liver biopsy was performed in anti-HCV/HCV-RNA-positive donors (7/41). The lesions were compatible with chronic hepatitis C in all of them. Conclusion: A zero prevalence of HIV and HTLV infection markers was found. Although the number of annual donations in this study was relatively low, the negative data for HIV and HTLV clearly indicate that rates of these infections are low in our region and that infected donors will be seen infrequently. HCV infection in blood donors remains very low in our region and is similar to the data reported in other industrialized countries. In fact, the prevalence of definite HCV infection seems to be very low (7/6696; 0.1%). However, a significant proportion of anti-HCV-reactive donors by third-generation EIA (33/41) had indeterminate or negative results by the RIBA 3.0. The latter donors were repeatedly negative for HCV-RNA. This finding may indicate that some donors tested false-positive for anti-HCV, although the possibility of true HCV infection contracted in the distant past cannot be excluded. In our opinion, close attention to mandatory principles of transfusion medicine, along with the screening of plasma donors using nucleic acid amplification technology, are the only methods that can further ensure the safety of our blood supply.

Cryoglobulinemia due to chronic viral hepatitis infections is not a major problem in clinical practice.

Background: Essential mixed cryoglobulinemia (EMC) is a systemic disease frequently associated with chronic viral hepatitis. This study was conducted in order to assess the prevalence of EMC in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. We also evaluated the possible associations of EMC with (1) the clinical, virological, and histological status of liver disease; (2) the presence of EMC-related symptoms; and (3) the response rate to interferon-alpha (IFN-alpha) treatment, in an attempt to address whether EMC is a major problem in hepatitis patients. Methodology: A total of 154 consecutive patients (104 with HBV and 50 with HCV infection) were investigated for the presence of rheumatoid factor (RF), cryoglobulins, and EMC-related manifestations. Sixty-two HBV patients were chronic carriers of hepatitis B surface antigen, 29 had chronic hepatitis B, and 13 HBV cirrhosis. Thirty-five HCV patients had chronic hepatitis C and 15 HCV cirrhosis. HCV genotyping was performed in 44 patients. Results: The prevalence of cryoglobulins was significantly higher (P<0.001) in HCV patients (46%) than in HBV patients (13.4%). EMC was associated with a high frequency of RF detection, older age, and longer duration of viral diseases. Weakness or malaise, arthralgias, and purpura were significantly more frequent in cryoglobulin-positive patients. These manifestations, however, were mild in most of the patients. The EMC-related symptoms were significantly associated with the presence of HCV infection, increased levels of cryoglobulins, and RF detection (P<0.01, P<0.05, and P<0.000005, respectively). Worse liver histology was unrelated to a higher prevalence or increased levels of cryoglobulins in both HBV and HCV infection. There was no relationship between EMC and a specific HCV genotype. IFN-alpha therapy led to the disappearance of cryoglobulins and EMC-related manifestations in most cases. The response rate to IFN-alpha was similar in both groups of patients (with and without EMC). Conclusions: A higher prevalence of EMC was observed in HCV patients than in HBV patients. However, this finding was unrelated to overt clinical manifestations of EMC, a specific HCV genotype, or worse liver histology. The latter suggests that EMC does not contribute to liver injury and vice versa, that EMC pathogenesis is rather unrelated to the degree of liver injury. From a clinical point of view, testing for cryoglobulins seems reasonable only for HCV patients with EMC-related manifestations, since this may have therapeutic consequences. RF detection could be used primarily as a surrogate marker for the existence of cryoglobulins.

Value of anti-HBc screening of blood donors for prevention of HBV infection: results of a 3-year prospective study in Northwestern Greece.

BACKGROUND: The risk of infection with transfusion-transmitted viruses has been reduced remarkably. However, a zero-risk blood supply remains a popular goal. Some authorities have introduced the screening for antibody to HBc (anti-HBc) as a surrogate test for the presence of several infectious agents. A 3-year prospective study was conducted in the Epirus region of Greece to determine the prevalence of several blood-borne viruses. One component of the study was the prevalence of HBV infection markers and the potential value of anti-HBc testing of donors in this area. STUDY DESIGN AND METHODS: Between January 1, 1995, and December 31, 1997, some 6696 donors were investigated for the presence of HBV infection markers by standard EIAS: Every sample that tested HBsAg-negative but anti-HBc-reactive alone or in combination with either or both antibodies to HBV e antigen (anti-HBe) and low-titered antibodies to HBsAg (anti-HBs <20 mIU/mL) was further investigated for the presence of HBV DNA by a combination of PCR and DNA EIA. RESULTS: Of these 6696 donors, 15.8 percent tested positive for at least one serologic marker of HBV infection (HBsAg prevalence, 0.85%). Anti-HBc reactivity alone or in combination with either or both anti-HBe and low-titered anti-HBs was found in 282 donors (4.2%). None tested HBV-DNA positive. No transfusion-associated HBV infections were recorded in the recipients of the above 282 blood units. CONCLUSION: A moderate prevalence of HBV infection markers was found. However, taking into account previous studies from this region, it appears that the HBsAg prevalence has declined. In addition, the present study cannot recommend the introduction of anti-HBc screening as a surrogate marker of occult HBV infection. The adoption of this exclusion criterion in this region would result in unacceptably high rejection rates among otherwise healthy donors. The absence of any case of transfusion-associated HBV infection after the transfusion of all HBsAg-negative, anti-HBc-positive units appears to provide further support for the negative HBV DNA results. Before a consideration of screening donors, efforts must be focused on reducing the number of false-positive anti-HBc results.

Interferon-alpha treatment of children with chronic hepatitis D virus infection: the Greek experience.

BACKGROUND/AIMS: The therapeutic experience of interferon-alpha therapy against hepatitis D virus infection in affected children is rather limited. For this reason, we conducted a retrospective study (duration: 1991-1995) in order to evaluate the efficacy and the safety of interferon-alpha in children suffering from chronic hepatitis D in Northwestern Greece. METHODOLOGY: Seven children who were found to be infected with HDV in a total of 324 children seropositive for hepatitis B virus infection during the 5-year period of the study were treated with interferon-alpha, 3 x 10(6) U/m2 body surface area, intramuscularly or subcutaneously, 3 times weekly for 1 year (after an informed consent obtained from their parents). Patients were assessed monthly by hematological serological and biochemical tests. Clinical progress, levels of serum alanine aminotransferase, hepatitis D ribonucleic acid (HDV-RNA) and hepatitis B deoxyribonucleic acid (HBV-DNA), seroconversion of hepatitis B surface antigen (HBsAg) and Hepatitis Be Antigen (HBeAg) and liver histology were used as response criteria. RESULTS: Posttreatment alanine transferase levels were significantly reduced (P < 0.05) but Immunoglobulin M and total anti-hepatitis D virus (anti-HDV) antibodies remained positive in all, while hepatitis D ribonucleic acid persisted positive in 4 cases. In addition, no seroconversion of HBsAg or HBeAg was noted and the liver histology progress was disappointing. Side effects including mild fever, arthralgias and malaise and reversible neutropenia and thrombocytopenia were common, but not particularly disturbing. Nevertheless, the children remained fully active on treatment, felt well and attended school. Initially 4 children had been below the 10th percentile for weight and height. All thrived during treatment and two crossed above the 10th percentile indicating height velocity and body mass index increase. CONCLUSIONS: The administration of regular interferon-alpha doses for treating children with chronic hepatitis D was safe as attested by the mild side effects and the objective clinical criteria regarding their growth, but relatively ineffective. Although the prevalence of hepatitis D virus infection is now generally decreased, this study indirectly indicates that more effective agents and new approaches at the molecular level of the hepatitis D virus genome are urgently warranted for its control in individuals already infected with the virus. Finally, the poor therapeutic results in the present study further enhance the necessity of the expanded vaccination against Hepatitis B virus according to the World Health Organization's recommendations.

Increased incidence of anti-cardiolipin antibodies in patients with hepatitis C is not associated with aetiopathogenetic link to anti-phospholipid syndrome.

OBJECTIVE: Chronic infection with hepatitis C virus (HCV) has been found to be associated with various diseases known as extra-hepatic manifestations of HCV. Recently, HCV has been implicated as a cause of the antiphospholipid syndrome (APLS). We conducted a study in a well-characterized area for epidemiological and prospective studies in the north-western part of Greece in order to address whether an aetiopathogenesis exists between HCV and APLS. DESIGN: Seventy-five patients with chronic hepatitis C were investigated for the presence of anti-cardiolipin antibodies (anti-CL) and for a past medical history supportive to the diagnosis of APLS. In addition, 24 patients with well-defined APLS (primary or secondary) and 12 patients with systemic lupus erythematosus (SLE) were tested for the presence of markers of HCV infection (anti-HCV and HCV RNA). The SLE patients were anti-CL-positive but none of them had developed any of the known clinical features of APLS. In addition, 267 healthy subjects were investigated for the presence of anti-CL. METHODS: IgG and IgM anti-CL were determined by a quantitative isotype-specific solid phase enzyme-linked immunosorbent assay set up in our laboratory. Anti-HCV was determined using a third-generation enzyme immunoassay and a confirmatory third-generation recombinant immunoblot assay. Active virus replication was defined by the detection of HCV RNA using a combination assay based on a reverse transcriptase polymerase chain reaction and a DNA enzyme immunoassay. RESULTS: Of the HCV patients, 37.3% had IgG and/or IgM anti-CL (P<0.00005 compared to healthy controls (2.25%)). However, the mean titres of each specific isotype were significantly lower in HCV patients compared with those found in the APLS patients (P<0.05 for IgM and P<0.001 for IgG isotypes). The mean titres of IgG anti-CL were also significantly lower in HCV patients compared with those found in the SLE patients (P<0.01). All patients with APLS or SLE (n = 36) tested negative for HCV infection markers. In addition, neither thrombotic events nor thrombocytopenia were associated with a positive anti-CL test in HCV patients. CONCLUSIONS: A significant proportion of HCV patients (37.3%) had detectable anti-CL of low titre. However, this finding was not associated with the development of APLS. On the other hand, none of the APLS patients was positive for HCV. Taken together, our data rather failed to reveal an aetiopathogenetic link between HCV and APLS. For this reason, testing for HCV in patients with APLS or follow-up for the possibility of the development of APLS in HCV patients cannot be suggested, at least in Greek patients. More prospective studies of longer duration are required in order to address whether HCV is involved or not in the aetiopathogenesis of APLS.

Antibodies to hepatitis E virus among several populations in Greece: increased prevalence in an hemodialysis unit.

BACKGROUND: Hepatitis E virus (HEV) has been found to be the causative agent of enterically transmitted non-A, non-B hepatitis in tropical and subtropical countries. Several investigators, however, have indicated that HEV could be endemic in Europe, albeit at a low prevalence. STUDY DESIGN AND METHODS: The purpose of this study was to estimate the prevalence of anti-HEV in various populations in northwestern Greece (Epirus region). Healthy blood donors (2636), refugees from southern Albania (350), children (165), injecting drug users (IDUs) (65), multiply transfused patients (62), patients with chronic viral hepatitis (75), and chronic hemodialysis patients (149) were investigated for anti-HEV by enzyme immunoassay and confirmatory Western blot assay. In addition, 380 consecutive healthy blood donors and 62 hemodialysis patients from a neighboring area (Agrinion, Greece) were investigated. RESULTS: A very low presence of anti-HEV antibody was found among healthy blood donors from Epirus (0.23%) and Agrinion (0.53%). Anti-HEV was not detected in children, IDUs, or multiply transfused patients. In contrast, a low but significant prevalence of anti-HEV was found among refugees (4.85%), patients with chronic viral hepatitis (5.3%), and hemodialysis patients from Epirus (1.34%), as compared with healthy blood donors from Epirus: p < 0.0001, p < 0.00001, and p < 0.10, respectively. A high prevalence (9.7%) of anti-HEV was revealed in patients at the hemodialysis unit of the General Hospital of Agrinion (p < 0.00005, compared to healthy blood donors from Agrinion). No significant association was found between anti-HEV positivity and the age or sex of donors, the duration of hemodialysis, positivity for hepatitis B or C virus infection markers, history of hepatitis, increased alanine aminotransferase, renal transplantation, a history of transfusion, or the number of units transfused. CONCLUSION: This study demonstrated a high prevalence of anti-HEV in a separate hemodialysis unit, without an association with the known routes of transmission of blood-borne viruses. This observation suggests that a still-undefined intra-unit factor or other factors are associated with HEV transmission.

Absence of HCV viraemia in anti-HCV-negative haemodialysis patients.

BACKGROUND: Immunologic alterations have been reported in chronic haemodialysis (HD) patients. Some HD patients may have, therefore, an inability to produce detectable amounts of serum antibodies to hepatitis C virus (anti-HCV). Previous studies have shown the presence of HCV viraemia in anti-HCV-negative HD patients (ranging from 1 to 15%). However, the universal epidemiologic impact of these cases remains uncertain since there are conflicting results. In this context, we conducted a study in an attempt to investigate the presence of HCV viraemia among anti-HCV-negative HD patients in a well-defined geographic area of the northwestern part of Greece. METHODS: During a 6 month period, 81 anti-HCV-negative HD patients were tested twice for the presence of HCV RNA, using the reverse transcriptase polymerase chain reaction (RT-PCR) combined with a DNA enzyme immunoassay (DEIA). At the same time, periodic testing for anti-HCV by two commercially available third generation assays was done. In addition, 15 anti-HCV-positive HD patients and 20 non-HD patients with well established chronic HCV infection used as internal controls were tested for the presence of HCV RNA and anti-HCV. RESULTS: None of the anti-HCV-negative HD patients were shown to be viraemic by the combined RT-PCR and DEIA method. During the same time period, all remained anti-HCV negative by the third generation assays. By contrast, all the patients with known HCV-infection were positive by the two enzyme immunoassays, whereas 13 anti-HCV-positive HD patients (86.7%) and 18 non-HD patients (90%) were viraemic by RT-PCR. CONCLUSIONS: This study demonstrated that routine HCV RNA testing in anti-HCV-negative HD patients appears not to be necessary particularly when third generation assays are used for the detection of anti-HCV.

A prospective evaluation of dermatological side-effects during alpha-interferon therapy for chronic viral hepatitis.

OBJECTIVE: Alpha-interferon therapy may occasionally account for immune-mediated phenomena. This study was conducted in an attempt to investigate the incidence of the development of immune-mediated dermatological diseases during alpha-interferon therapy in patients with chronic viral hepatitis. The latter has not been evaluated prospectively, whereas most of the previous studies examined small numbers of interferon treated patients or consisted of case reports. DESIGN: A prospective case-control study. SETTING: A tertiary referral centre. PARTICIPANTS: One hundred and twenty consecutive patients with chronic viral hepatitis (67 with hepatitis B, 45 with hepatitis C, six with both hepatitis viruses, and two with delta hepatitis) were evaluated during a course of alpha-interferon therapy. In addition, 120 consecutive patients with chronic liver diseases (disease control group), who had never received alpha-interferon therapy, were evaluated during the period of the study (at least for 12 months). INTERVENTIONS: Recombinant alpha-interferon at a dose of 4.5 or 5 million units subcutaneously (s.c.) three times per week for 6 to 12 months was administered to patients with hepatitis B. The patients with chronic hepatitis C were treated with 3 million units s.c. three times per week for 12 to 18 months. The patients with chronic hepatitis B and C infections received 4.5 million units for 6 months, and then 3 million units for an additional 6 to 12 months. Finally, the patients with chronic delta hepatitis received 5 million units for 1 year or more. MAIN OUTCOME MEASURES: To assess prospectively the incidence of these dermatological disorders during alpha-interferon therapy and to estimate if there is any relationship between their development and the clinical, laboratory or other characteristics of the patients with chronic hepatitis. RESULTS: Three to 6 months after the initiation of alpha-interferon three patients with chronic viral hepatitis (two with hepatitis C and one with hepatitis B) developed lichen planus, whereas one patient with hepatitis C developed relapsing aphthous stomatitis. The development of these disorders was significantly associated only with the presence of antinuclear antibodies before the initiation of alpha-interferon (P=0.000000). None of the patients from the disease control group had such a manifestation during the follow-up. Lichen planus resolved after the end of therapy in all of them. In contrast, therapy was discontinued in the patient who developed aphthous stomatitis, owing to the painful lesions. CONCLUSIONS: This study demonstrated that alpha-interferon may rarely (3.3%) induce immune-mediated dermatological disorders, especially lichen planus. The development of these disorders may reflect a subclinical or covert autoimmune background of patients, as suggested by the presence, although in low titres, of antinuclear antibodies. However, when lichen planus developed, it was mild, did not require the discontinuation of therapy and resolved after alpha-interferon administration had ceased.

Idiopathic dilated cardiomyopathy: lack of association with hepatitis C virus infection.

OBJECTIVE: To determine whether there is an association between hepatitis C virus (HCV) infection and dilated cardiomyopathy in a well defined area of north western Greece; such an association has been reported elsewhere. DESIGN: Evaluation of consecutive patients with chronic HCV infection for the presence of clinical or subclinical manifestations of dilated cardiomyopathy by history, physical examination, and non-invasive laboratory procedures (ECG, chest x ray, and echocardiography) before the initiation of interferon alpha treatment; investigation for HCV infection markers in patients with dilated cardiomyopathy by enzyme and immunoblot assays (antibodies to HCV) and the reverse transcriptase polymerase chain reaction (HCV RNA). SETTING: A tertiary referral centre for patients with chronic hepatitis and dilated cardiomyopathy. PATIENTS: 102 patients with well defined chronic HCV infection and 55 patients with well established dilated cardiomyopathy were evaluated. MAIN OUTCOME MEASURES: The need for HCV testing in patients with dilated cardiomyopathy, or follow up for heart disease in patients with chronic HCV infection. RESULTS: None of the patients with chronic HCV infection had clinical or subclinical evidence of dilated cardiomyopathy from history and laboratory findings. None of the patients with dilated cardiomyopathy was positive for antibodies to HCV or viraemic on HCV RNA testing. CONCLUSIONS: The study neither confirms the findings of other investigators, nor indicates a pathogenic link between HCV and dilated cardiomyopathy. For this reason, at least in Greece, testing for HCV in patients with dilated cardiomyopathy or follow up for heart disease in HCV patients appears unnecessary. Genetic or other factors could be the reason for this discrepancy if previously reported associations between HCV and dilated cardiomyopathy or hypertrophic cardiomyopathy were not coincidental.

Blood salvage after total hip and total knee arthroplasty.

We performed a prospective study to determine the effect of postoperative collection and reinfusion of unwashed, filtered, salvaged blood alone and in combination with preoperative predeposited blood on the transfusion requirements of 375 patients treated with a total hip or total knee replacement. 208 patients were managed with postoperative blood salvage with use of the CBC ConstaVac autotransfusion system and closed suction drainage. Another 50 patients predeposited 1-4 units of autologous blood, before the operation, in addition to postoperative blood salvage. The remaining 117 patients were used as controls and were transfused with homologous blood from the blood bank. Postoperative reinfusion of salvaged blood decreased the need for homologous transfusion after hip and knee arthroplasty (mean 2.7 units) compared to controls (mean 4.2 units). The combination of postoperative reinfusion of salvaged blood and predeposited autologous blood was associated with the lowest requirements for homologous blood transfusions (mean 1.7 units).