Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.

BACKGROUND: A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses. AIM: To determine clinical, histological, virological and immunological markers 5-20 years after SVR. METHODS: In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation. RESULTS: Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies. CONCLUSIONS: Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.

Nosocomial hepatitis C in a thoracic surgery unit; retrospective findings generating a prospective study.

We describe the transmission of hepatitis C virus (HCV) to two patients from a thoracic surgeon who was unaware of his hepatitis C infection. By partial sequencing of the non-structural 5B gene and phylogenetic analysis, the viruses from both patients were found to be closely related to genotype 1a strain from the surgeon. Two further hepatitis C cases were found in relation to the thoracic clinic. Their HCV sequences were related to each other but were of genotype 2b and the source of infection was never revealed. To elucidate the magnitude of the problem, we conducted a prospective study for a period of 17 months in which patients who were about to undergo thoracic surgery were asked to participate. Blood samples were drawn prior to surgery and at least four months later. The postoperative samples were then screened for anti-HCV and, if positive, the initial sample was also analysed. The only two patients (0.4%) identified were confirmed anti-HCV positive before surgery, and none out of 456 evaluable cases seroconverted to anti-HCV during the observation period. Despite the retrospectively identified cases, nosocomial hepatitis C is rare in our thoracic unit. The study points out the risk of transmission of hepatitis C from infected personnel and reiterates the need for universal precautions.

Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases.

AIMS: To investigate whether hyperechogenicity of liver can reliably be interpreted as liver steatosis and if any concomitant or isolated fibrosis can be disclosed. PATIENTS AND METHODS: A series of 165 patients with no signs or symptoms of liver disease referred because of slightly to moderately raised aminotransferases (alanine aminotransferase and/or aspartate aminotransferase 0.7-5.0 microkat/l) for more than 6 months were prospectively investigated with a comprehensive laboratory profile, ultrasound examination of liver and percutaneous liver biopsy Fibrosis was assessed quantitatively and according to Metavir. Steatosis was graded as none, mild, moderate or severe. RESULTS: Of 98 (59.4%) patients with raised echogenicity, 85 (86.7%) had liver steatosis of at least moderate degree, 9 patients with same degree of steatosis had normal echogenicity and 13 patients with no or only mild steatosis had a hyperechogenic liver (sensitivity 0.90, specificity 0.82, positive predictive value 0.87, negative predictive value 0.87). About the same relations were found regardless of body mass index and degree of fibrosis. With increased echogenicity together with high attenuation (n = 591 and reduced portal vessel wall distinction (n = 79), positive predictive value increased to 0.93 and 0.94, respectively. Quantitatively assessed fibrosis (mean +/- SD) was 3.2 +/- 4.6% of biopsy area with normal and 2.3 +/- 1.8% with raised echogenicity (ns). Echogenicity was normal in 5 out of 9 patients with septal fibrosis and in 4 out of 6 patients with cirrhosis. Any structural, non-homogenous findings at ultrasound were not associated with architectural fibrotic changes and none had nodular contours of liver surface. CONCLUSIONS: Assessment of liver echogenicity is of value for detection or exclusion of moderate to pronounced fatty infiltration (correct classification 86.6%) but cannot be relied upon in diagnosing fibrosis, not even cirrhosis in asymptomatic patients with mild to moderately elevated liver transaminases.

High serum hepatocyte growth factor levels in the acute stage of community-acquired infectious diseases.

Acute serum levels of hepatocyte growth factor (HGF) were studied in 6 clinical groups with (i) gastroenteritis, (ii) skin and soft tissue infection, (iii) urinary tract infection, (iv) septicemia, (v) influenza, and (vi) chronic hepatitis C in comparison with a normal control group using an enzyme-linked immunosorbent assay method. We found that serum HGF levels were significantly higher in patients with acute infectious diseases (p < 0.0001) compared to patients with chronic viral hepatitis and healthy controls. Serum HGF and CRP levels were correlated significantly (r=0.65, p < 10(-7)). We conclude that serum HGF levels are elevated in patients with acute infectious diseases.

Interaction of Staphylococcus epidermidis from infected hip prostheses with neutrophil granulocytes.

This study focuses on the interaction of Staphylococcus epidermidis isolated from granulation tissue covering infected hip prostheses and neutrophil granulocytes. Bacterial strains isolated from normal flora were used as controls. The bacteria were well characterized with routine methods and further characterized with random amplified polymorphic DNA analyses and slime tests. Phagocytosis and chemiluminescence (CL) assays were used in the neutrophil interaction studies. The prostheses strains were ingested to a lesser extent than strains from normal flora (p < or = 0.001). There was no significant difference between the prostheses strains and the normal flora strains in terms of total CL response. However, the extracellular CL response from the neutrophils was lower in comparison with the normal flora when interacting with the prostheses strains. The results of this study support the notion that S. epidermidis strains isolated from infected hip prostheses have an enhanced capacity to resist phagocytosis and that most of these strains elicit a reduced inflammatory response, measured as the production of extracellular oxidative metabolites from the neutrophils, compared to normal flora.

Liver guide for monitoring of chronic hepatitis C.

The severity of chronic hepatitis C infection in the individual patient is monitored using blood laboratory findings and liver biopsy. If blood test results could be shown to provide sufficient information concerning the disease, the invasive procedure of liver biopsy could perhaps be avoided in some instances. This study assessed the clinical relevance of blood laboratory tests for detecting disease-related changes in the liver. Histopathological classification was used to assign class membership of the patients and data mining operations were performed in an elaborate way on 19 different data sets. Disease activity could be detected by a small set of blood tests. Extended sets could identify more severe changes, but failed to distinguish them. The extracted rules are implemented as a part of the knowledge base of a corresponding decision support system aimed at specialists and general practitioners.

Platelets enhance neutrophil locomotion: evidence for a role of P-selectin.

It has been suggested that the accumulation of platelets at sites of vascular damage and inflammation regulates the function of leukocytes. In this study, we investigated the effects of platelets on the transmigration of neutrophil granulocytes through microporous membranes. We demonstrate that platelets markedly enhance both the random and the chemotactic migration of neutrophils. Stimulatory effects were acquired by adding paraformaldehyde-fixed platelets or the supernatants of platelets; however, the effects were lower or significantly higher, respectively, compared with viable platelets. The increased neutrophil migration was associated with an amplified polymerization of actin filaments and expression of CD11b/CD18. Previous investigations indicate that the initial adhesion between platelets and neutrophils is mediated by P-selectin exposed on the surface of platelets. In this study, the following observations suggest a role for P-selectin in the platelet-induced enhancement of neutrophil motility: (i) platelet supernatants contained substantial amounts of P-selectin, (ii) filtration of platelet supernatants markedly reduced the content of P-selectin and simultaneously decreased the potentiating effects on neutrophil motility, (iii) inhibition of P-selectin-mediated cell cell adhesion with sialyl Lewis X or by incubation in calcium-free medium reduced the enhancing effects of platelets on neutrophil responses, and (iv) purified and recombinant P-selectin mimicked the effects of platelets on neutrophil locomotion. In conclusion, we propose that platelets through P-selectin promote accumulation and emigration of neutrophils during inflammatory and thrombotic processes.

Influence of pre-treatment factors on outcome of interferon-alpha treatment of patients with chronic hepatitis C.

A total of 172 Swedish patients treated with interferon-alpha for at least 24 weeks and followed-up > or =24 weeks after treatment was stopped were analysed for pre-treatment factors of importance for achieving a virological sustained response (SR). Furthermore, the predictive value for a virological SR of a positive or negative HCV RNA test at week 12 of treatment was evaluated. A low baseline viral load and genotype non-1b were pre-treatment factors indicating a favourable response. Thus, 44% (38/86) of patients with a low baseline viral load vs. only 16% (14/86) of those with a high viral load had a virological SR (p<0.0001). Of patients with a negative qualitative HCV RNA test after 12 weeks of interferon treatment, 46% (44/95) had virological SR, whereas only 5.9% (4/68) of those with a positive test had (p<0.0001). Prolonged ( > 6 months) treatment with interferon-alpha tended to increase the chance of virological SR (p<0.052).

Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise.

Health care workers at risk for hepatitis B virus infection are recommended for vaccination. Low-dose intradermal (i.d.) administration of vaccine has been suggested as a less expensive alternative to intramuscular (i.m.) inoculation. To evaluate the i.d. vaccination route, health care workers were included in a prospective study. The subjects were vaccinated with 0.1 ml (= 2 microg) recombinant vaccine (Engerix B, SmithKline Beecham) i.d. at 0, 1 and 6 months. Two months after the third vaccination, measurement of the anti-HBs level was conducted. An anti-HBs level > or =10 IU/l was considered protective. Those with an anti-HBs level <10 IU/l were given a fourth dose with new serological control after another 2 months. The results are based on the 1406 subjects that it was possible to evaluate. The seroconversion rate to protective anti-HBs level after 3 doses was 68% and after 3 or 4 doses 89%. Factors associated with a lower response rate were increasing age (p<0.05) and smoking (p<0.001). Sex or body mass index had no influence on the results. Vaccination technique seems to be of utmost importance when the i.d. route is used. Well instructed and experienced nurses are required and quality control with follow-up of overall seroconversion rate within each centre is needed.

Long-term follow-up of chronic hepatitis C patients with sustained virological response to alpha-interferon.

BACKGROUND/AIMS: This study aimed to determine the long-term outcome of hepatitis C virus (HCV)-infected patients who respond to interferon treatment with clearance of serum HCV RNA. METHODS: We performed a long-term biochemical, virological, and histological follow-up of all sustained virological responders, defined as those who became HCV RNA negative at follow-up 6 months after the end of treatment, from 3 controlled interferon trials performed in Sweden between 1988 and 1994. RESULTS: At biochemical and virological long-term follow-up performed in 26 sustained virological responders 3.5-8.8 years (mean +/- SD, 5.4+/-1.6 years) after the end of IFN therapy, 22 patients (85%) had normal serum ALT levels, and 24 patients (92%) were HCV RNA negative in serum. Liver biopsies performed in 23 patients 2.1-8.7 years (mean +/- SD, 5.0+/-1.8 years) after end of treatment showed no or minimal inflammation, whereas mild and probably irreversible fibrosis was seen in a few patients. CONCLUSION: In this well-defined material of sustained responders to IFN therapy, the long-term prognosis was excellent. Nearly all had a durable response, not only biochemically and virologically, but more importantly also histologically with normalisation or near normalisation of previous histological lesions.

The clinical significance of slightly to moderately increased liver transaminase values in asymptomatic patients.

BACKGROUND: Our aim was to study liver disorders in asymptomatic patients with slightly to moderately increased liver transaminase values in a population living in an area with a low prevalence of viral and hereditary liver diseases. METHODS: One hundred and fifty consecutive patients with slightly to moderately increased liver transaminases for at least 6 months without symptoms or signs of liver disease were included. Median (range) was 0.75 microkat/l (0.24-2.9) for aspartate aminotransferase (ASAT) and 1.18 microkat/l (0.28-4.5) for alanine aminotransferase (ALAT). A percutaneous liver biopsy was performed, and blood was sampled for a detailed biochemical and serologic profile. RESULTS: Chronic viral hepatitis C was found in 15.3% of the patients, autoimmune hepatitis in 1.3%, primary biliary cirrhosis in 1.3%, and heterozygotic alpha-1-antitrypsin deficiency in 0.7%. Presumed alcoholic liver disease was diagnosed in 8%, and non-alcoholic steatohepatitis in 2%. Chronic hepatitis with no obvious etiology was diagnosed in 24%, of whom 39% had interface hepatitis (piecemeal activity). Seventy-one per cent of these 39% had measurable levels of autoantibodies, but IgG levels within normal limits prevented the 'clinical' diagnosis of autoimmune hepatitis. Liver steatosis was the diagnosis in 40%. Most were overweight and had increased serum triglyceride levels. However, in 13.3% the fatty infiltration was considered 'essential', as both body mass index (BMI) and triglyceride levels were normal. Other diagnoses were liver fibrosis with no obvious inflammatory activity (3.3%), cirrhosis of unknown etiology (0.7%), and for the remaining (3.3%) patients histopathologic findings were considered 'normal'. Cirrhosis was found in five biopsy specimens: hepatitis C (n = 2), autoimmune hepatitis (n = 1), primary biliary cirrhosis (n = 1), and cryptogenic cirrhosis (n = 1). No concomitant disease was of importance for the diagnosis and/or histopathologic findings. No obvious drug-related increased liver test results were found with any single drug. However, patients with chronic hepatitis of unknown etiology, especially with interface hepatitis, significantly more often than the rest of the population were receiving drug treatment. CONCLUSION: Most transaminitis patients had steatosis, and some had defined diseases including chronic hepatitis C. Chronic hepatitis of unknown etiology was found in a substantial proportion (24%) of a population living in an area with a low burden of hepatic viruses and genetic disorders.

Take care: guidelines for patients with chronic hepatitis C.

Alcohol consumption has significant impact on the condition of the liver, by itself, and even more in conjunction with other liver diseases such as chronic hepatitis C. Drinking habits might be delicate issues to address and could harm otherwise satisfying communication. Therefore, we intended to outline guidelines for advising hepatitis C patients concerning alcohol consumption. Analysis of a relatively limited knowledge base revealed the complexity of the disease rather than statistically significant findings regarding consumption. Thus, we instead chose to suggest a set of patient educational guidelines, which could be implemented on the Internet, hypothesizing that a better informed patient will be more able to comply with restrictions concerning alcohol consumption. A brief ad hoc evaluation pointed out Internet as a favourable media to present the information. We also suggest a tentative algorithm for further development of clinical decision support systems addressing monitoring of chronic hepatitis C patients.

GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors.

Sera from 62 hepatitis C virus (HCV)-infected Swedish blood donors were tested by a nested polymerase chain reaction using primers targeting the 5'-noncoding region of the GB virus-C/hepatitis G (GBV-C/HGV) genome and an enzyme-linked immunosorbent assay that detects antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). Fourteen (22%) and 21 (34%) of the 62 blood donors were found to be GBV-C/HGV RNA and anti-E2 positive, respectively. None of the blood donors was positive for both GBV-C/HGV RNA and anti-E2. Thus, 35 of 62 (56%) HCV-infected donors had been exposed to GBV-C/HGV infection. At sequencing of the 14 GBV-C/HGV isolates, 12 were identified as subtype 2a and 2 as subtype 2b. One of 7 (14%) donors with mild liver disease such as steatosis and nonspecific reactive hepatitis had been exposed to GBV-C/HGV vs. 34 of 55 (62%) with chronic hepatitis with or without cirrhosis (P = 0.04). All other differences in histology were small between HCV and dual HCV GBV-C/HGV-infected donors. In conclusion, more than half of HCV-infected Swedish blood donors in this study were positive for either GBV-C/HGV RNA or anti-E2. GBV-C/HGV viremia and seropositivity were mutually exclusive.

Randomised, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. The Swedish Study Group.

BACKGROUND: Pilot studies suggested that more patients with chronic hepatitis C virus (HCV) infection had a sustained virological response when treated with the combination of interferon alpha-2b and ribavirin than with interferon alpha-2b alone. We investigated the biochemical and virological responses and safety of treatment with interferon alpha-2b and ribavirin compared with interferon alpha-2b alone. METHODS: In this double-blind trial 100 patients were randomly assigned to treatment with interferon alpha-2b (3 MU three times a week) in combination with ribavirin (1000 or 1200 mg per day) or placebo for 24 weeks and then followed up for a further 24 weeks. A further follow-up was done 1 year after active treatment stopped. The primary endpoint was the sustained virological response, defined as no detectable HCV RNA by PCR at both week 24 and week 48. Retrospectively, the baseline HCV-RNA load was analysed as a predictor of a sustained virological response. Data were analysed by intention to treat. FINDINGS: 18 (36%) of the 50 patients in the interferon alpha-2b and ribavirin group had a sustained virological response compared with nine (18%) of the 50 patients in the interferon alpha-2b and placebo group (p = 0.047). At the 1 year follow-up the proportion of patients with a virological response was greater in the interferon alpha-2b and ribavirin group than the interferon alpha-2b and placebo group (42 vs 20%, p = 0.03), respectively. More patients with baseline HCV-RNA concentrations greater than 3 x 10(6) genome equivalents (Eq) per mL had a sustained response with interferon alpha-2b and ribavirin than with interferon alpha-2b and placebo (12/29 vs 1/26, p = 0.009), whereas the sustained response did not differ between the two treatment groups for HCV-RNA amounts less than 3 x 10(6) Eq per mL (6/21 vs 8/24, p = 0.67), respectively. INTERPRETATION: More patients with chronic hepatitis C have a sustained virological response with interferon alpha-2b and ribavirin than with only interferon alpha-2b treatment. We suggest that patients with high HCV-RNA loads should be treated with interferon alpha-2b and ribavirin.

Comparison of 3 quantitative HCV RNA assays--accuracy of baseline viral load to predict treatment outcome in chronic hepatitis C.

The correlation between 3 assays for hepatitis C virus (HCV) RNA quantification and their respective accuracy in predicting the response to interferon and interferon/ribavirin therapy was evaluated by analysing pre-treatment sera from 100 patients. A total of 97%, 100%, and 98% of the patients tested positive by the branched DNA 2.0 assay (Quantiplex), a multi-cycle reversed transcriptase polymerase chain reaction quantitative assay (Superquant) and the Roche Amplicor Monitor assay, respectively. The correlations between the assays, in all patients and in the major genotypes 1, 2, and 3, were significant, although the levels detected by the Amplicor Monitor assay were more than 1 log lower than by the other assays. Sustained virological responders to interferon therapy, but not to combination therapy, had lower baseline viral levels than long-term non-responders (p = 0.002 by Quantiplex 2.0; p = 0.008 by Superquant; p = 0.06 by Roche Amplicor Monitor). Pre-treatment viral load greater than 3 x 10(6) Eq or copies/ml by the Quantiplex 2.0 and Superquant assays and greater than 100,000 copies/ml by the Amplicor Monitor assay predicted long-term non-response in 94%, 93% and 91% of the interferon treated patients, respectively. In conclusion, acceptable correlations between available commercial quantitative assays were found. High baseline viral load predicted long-term non-response to interferon monotherapy, whereas it did not to interferon/ribavirin combination therapy.

[Care of a patient with a rare and highly contagious virus disease. An emergency situation resulted in good preparedness]. / Vård av patient med exotisk högsmittsam virussjukdom. Akut läge gav bra beredskap.

Ever since the eradication of smallpox, Sweden has been poorly furnished with emergency facilities for the care of patients with serious, very infectious diseases. National interest in creating such facilities was aroused by epidemics of haemorrhagic disease (first and foremost due to Ebola virus during the present decade), at the same time as the first Scandinavian case of haemorrhagic fever associated with a risk of person-to-person infection occurred in Linköping. A special laboratory which has been set up at the Centre for Disease Control, in Stockholm, and University Hospital, Linköping, in collaboration with the Board of Health and Welfare, has introduced a high-security infectious disease unit for the care of such patients, with separate ventilation and waste-water treatment systems. The unit is also equipped to provide intensive care, and a laboratory can be rapidly set up and fully operative within 12-24 hours. Most important of all, personnel are available who are trained both for laboratory work and the care of such patients, and used to working as a team and familiar with the special protective equipment. If a patient can not be transported to the special unit, a team is available to travel to the hospital where the patient has been admitted, to give instruction and help to set up infection control routines and even supply protective equipment.

Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.

BACKGROUND/AIMS: Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24-week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo. METHODS: A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was administered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention-to-treat population: 76 received ribavirin and 38 placebo. RESULTS: Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5%) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (p < 0.001). ALT levels were normal in 22/76 (29%) of ribavirin-treated patients vs 0/38 placebo recipients (p < 0.001). Twenty-four weeks after stopping ribavirin, the majority of patients had abnormal ALT levels. There was no difference between the treatment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than placebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p = 0.05). Ribavirin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (p < 0.001). CONCLUSIONS: These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not significantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited.

Hepatitis C virus transmission, 1988-1991, via blood components from donors subsequently found to be anti-HCV-positive.

The recipients of blood components, from the first 12 anti-hepatitis C virus (HCV) positive donors identified by blood donor screening, 1985-1991, were traced retrospectively and tested to assess the HCV transmission rate, HCV genotypes and disease severity. Three enzyme-linked immunosorbent assay (ELISA) positive but RIBA-indeterminate and HCV RNA-negative donors did not transmit HCV to their 9 traced recipients. Nine RIBA- and HCV RNA-positive donors had donated blood to 27 now living recipients of whom 16/27 (59%) were viraemic 1-5 years later. Nine recipients had resolved infection, as determined by PCR HCV RNA. Five of these were RIBA-2 positive but HCV RNA-negative and 4 recipients were RIBA-2-indeterminate and HCV RNA-negative. Two recipients negative in all tests had probably received blood before the donor became infected with HCV. The HCV genotype in each case was identical between the donor and the recipient. Of the viraemic recipients, 50% (8/16) were unsuitable for further investigation or therapy due to their high age and/or underlying severe disease. At most, only 30% (8/27) of the recipients were suitable for further investigation and/or treatment. Two of these were already diagnosed as being infected with HCV before being traced. It is concluded that the benefit of a general tracing of recipients of blood components from HCV-infected donors is doubtful since only a few of them are suitable candidates for treatment. Our results seem to indicate that it is more appropriate to recommend anti-HCV testing to those seeking medical care who have received transfusions or undergone major surgery before 1992, i.e. before anti-HCV-screening was initiated.

HCV genotypes in Swedish blood donors as correlated to epidemiology, liver disease and hepatitis C virus antibody profile.

Sixty-two anti-HCV and HCV-RNA positive Swedish blood donors (44 men, 18 women; median age 34 years) were studied. HCV genotypes were correlated to parenteral risk factors, liver morphology, serum alanine aminotransferase (ALAT) levels and HCV antibody profile. Forty percent of the donors were infected with HCV genotype 1a, 10% with 1b, 21% with 2b, and 29% with 3a. Intravenous drug use (IVDU) was more common in donors with genotype 3a than in those with genotype 1a (p = 0.024), and prior blood transfusion more common in genotype 2b than in 3a (p = 0.012). Chronic active hepatitis with and without cirrhosis was found in 38% of donors infected with genotype 2b as compared to 8% of donors infected with 1a (p = 0.034). Forty percent of donors with genotype 1a had normal ALAT at the time of liver biopsy versus 11% with genotype 3a (p = 0.046). Antibodies to C33c and C22-3 were present in nearly all donors whereas reactivity to C100-3 and 5-1-1 was detected more often in donors with genotypes 1a and 1b as compared to donors with genotypes 2b and 3a. In conclusion, genotype 3a was correlated to IVDU or tattooing as parenteral risk factors for the acquisition of HCV infection, and genotype 2b to prior blood transfusion. Donors with genotypes 1a seemed to have less severe liver disease than those infected with genotypes 2b and 3a.