Pasteurized, monoclonal antibody factor VIII concentrate: establishing a new standard for purity and viral safety of plasma-derived concentrates.

A factor VIII concentrate (Monoclate-P) manufactured using a combination of pasteurization and immunoaffinity chromatography has been chosen to compare and contrast manufacturing aspects of plasma-derived factor VIII concentrates. Pasteurization is a virucidal method with a long safety record in clinical practice, while immuno-affinity chromatography selectively isolates and purifies the procoagulant protein of factor VIII, and partitions potential viral contaminants and nonessential proteins to the unbound fraction. The complete Monoclate-P production process reduces human immunodeficiency virus by > or = 10.5 log10, Sindbis (a model for hepatitis C virus) by > or = 6.5 log10, and murine encephalomyocarditis virus (a non-enveloped model virus) by 7.1 log10. The viral safety of Monoclate-P has been further demonstrated in clinical studies in patients not previously treated with blood or plasma-derived products. Additionally, the manufacture of Monoclate-P includes careful donor screening and plasma testing for antibodies to syphilis and human immunodeficiency, hepatitis B, and hepatitis C viruses to enhance source plasma safety. Combined with donor selection and plasma testing, multiple viral reduction steps effectively eliminate both lipid-enveloped viruses (e.g. human immunodeficiency, hepatitis B and C) and non-lipid-enveloped viruses (e.g. hepatitis A). In addition, polymerase chain reaction-based nucleic acid detection tests for hepatitis B and C viruses and for human immunodeficiency virus-1 have been introduced as part of an investigational new drug mechanism.     

Antibody Response to Hepatitis C Virus Infection after Liver Transplantation

Objective: To determine whether liver transplantation and the subsequent immunosuppression affect the antibody response to hepatitis C virus (HCV) infection. Methods: Sera from 46 patients were compared before and after liver transplantation for markers of HCV infection. Serum HCV RNA was determined by polymerase chain reaction (PCR). Anti-HCV antibody was determined by first- and second-generation immunoas-says as well as a quantitative assay of the titer of anti-HCV core antibody. Results: Among individuals who acquired hepatitis C infection in association with liver transplantation, only 15% (3/12) developed antibody to the core antigen and only 25% (3/12) reacted to any antigen present on the second-generation recombinant immunoblot assay after a mean follow-up period of 18 months. Thirty-eight percent (5/13) were positive, by the second-generation enzyme immunoassay (EIA-2). Whereas 94% (16/17) of the individuals who had detectable anti-HCV core antibodies pretransplant continued to have such antibodies after transplant, the titer of these antibodies declined an average of 4-fold. No significant change was seen in the antibody titer toward rotavirus, a common viral pathogen. Patients who acquired HCV infection or in whom the allograft became reinfected had a significantly increased incidence of posttransplant hepatitis (61% vs . 33%, respectively). Conclusions: Liver transplantation and posttransplant immunosuppression lead to an attenuated antibody response to hepatitis C viral infection. Currently available assays for anti-HCV antibodies may be unreliable in the posttransplant setting.     

Antiplatelet antibodies in patients with chronic viral hepatitis receiving interferon-alpha

BACKGROUND/AIMS: The aim of this study was to investigate the possible role of interferon-alpha in the development of antiplatelet IgG antibodies in patients with chronic viral hepatitis B or C. METHODOLOGY: Ninety-one consecutive patients with chronic viral hepatitis (51 with chronic hepatitis B and 40 with chronic hepatitis C) were investigated for the presence of antiplatelet IgG antibodies in their serum immediately prior to IFN-alpha therapy and after six months of therapy. The method used was the solid phase red cell adherence test (Immucor, Norcross, USA), which is a sensitive tracer of antiplatelet antibodies. Some of the results were confirmed using an indirect immunofluorescence test for the detection of antiplatelet antibodies RESULTS: Overall, we found that antiplatelet antibodies were present in 37.54% (19/51) of patients with chronic hepatitis B before IFN-alpha therapy and in 35.29% (18/51) after therapy. Moreover, antiplatelet antibodies were found in 20% (8/40) of patients with chronic hepatitis C before and after IFN-alpha therapy. CONCLUSIONS: Therapy with IFN-alpha did not induce antiplatelet antibodies in patients with chronic viral hepatitis B or C. Thrombocytopenia observed during IFN-alpha therapy in our study was not due to the development of antiplatelet antibodies.     

Variation in inhibitor reactivity in acquired haemophilia A with different concentrates

Acquired haemophilia A due to the development of auto-antibodies directed against factor VIII (FVIII) is a rare disorder that may result in serious haemorrhagic episodes. Although in many cases no associated underlying disorders are apparent, the condition has been reported in association with autoimmune disorders, haematological malignancies, treatment with certain drugs and pregnancy. The reaction kinetics of auto-antibodies to FVIII differ from those observed with allo-antibodies in congenital haemophilia. Previous studies in congenital haemophilia have raised the possibility that inhibitory antibodies vary in their reactivity with the factor VIII molecules in different concentrates used for treatment. However, the interaction of FVIII in concentrates and inhibitors in acquired haemophilia has never been previously studied. In this study, the effect of different FVIII concentrates was studied on neutralization in vitro by performing inhibitor titres using the New Oxford inhibitor assay method. The inhibitor titre in eight patients with acquired haemophilia A was assayed against five commercially available FVIII concentrates of varying purity. The intermediate purity concentrate 8Y and the high purity concentrate that contains normal amounts of von Willebrand's Factor (vWF) (Alphanate) gave lower titres than the high purity concentrates with low (Monoclate-P) or no (Kogenate) von Willebrand content. All but one antibody had very low reactivity with porcine FVIII. Further work will be required to establish whether concentrates manifesting a low level of in vitro reactivity with the inhibitor have a better haemostatic effect in vivo.     

Long-term surveillance of haematopoietic stem cell recipients with resolved hepatitis B: high risk of viral reactivation even in a recipient with a vaccinated donor

Reactivation of resolved hepatitis B virus (HBV) infection is increasingly recognized in patients with severe immunosuppression. We monitored seven patients with pretransplant antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc) for HBV reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Reverse seroconversion (from anti-HBs to HBsAg) was observed in six recipients occurring 12, 14, 16, 22, 31 and 39 months after allo-HSCT, respectively. The only patient without HBV reactivation had the highest pretransplant anti-HBs titre and died after the shortest follow-up period (25 months). A novel HBV surface mutant (D144G/G145E) was isolated from one recipient of stem cells from a donor vaccinated against HBV. Another surface mutant (P142L/G145R) was detected in a recipient from a non-immune donor. Serum ALT elevation was measured in only two of the six patients with viral reactivation, followed by spontaneous clearance of HBsAg in one of them. Antiviral treatment reduced viral load in five patients, but the emergence of YMDD motif polymerase mutations resulted in lamivudine resistance in two patients. In conclusion, the risk of reactivation of a resolved HBV infection is close to 100% in allogeneic stem cell recipients and vaccination of the donor does not always warrant reliable protection.     

Recombinant interferon-α therapy for acute hepatitis B: a randomized, double-blind, placebo-controlled trial

In spite of the availability of hepatitis B vaccine, acute hepatitis B continues to be a worldwide problem for which no specific therapy is available. We investigated the safety and the effectiveness of recombinant interferon-α2b (rIFN-α2b) in the treatment of acute hepatitis B by determining overall severity and duration of symptoms, time required to clear viral antigens and hepatitis B virus (HBV) DNA, and titre of antibodies to hepatitis B surface antigen (HBsAb), 24 weeks after the onset of therapy. One hundred patients were randomly assigned to treatment with either 3 million units (MU) ( n =34) or 10MU ( n =33) rIFN-α2b or to placebo ( n =33), three times weekly for 3 weeks. Follow-up was for 24 weeks. A significantly shorter duration of the symptoms and signs of acute hepatitis was observed in patients who received 3MU rIFN-α2b compared with those who received 10MU rIFN-α2b or placebo. Twenty-one weeks post-therapy, patients treated with 10MU rIFN-α2b showed a significantly higher geometric mean HBsAb titre than those treated with placebo (85.1 vs 35.5IUl^–1, P <0.05). rIFN-α2b administration was well tolerated even in jaundiced patients. No serious side-effects were observed necessitating reduction in dose or discontinuation of the drug. The effect of rIFN-α2b on transition of HBV infection to chronicity could not be evaluated in this trial because such an unfavourable course was not seen in any of the treated or the control patients. In conclusion, rIFN-α2b was safe in acute hepatitis B, and at low dose was found to ameliorate symptoms and to shorten significantly the duration of illness.     

Screening for viral markers in volunteer and replacement blood donors in West Africa

BACKGROUND AND OBJECTIVES: West Africa is a highly endemic area for viral infections. The prevalence of five viral markers was determined in Ghanaian blood donors. MATERIALS AND METHODS: Replacement and volunteer blood donors were screened using enzyme immunoassays (EIAs) for hepatitis B surface antigen (HBsAg), human immunodeficiency virus antibodies (anti-HIV), HIV p24 antigen, human T-cell lymphocytotrophic virus-I and -II antibodies (anti-HTLV-I/II) and hepatitis C virus antibodies (anti-HCV). RESULTS: HBsAg was present at an equally high frequency (15%) in young volunteer (median age 18 years) and older replacement (median age 33 years) blood donors. In contrast, the prevalence of anti-HIV and anti-HCV was significantly higher in replacement blood donors (2.4 and 0.3%, respectively, P < 0.001). HCV RNA was detected in 74 or 55% of seropositive donors, depending on the confirmatory criteria used. No p24 antigen-positive/anti-HIV-negative donations were found. The prevalence of HTLV-I/II was generally low (0.5%). CONCLUSION: All blood donations should be screened for hepatitis B virus (HBV), HIV and HCV markers.     

Interferon treatment in hepatitis B surface antigen-positive hepatitis B e antibody-positive chronic hepatitis B: role of hepatitis B core antibody IgM titre in patient selection and treatment monitoring

Chronic hepatitis B infection with the hepatitis B e antigen (HBeAg)-negative variant is associated with a severe clinical course and a low response rate to interferon (IFN). In an attempt to improve the chances of sustained response to interferon we designed a pilot study, using titres of IgM antibodies to hepatitis B core antigen (HBcAb IgM) to guide treatment initiation. Eighteen adults who were HBeAg-negative with biopsy-proven chronic active hepatitis (seven with cirrhosis) entered the study. They were followed-up bimonthly with routine liver function tests, and HBcAb IgM titres were also determined. Treatment (lymphoblastoid IFN 5 million units (MU) m^–2 three times weekly for 6 months) was started when the HBcAb IgM titre was increasing. Fifteen (83.3%) patients had normal alanine aminotransferase (ALT) levels and undetectable HBV DNA at the end of treatment. HBcAb IgM decreased in all responders. We observed a relapse in four patients (three with cirrhosis), in the first year after treatment, with an increase in ALT, HBV DNA and titre of HBcAb IgM. Eleven patients (61.1%) had a sustained response and eight of these 11 patients were followed-up for more than 18 months; two responders cleared hepatitis B surface antigen (HBsAg). Hence, the rate of sustained response to IFN in HBeAb-positive patients with chronic hepatitis is improved if treatment is started when HBcAb IgM levels are increasing.     

Hepatitis Virus Infections in Spouses of Blood Donors

An important purpose of the medical history in selecting individuals for blood donation is to protect the recipient against the transmission of viral diseases. Over many years hepatitis was the main cause of transfusion-associated chronic disease and death. Three steps led to a large reduction of the frequency of transfusion-associated hepatitis: Systematic exclusion of donors reporting defined risk factors and the introduction of tests for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (HCV) [ 1 ]. However, despite the development of sensitive and specific screening tests there is no doubt that a detailed medical history is the basis of all progress in providing safe blood products because any screening test is tainted with the problem of the window period between infection and seroconversion.     

Clinical Evaluation of a Recombinant Factor VIII Preparation (Kogenate) in Previously Untreated Patients with Hemophilia A

The safety and efficacy of a recombinant factor VIII (rFVIII) preparation (Kogenate) for the treatment of bleeding episodes was studied in previously untreated patients (PUPs) with severe, moderate, and mild hemophilia A. Patient peripheral blood samples taken at baseline and at 3, 6, 9, 12, 18, and 24 months after the first infusion were evaluated for FVIII inhibitor antibodies by the Bethesda assay, for antibodies formed against trace proteins derived from the rFVIII production process, and for general changes in laboratory test results. Samples for general laboratory testing were also drawn every 6 months after the first 24 months. Hemostatic efficacy was assessed by physicians, and adverse events were recorded throughout the study period. Forty-three PUPs (30 with FVIII:C <1%; 10 with FVIII:C 1%-5%; and 3 with FVIII:C >5%) aged 3 months to 32 years were enrolled at 33 centers in Japan. Patients were studied for a mean of 51 months (range, 11-80 months), and the mean exposure time was 83 days (range, 2-571 days). The incidence of occurrence of FVIII inhibitors was 34.9% (high responders [> or = 10 Bethesda U/mL], 11.6%; low responders [0.5-<10 Bethesda U/mL], 23.3%). The median cumulative exposure time of inhibitor detection was 12 days, indicating inhibitor development at an early stage after the start of infusion of this preparation. Hemostasis was achieved with a single dose of Kogenate in 94.8% of the 951 bleeding episodes recorded in the study. Transient increases in antibodies against baby hamster kidney proteins and antimouse immunoglobulin G were observed in 14.0% and 18.6% of patients, respectively. Anti-rFVIII seroconversion was observed in 18.6% of patients and only in patients with inhibitor antibodies. Antibody responses to trace proteins were not correlated with drug-related adverse events with the exception of FVIII activity inhibition in PUPs with anti-rFVIII seroconversion. These data indicate that Kogenate is safe and effective for the treatment of bleeding in PUPs with hemophilia A.     

The impact of hepatitis screening on diagnosis and treatment in rheumatoid arthritis

Identification of patients with exposure to viral hepatitis is an important part of the care of patients with inflammatory arthritis. This study was conducted to assess the extent of hepatitis B and C screening, and the prevalence of viral hepatitis in a cohort of patients with established rheumatoid arthritis (RA). The medical records of 100 consecutive RA patients were retrospectively analysed for screening of hepatitis B surface antigen, surface antibody and core antibody and hepatitis C antibody. A teaching session was then conducted with the rheumatology team, emphasising the rationale for viral hepatitis testing. We then prospectively analysed 100 more RA patients to see if hepatitis screening improved. In the initial 100 patients (21 % male, mean age 65 years), 85 % were taking methotrexate and 22 % biologic treatments. A complete hepatitis screen was present in 8 %, while 12 % had hepatitis B core antibody checked and 53 % had been tested for hepatitis C. The second cohort of patients was similar to the first in terms of demographics and treatment. A complete hepatitis screen was available in 63 %, while 65 % had hepatitis B core antibody checked and 81 % had been tested for hepatitis C. In total, we identified 4 new cases of positive hepatitis B core antibody, 11 cases of positive hepatitis B surface antibody and 1 case of positive hepatitis C antibody. Even in populations where hepatitis B or C is non-endemic, screening will reveal new cases. Educational initiatives are helpful in teaching staff to screen patients.     

Postoperative paraneoplastic factor VIII auto‐antibodies in patients with solid tumours

Summary. Paraneoplastic FVIII antibodies may occur concurrent with the diagnosis or at various times after diagnosis and treatment of cancer. Between 2002 and 2009, we observed two patients with acquired haemophilia A due to an FVIII auto‐antibody, which appeared 4 and 5 months after uncomplicated cancer surgery. We aimed to evaluate if such an association of cancer surgery and FVIII antibody formation has been observed previously. We retrieved all published case reports of cancer‐associated FVIII auto‐antibodies from PubMed for the period 1950–2010. The search in the literature revealed 13 patients in whom a FVIII inhibitor developed after uncomplicated surgery for cancer and a bleeding‐free time interval of up to 6 months; 11/15 patients had abdominal cancers (five colon cancer, four pancreatic cancer, gastric cancer and choledochus carcinoma one each). The median time period between surgery and antibody detection was 3 months (1 week–6 months). In most cases, the antibody titre was low (median: 14 BU mL^?1, range: 1.7–64 BU mL^?1). Immunosuppressive treatment was successful in most of the cases – nine of the treated patients reached a sustained CR of the antibody after a median time of 3 months. Postoperative paraneoplastic FVIII inhibitors may be regarded as a special, not yet recognized subgroup of acquired FVIII antibodies. They share some characteristics with postpartum FVIII inhibitors with regard to the latency period between the triggering event and the appearance of the antibody, and between the usually low antibody titres and their good response to immunosuppressive treatment.     

Interferon treatment of chronic hepatitis C in patients cured of pediatric malignancies

BACKGROUND AND OBJECTIVE: Chronic hepatitis C was a frequent complication in patients treated for malignancy until the introduction of anti-HCV screening tests for blood donors. The association between chronic hepatitis C and progression to cirrhosis and hepatocellular carcinoma has been reported in about 20% and 5% of patients, respectively, within 20-30 years of infection. In adult patients, interferon has proved to be effective in decreasing the abnormal values of transaminases and the level of HCV viremia. Our purpose was to assess efficacy of and tolerance to interferon in a group of young patients who had acquired HCV infection during a period of chemotherapy. DESIGN AND METHODS: Interferon-a (IFN) was administered to 26 adolescents and young adults (13 males, age range 17-36 years; median age 24) with chronic hepatitis C, including 4 with hepatitis B virus co-infection, who had been treated for leukemia or solid tumor 5 to 19 years before joining this trial. Patients were treated with natural IFN alpha at a dose of 4 MU/m(2) thrice weekly for 12 months and followed up for another 6 months thereafter. RESULTS: Nine patients stopped treatment during the first 6 months because of side effects (2 cases) or lack of response. At the end of the trial, 8 (31%) cases had responded, with alanine amino-transferase normalization and clearance of hepatitis C virus (HCV) RNA. A sustained response was only documented in 15% of cases, however, irrespective of any hepatitis B virus co-infection. The 2 patients with HCV genotype 2 were both responders, whereas only 8% of those with genotype 1 responded. INTERPRETATION AND CONCLUSIONS: These data show that the efficacy of IFN in this series of young patients is similar to that reported for otherwise healthy adults with hepatitis C. Patients with genotype 2 are strong candidates for IFN treatment while other therapeutic strategies should be designed for patients with HCV genotype 1.     

Predictive Value of Screening Tests for Persistent Hepatitis C Virus Infection Evidenced by Viraemia: Japanese Experience

In November 1989, Japanese Red Cross Blood Centres started screening for heaptitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the C100-3 viral peptide as the first such nationwide programme in the world. Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61–80%, but this was not as complete a success as our programme to prevent post-transfusion hepatitis B by screening for high titer hepatitis B core antibody, which we began in the same period. In order to acquire more effective control of PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa (Ortho2, Abbott2)and second-generation antigen agglutination (PA, PHA) tests have been employed. Among 16,500 donors in 11 blood centers, 365 were serologically positive by at least one of these tests. Among these, HCV RNA was detected in 138 units and the remaining 227 were HCV RNA negatives. The effectiveness of these serological tests to detect HCV RNA-positive status were analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests were highly effective to predict HCV viraemia among blood donors. Also, these tests can easily determine antibody titre. By either PHA or PA, all units with ≧2¹² agglutination titre (120 and 122 units) were HCV RNA positive and all agglutination-positive units with serum alanine aminotransferase level higher than 35 Karmen units were HCV RNA positive. These results have formed the basis for implementing a more effective screening for HCV viraemia in blood donors, where effectiveness is defined as enhancing the protection of patients from post-transfusion hepatitis C and providing higher quality information to achieve more effective donor counselling.     

Serological profile of tissue autoantibodies during acute and chronic delta hepatitis

In order to assess the serological profile in relation to other serological and histological markers of hepatitis delta virus (HDV) infection we have investigated the presence of autoantibodies during acute and chronic delta infection in 353 serum samples from different patients with acute and chronic hepatitis and autoimmune diseases. Basal cell layer antibodies (BCLA) were found in 58% acute hepatitis B, in 73% chronic hepatitis D and in 4% primary biliary cirrhosis. Stellate thymic epithelial cell antibodies (SECA) were detected in 40% acute D hepatitis and in 49% chronic D hepatitis. No tissue autoantibodies were detected in 50 acute B hepatitis, 35 autoimmune chronic liver diseases, 24 connective tissue diseases or 25 controls. In addition, two previously unreported specificities of anti-thymic antibodies reacting with reticular (TRA) and perithymocytic cells (PTA) were identified in 33% and 9% acute D hepatitis, respectively, and in 13% and 6% chronic D hepatitis cases. Among patients with acute HBV-HDV coinfection these antibodies were detected transiently (less than 4 weeks) and at low titer, whereas in those with chronic infection autoantibodies levels tend to be high and persistent throughout the follow-up. Among patients with chronic HDV infection no correlation was found between the presence of tissue autoantibodies and hepatic delta antigen expression and serum HDV-RNA which suggest that autoimmune phenomena observed during chronic delta infection are not related to the level of viral replication.     

Cofactor dependence and isotype distribution of anticardiolipin antibodies in viral infections

BACKGROUND: Antibodies to cardiolipin (aCLs) are often detected in patients with autoimmune disorders or infectious diseases. OBJECTIVE: To investigate the distribution of aCL isotypes and requirement of protein cofactor in viral infections in order to establish the importance, if any, of these antibodies in these infectious diseases. PATIENTS AND METHODS: The isotype distribution of aCLs in the sera from 160 patients with infection caused by HIV-1 (n=40), hepatitis A virus (n=40), hepatitis B virus (n=40), or hepatitis C virus (n=40) was studied by standardised enzyme linked immunosorbent assay (ELISA) in the presence and absence of protein cofactor (mainly beta2-glycoprotein I). Serum samples from healthy volunteers and patients with syphilis and antiphospholipid syndrome were also included and served as negative and positive control groups respectively. RESULTS: The prevalence of one or more aCL isotypes in serum of patients with HIV-1, hepatitis A virus, hepatitis B virus, or hepatitis C virus infection was 47%, 92%, 42%, and 17% respectively (principally IgM and/or IgA). Most of these antibodies were mainly cofactor independent. CONCLUSIONS: The presence of aCLs in viral infections is principally cofactor independent, suggesting that cofactor dependence of the aCLs should be assessed to distinguish subjects most likely to suffer from clinical symptoms observed in the presence of these antibodies.     

Acute sporadic viral hepatitis in Ethiopia: causes, risk factors, and effects on pregnancy.

One hundred and ten consecutive cases of acute sporadic hepatitis among Ethiopian patients were studied to define viral causes, identify risk factors, and analyze demographic and clinical data. IgM antibodies to hepatitis A virus were found in nine patients (8%), and hepatitis B surface antigen and IgM antibodies to hepatitis B core antigen were found in 22 (20%); these findings were considered evidence of acute hepatitis A and hepatitis B, respectively. Sera from the remaining 79 patients were tested for antibodies to hepatitis E virus by a blocking fluorescent antibody test. Thirty-six (33%) of these patients were seropositive, as compared to 4 (7%) of 59 healthy control subjects; for 43 patients (39%), the cause of the acute sporadic hepatitis was unidentified. Twenty-one (19%) of the patients had antibodies to hepatitis C virus, as determined by ELISA. Demographic, biochemical, and clinical data (except in regard to sequelae) were comparable for the different types of infections. The study subjects included 32 pregnant women, 19 (59%) of whom had hepatitis E virus infection; these infections caused death in eight of the women (mostly in the third trimester) and 10 fetal complications. Thus, hepatitis E virus is a common cause of acute sporadic viral hepatitis in Ethiopian patients, and its occurrence during pregnancy is associated with high maternal and fetal morbidity and mortality.     

Composition of inflammatory infiltrate and its correlation with HBV/HCV antigen expression

AIM： To study the composition of liver inflammatory infiltrate in biopsy material from patients chronically infected with hepatotropic viruses and to evaluate the correlation of inflammatory infiltrate with hepatitis B virus （HBV） and hepatitis C virus （HCV） viral antigen expression in chronic B and C hepatitis.
METHODS： The phenotype of inflammatory cells was evaluated by the EnVision system, using a panel of monoclonal antibodies. HBV and HCV antigens were detected with the use of monoclonal anti-HBs, polyclonal anti-HBc and anti-HCV antibodies, respectively. RESULTS： The cellular composition of liver inflammatory infiltrate was similar in the patients with B and C hepatitis： ～50%-60% of cells were T helper lymphocytes. Approximately 25% were T cytotoxic lymphocytes; B lymphocytes comprised 15% of inflammatory infiltrate; other cells, including NK, totalled 10%. Expression of HLA antigens paralleled inflammatory activity. Portal lymphadenoplasia was found more often in hepatitis C （54.5%） than in hepatitis B （30.6%）. Expression of HB-cAg was found more often in chronic B hepatitis of moderate or severe activity. Overall inflammatory activity in HBV-infected cases did not correlate with the intensity of HBsAg expression in hepatocytes. Inflammatory infiltrates accompanied the focal expression of HCV antigens. A direct correlation between antigen expression and inflammatory reaction in situ was noted more often in hepatitis C than B.
CONCLUSION： Irrespective of the etiology and activity of hepatitis, components of the inflammatory infiltrate in liver were similar. Overall inflammatory activity did not correlate with the expression of HBsAg and HCVAg; HBcAg expression, however, accompanied chronic hepatitis 8 of moderate and severe activity.