Viral hepatitis. A population-based study in Rochester, Minn, 1971-1980.

The incidence of acute viral hepatitis among Rochester, Minn, residents 1971-1980 was 28.6 per 100,000 person-years (p-y) (age- and sex-adjusted to the 1980 white population in the United States). The adjusted incidence of hepatitis B (12.9 per 100,000 p-y) was somewhat less than for hepatitis non-B (15.6 per 100,000 p-y). Each type was more frequent among young adults, especially males. The incidence of hepatitis was greater among those employed in the health service industry than among nonmedical employees (53.4 vs 20.0 per 100,000 p-y). Medical employees had nearly a fivefold increased incidence of hepatitis B and a twofold increased incidence of hepatitis non-B. Exposure to known hepatitis cases was common, but other possible causative factors were not frequent. In this midwestern community, the incidence of acute viral hepatitis is substantial, with medical employees at significantly increased risk.

Sodium-lithium countertransport and blood pressure in healthy blood donors.

Studies finding an increased maximal rate of Na-Li countertransport in red blood cells from persons with essential hypertension and their normotensive offspring have raised the possibility that Na-Li countertransport may serve as a marker for the genetic predisposition to hypertension. We studied Na-Li countertransport in 238 randomly selected blood donors representative of the population of Rochester, Minnesota. The mean value (+/- SD) for Na-Li countertransport in units of mmoles of lithium efflux per liter of red blood cells per hour was 0.29 +/- 0.12. The distribution of Na-Li countertransport values among the donors was continuous. An analysis for multimodality, however, detected significant evidence of bimodality with 72% of the population predicted to belong to the lower mode with a mean of 0.24 mmol/L red blood cells per hour and 28% of the population to belong to the upper mode with a mean of 0.42 mmol/L red blood cells per hour. There was a positive association between Na-Li countertransport and blood pressure; after adjustment for weight and age, Na-Li countertransport predicted approximately 3% of the variation in blood pressure. Persons belonging to the upper mode of the Na-Li countertransport distribution may be at increased risk of acquiring elevated blood pressure as they age.

Mixed lymphocyte culture, phytohemagglutinin stimulation, and matching grade: clinical relevance in renal transplantation from living related donors.

Mixed lymphocyte cultures (MLC), including phytohemagglutinin (PHA) stimulation and HLA-A and HLA-B loci typing of donor and recipient, were performed on 70 renal allograft recipients and relevant family members. Graft survival was correlated retrospectively with matchnd PHA response index (PHARI), in order to assess the clinical relevance of each variable singly or jointly. Overall graft survival was significantly associated with SI (log10) (P less than 0.001) and matching grade (P = 0.027). No significant association with either PHARI or II was detected (P greater than 0.10). In addition, the product of the last two indices--the lymphocyte response index (LRI)--was not found to be related to graft survival (P greater than 0.10). Survival of grafts with one-haplotype identity was significantly associated with SI (P = 0.002). Survival in this group was not found to be related to II, PHARI, or LRI, considered either alone or jointly (P greater than 0.10). Grafts with two-allele-identical grafts, whereas PHARI did not differ. SI and matching grade were related significantly to graft survival and appeared to be the most important variables.

Human T-cell leukemia virus type I (HTLV-I) and blood transfusion.

Human T-cell leukemia (or T-lymphotropic) virus type I (HTLV-I) is a human exogenous infectious retrovirus of the family Retroviridae. This virus has been associated with adult T-cell leukemia and endemic myelopathies (tropical spastic paraparesis and HTLV-I associated myelopathy). HTLV-I is transmitted by sexual contact, from mother to child, by intravenous drug abuse, and by blood transfusion. The estimated lifetime risk of developing disease in antibody-positive patients is 1 in 80, and a latency period as long as 20 years can intervene. No case of transfusion-transmitted disease has been reported to date. Currently, no testing of blood donors for HTLV-I is required in the United States, and no such test has been approved by the Food and Drug Administration. Because data on the natural history of this virus may take years to accumulate, it is probably wise to begin excluding anti-HTLV-I-positive units from the blood supply in the United States as soon as a licensed test is available.

Frequency and significance of antibody to hepatitis C virus in severe corticosteroid-treated autoimmune chronic active hepatitis.

To determine the frequency and significance of antibody to hepatitis C virus (anti-HCV) in severe autoimmune chronic active hepatitis, we tested sera from 85 cortico-steroid-treated patients by an enzyme immunoassay. Seropositive patients were assessed for specific antibodies to hepatitis C virus-encoded antigens by recombinant immunoblot assay. The findings in patients with and without anti-HCV were contrasted, and the frequency of seropositivity was compared with that in patients who had other types of chronic liver disease and in normal adults. Only 5 of the 85 patients with autoimmune hepatitis (6%) were seropositive for anti-HCV, and only 2 of these patients were reactive by recombinant immunoblot assay. The frequency of seropositivity in autoimmune hepatitis was not significantly different from that in hepatitis B surface antigen-positive (9%) and cryptogenic (18%) disease, but it was significantly less than that in posttransfusion chronic active hepatitis (6% versus 75%; P less than 0.001). Two patients became seronegative after corticosteroid therapy; both had been nonreactive by recombinant immunoblot assay. Four of the seropositive patients entered remission during corticosteroid therapy, including three whose sera were nonreactive to virus-encoded antigens. We conclude that anti-HCV occurs infrequently in corticosteroid-treated severe autoimmune hepatitis and that antibodies detected by enzyme immunoassay may be nonreactive to hepatitis C virus-encoded antigens. Seropositive patients who are nonreactive by immunoblot assay may still respond to corticosteroid therapy and become seronegative during treatment.

Intraoperative autologous transfusion.

Intraoperative autologous transfusion is a technique that was first used almost 2 centuries ago but that has realized its potential only in the past 5 years. A growing national awareness of transfusion-related morbidity, of the need for alternative blood sources, and of improved methods for red blood cell recovery has led to an increased frequency of use of autologous transfusion. Most hospital programs use semicontinuous flow centrifugation or canister technology for the intraoperative salvage and reinfusion of shed blood. This technique is particularly valuable for cardiovascular surgical procedures but has been useful in many other types of surgical procedures as well. Deleterious effects formerly attributed to this technique have been eliminated by methodologic improvements. Concerns about use of autologous transfusion in patients who have an infection or a malignant lesion persist. Most hematologic aberrations are related to massive transfusions and should not be considered a contraindication to the general use of autologous blood.

Frequency and significance of antibody to hepatitis C virus in severe corticosteroid-treated cryptogenic chronic active hepatitis.

To determine the frequency and significance of antibody to hepatitis C virus (anti-HCV) in severe cryptogenic chronic active hepatitis (CAH), we tested sera from 17 corticosteroid-treated patients by an enzyme immunoassay. Specificity of the antibodies to HCV-encoded antigens was assessed by recombinant immunoblot assay. The findings in patients with and without anti-HCV were contrasted, and the frequency of seropositivity was compared with that in patients who had other types of chronic liver disease and in normal adults. Only three patients (18%) with severe cryptogenic CAH had anti-HCV. Sera from two of these patients were reactive by recombinant immunoblot assay; the other sample produced an indeterminate reaction. The frequency of seropositivity in patients with cryptogenic disease was not statistically different from that in patients with autoimmune CAH (6%), hepatitis B surface antigen-positive CAH (9%), or alcoholic liver disease (0%), but it was significantly less than in those with posttransfusion CAH (18% versus 75%; P less than 0.01). Seropositive patients tended to have lower serum aspartate aminotransferase, gamma-globulin, and bilirubin levels than seronegative counterparts, and they did not have histologic features of confluent necrosis at initial assessment. Two of the three seropositive patients, both of whom had been reactive by recombinant immunoblot assay, entered remission during therapy, and one, with an indeterminate reaction, died of liver failure. We conclude that anti-HCV occurs infrequently in severe corticosteroid-treated cryptogenic CAH. Seropositive patients may have less severe inflammatory activity than seronegative counterparts. Cryptogenic disease may improve during corticosteroid treatment, a result suggesting an underlying immunologic disorder in some patients.

Autologous blood transfusion.

Autologous blood transfusion is a procedure in which blood is removed from a donor and returned to his circulation at some later time. Autologous transfusion can be performed in three ways: (1) preoperative blood collection, storage, and retransfusion during surgery; (2) immediate preoperative phlebotomy with subsequent artificial hemodilution and later return of the phlebotomized blood; and (3) intraoperative blood salvage and retransfusion. All three methods of autologous transfusion offer a potentially superior method of blood transfusion which eliminates many of the problems and complications associated with the banking and administration of homologous donor blood.

Blood transfusion for the patient who is difficult to transfuse.

There are two types of patients who are difficult to transfuse because of the presence of red cell antibodies, those patients who have an antibody reactive against an antigen of high incidence and those who have multiple antibodies. Possible sources of blood for the patient who has an antibody reactive against a high-incidence red cell antigen include the patient's family, rare donors lacking the high-incidence antigen, and self-donation. Possible sources of blood for those who have multiple antibodies are limited to rare donors lacking the appropriate combination of antigens or to self-donation.

Hemolytic transfusion reaction. Recent experience in a large blood bank.

Data on 47 cases of hemolytic transfusion reactions are presented along with a review of the literature. Human error and limitations of current techniques of compatibility testing remain the major causative factors of hemolytic transfusion reactions.

Intraoperative autologous transfusion: its role in orthotopic liver transplantation.

In our orthotopic liver transplantation program, intraoperative autologous transfusion was used in 89 of the first 100 procedures. In these 89 cases, intraoperative autologous transfusion provided a mean of 6.2 erythrocyte units per case or 32% of the total intraoperative erythrocyte requirements. The maximal number of erythrocyte units administered to any patient was 36.6 units (and 51% of the erythrocyte requirements). The most rapid rate of reinfusion of intraoperatively salvaged blood (11.8 units/h) occurred during reperfusion. No coagulopathy, infectious sequelae, or other complications were attributable to intraoperative autologous transfusion. In patients with large volumes of blood loss, intraoperative autologous transfusion is cost-effective, apart from the consideration of its medical benefits. Use of intraoperative autologous transfusion in liver transplantation resulted in conservation of erythrocytes and reduction in exposure to homologous blood and blood components.

Chronic granulomatous disease and the Mcleod phenotype. Successful treatment of infection with granulocyte transfusions resulting in subsequent hemolytic transfusion reaction.

A young man with X-linked chronic granulomatous disease of childhood, who is of the rare McLeod phenotype with antibodies in his serum shown to be hemolytic and reactive against all red cells with normal expressions of the Kell antigens, developed a severe Nocardia pneumonia with abscess formation and was subsequently treated successfully with granulocyte transfusions in spite of the presence of anti-KX in the patient's serum. The anti-KX did not appear to alter significantly the effectiveness of the transfused granulocytes; it did, however, cause a mild hemolytic transfusion reaction. The patient made a remarkable recovery from this episode and his condition has progressed to a state satisfactory enough for him to donate his own blood for storage and possible use in the future.

Plasmaperfusion for the treatment of intractable pruritus of cholestasis.

A patient with primary biliary cirrhosis and intractable pruritus was treated with plasmaperfusion of charcoal-coated glass beads on two occasions. The procedures were well tolerated and resulted in the removal of about 70% (494 mumol) of the estimated chenic acid pool. There was, in addition, pronounced amelioration of the pruritus which enabled the patient to sleep through the night without awakening because of itching. The pruritus, however, did not disappear and gradually returned to its preperfusion intensity by the end of the third week after perfusion.

HLA antigens in patients with juvenile diabetes and their first-degree relatives.

The relationship between HLA antigens and juvenile-onset diabetes mellitus was examined. Tissue typing for HLA antigens was carried out in 77 control subjects and in 133 individuals from 29 families, each of which contained one or more patients with juvenile-onset diabetes. A significant increase in the frequency of B18 antigen was found in the juvenile-onset index cases. In these index cases, the frequency of HLA antigens B8 and B15 was increased and the frequency of B7 and B12 was decreased, but these findings were not significantly different from those in the control subjects. Two examples of recombinations were noted among the 29 families, and in both instances the recombinations were present in the index case. In this selected population of diabetic patients and their first-degree relatives, there were three siblings (6%) who had juvenile-onset diabetes mellitus. This frequency of diabetes in siblings is much more than would be expected in individuals of the same age group. Two nondiabetic siblings had haplotypes identical to those of a diabetic sibling. These nondiabetic siblings may represent prediabetic individuals. The most frequent haplotype noted in diabetic patients and their first-degree relatives was A1, B8, which was present in approximately 25% of the index cases and first-degree relatives.

Prognostic and therapeutic implications of extreme serum aminotransferase elevation in chronic active hepatitis.

Extreme elevation of the serum aspartate aminotransferase level typically suggests acute hepatocellular necrosis and may militate against the diagnosis of chronic active hepatitis. However, we found that 26 of 160 patients (16%) with chronic active hepatitis had aminotransferase elevations of more than 1,000 IU/liter. These patients were younger and more often jaundiced than the others, but they exhibited signs of chronic liver disease as often. In only 2 of 26 patients with extreme aminotransferase abnormality were features of chronic disease absent. Patients with extreme enzyme elevation had histologic findings of confluent necrosis (P greater than 0.005) and features associated with acute viral infection (P greater than 0.005) more often than others, but they as often had cirrhosis on biopsy specimens. Virologic markers did not distinguish the patients or correlate with viral features in liver tissue. Corticosteroids improved immediate survival (P greater than 0.005) and the likelihood of remission (P greater than 0.005). Although chronic active hepatitis may present with extreme aminotransferase elevation and histologic features associated with acute viral infection, ancillary features of chronic disease facilitate the correct diagnosis and the initiation of appropriate therapy.

Frequency and significance of immunoglobulin M antibody to hepatitis B core antigen in corticosteroid-treated severe chronic active hepatitis B.

To assess the frequency and significance of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc) in corticosteroid-treated severe chronic active hepatitis B, we tested 96 serum samples from 16 patients who were seropositive for hepatitis B surface antigen (HBsAg) (group 1) and 8 HBsAg-negative, anti-HBc-positive patients (group 2) by enzyme-linked immunoassay. Samples obtained in the presence and absence of disease activity before, during, and after long-term corticosteroid therapy (mean duration, 42 +/- 7 months) were evaluated. Seropositivity for IgM antibody was demonstrated in 12 group 1 patients, including 9 tested before corticosteroid therapy; no group 2 patients were seropositive. Seropositivity was more common in serum samples obtained during active than during inactive disease (51% versus 22%; P less than 0.05) and more frequent in serum samples that contained hepatitis B e antigen (46% versus 11%; P less than 0.02) and hepatitis B virus deoxyribonucleic acid (50% versus 24%; P less than 0.05) than in those without these markers. In some patients, seropositivity persisted or recurred intermittently during corticosteroid therapy for up to 57 months. We conclude that seropositivity for IgM antibody can be demonstrated frequently by enzyme-linked immunoassay in corticosteroid-treated patients with severe disease. Seropositivity reflects active virus replication, and it is commonly associated with inflammatory activity. The duration of seropositivity may be protracted during long-term corticosteroid therapy.

Effect of blood conservation efforts in cardiac operations at the Mayo Clinic.

In a retrospective study of 388 patients who had undergone cardiac operations at our institution during two time periods-before (1982) and after (1984) introduction of autologous transfusion-we analyzed the effect of blood conservation efforts and autologous transfusion on blood usage, postoperative complications, and duration of hospitalization. Cell salvage techniques resulted in a significant reduction (P less than 0.0001) in use of not only homologous blood (from a mean of 9.6 units per patient in 1982 to 3.2 units in 1984) but also fresh-frozen plasma and platelet concentrates. We found no significant difference in morbidity or mortality for the two study periods. Although the mean duration of hospitalization decreased from 11.7 days in 1982 to 9.6 days in 1984, this change was probably related to factors other than the introduction of blood conservation efforts. Thus, techniques used to decrease the amount of blood replacement needed for cardiac surgical procedures are beneficial.

A blood bank consultation service: principles and practice.

In the blood bank setting, a close relationship with both clinicians and patients is essential for good medical practice. In July 1982, the Mayo Clinic Blood Bank and Transfusion Services formally organized a consultation service with daily visits to patients of mutual interest to blood bank consultants and clinicians for practice and education. Detailed diaries of this activity were maintained for 12 months, during which time 802 impatient visits were recorded. The most frequent reasons for consultations were clarification or amplification of the clinical history (34.0%), evaluation of transfusion reactions (27.2%), and assessment of serologic problems (18.2%). These consultations resulted in diagnostic, management, and therapeutic recommendations for a wide variety of medical problems. Of the 802 consultations, 23% were conducted at the direct request of clinicians. We believe that a blood bank consultation service is feasible, is enlightening for the blood bank and clinicians, and contributes to patient care.

The first 100 liver transplantations at the Mayo Clinic.

Between March 1985 and June 1987, the first 100 liver transplantations at the Mayo Clinic were performed in 83 patients (primarily adults). The most frequent diagnoses were chronic active hepatitis (in 24 patients), primary sclerosing cholangitis (in 22), and primary biliary cirrhosis (in 20). The median operating time was 406 minutes, and the median usage of erythrocytes was 13.2 units. A venovenous bypass was used in all patients older than 10 years of age. Hepatic artery thrombosis occurred in 10% of the 100 transplants. A choledochocholedochostomy was done in 58 patients and a choledochojejunostomy in 25 patients. Revision of the biliary anastomosis was necessary in 9 of the 83 patients (11%). Rejection, diagnosed by clinical and histologic criteria, occurred in 50 patients (60%) and was treated with a corticosteroid bolus, followed by OKT3 (monoclonal antibody) treatment if necessary. Selective bowel decontamination helped prevent infections; only 16 bacteremias occurred, 1 of which was caused by a gram-negative organism. Fungal infections were rare. Cytomegalovirus infection occurred in 47 patients (57%). Of the 83 patients, 16 required retransplantation, in 11 of whom graft rejection had occurred. One- and 2-year patient survival was 83% and 70%, respectively. Although problems still remain, liver transplantation is a reasonable option for patients with end-stage liver disease.

Failure of interferon to prevent recurrent hepatitis B infection in hepatic allograft.

Chronic liver disease associated with hepatitis B virus infection is both common and serious; no satisfactory treatment currently exists. Orthotopic liver transplantation is an option for patients with end-stage liver disease associated with hepatitis B virus infection despite the risk of allograft reinfection. Passive immunoprophylaxis has been attempted perioperatively to prevent graft infection but has not been beneficial. Some patients with chronic type B hepatitis have benefited clinically from antiviral therapy and, in particular, interferon, but its use has not previously been reported as an approach to prevent allograft infection. We administered recombinant leukocyte A interferon perioperatively to a patient who underwent liver transplantation for type B chronic active hepatitis and cirrhosis. Circulating hepatitis B virus DNA was found postoperatively while the patient was receiving interferon, and stainable viral antigen subsequently reappeared in the transplanted liver. Thus, the drug failed to prevent viral replication and allograft infection. Thus far, no evidence of progression of the chronic hepatitis has been noted.