Cases Of Transfusion-associated Hepatitis Research Articles

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.

Commentary

Using a protocol of preoperative autologous blood donation, Masuda and associates have achieved what is expected of contemporary pediatric cardiac programs, namely, the near complete avoidance of homologous blood transfusion in children weighing more than about 12 kg undergoing operations for simple cardiac defects. Their method, however, must be time consuming and anxiety provoking for the child and family, could be an organizational nightmare for higher volume programs, and is not without its own inherent risks. These disadvantages were not analyzed by the authors nor compared with those of other methods of blood conservation. Similar results with transfusion-free cardiac surgery in this weight range have been achieved in other programs for years by use of lower pump primes (350 mL for infants in our institution), modified ultrafiltration, and intraoperative autologous donation and by minimizing blood loss while avoiding wastage of shed blood during the operation. These maneuvers are straightforward and ought to be achievable at the authors' institution. Even for higher risk operations, we are generally able to avoid additional, expensive agents such as aprotinin and commercially made fibrin “glue” while minimizing homologous transfusion. Children who are preoperatively anemic may avoid transfusion by receiving recombinant human erythropoietin and iron. Their application to increase red cell mass before elective operations was approved in the United States in 1996. The safety and efficacy of this approach in children undergoing orthopedic surgery, in children with chronic renal failure, in premature infants with anemia, and in children with cancer have been demonstrated. The availability of an oral form of human erythropoietin strengthens the rationale for using it in children facing cardiac surgery. A prospective study to demonstrate the advantage of human erythropoietin in children undergoing cardiac surgery is sorely needed. When patients do require a transfusion, a component that satisfies multiple needs, including repletion of red cell mass, serum proteins, and functional platelets, should be used. At our institution, we believe these needs are met by using “fresh whole blood” (obtained less than 72 hours before transfusion), especially in infants. With this strategy, infants undergoing an operation who do require a transfusion at our institution are exposed to an average of only 1.7 donors. All cardiac surgeons have the responsibility of applying all reasonable strategies to minimize homologous transfusion. This must be placed in perspective, however, by knowing the actual risks of transfusion in the current era. In fact, the Centers for Disease Control and Prevention have registered only two children in the United States in whom acquired immunodeficiency syndrome has developed as a result of transfusion (for all reasons) in the past 15 years and no cases of transfusion-associated hepatitis C viral infection since 1994. These results are attributable to a national policy of viral screening of blood and to the education of donors. On the other hand, more than two thirds of the world's nations do not have policies to ensure a safe blood supply. Unfortunately, many of these countries have higher prevalence rates of transmittable viruses and yet lack the economic resources to afford expensive pharmacologic means to minimize blood loss during pediatric cardiac surgery. Cardiac programs in these countries may stand to benefit from the policy of multiple autologous donation demonstrated nicely by the authors.

Transfusion-associated or nosocomial hepatitis G virus infection in patients undergoing surgery.

Despite blood donor screening, there are still cases of transfusion-associated hepatitis. From 1988 to 1992, a prospective study was conducted on the incidence of non-A, non-B posttransfusion hepatitis (PTH). The present investigation was designed to determine if transfusion recipients with PTH who are negative for hepatitis C virus (HCV) were positive for hepatitis G virus (HGV). Patients admitted for surgery who had normal liver tests and no transfusions during the previous 6 months were enrolled. Alanine amino transferase levels were determined monthly for 6 months after surgery and for 1 year in the case of PTH (defined as alanine aminotranferase twice the upper limit of normal in two consecutive assays). HGV RNA and E2 antibodies were tested for in samples from transfusion recipients with or without PTH and from nontransfused patients. Of the 308 blood recipients who were enrolled in the study, 21 (6.8%) had PTH. HGV RNA was detected at the onset of hepatitis in 3 patients with PTH (14%), 2 of whom were also anti-HCV and HCV RNA positive. One patient developed E2 antibodies without detectable HGV RNA. Three (10.7%) of 28 recipients of an allogeneic transfusion without PTH developed HGV infection. HGV RNA was also found in two nontransfused patients, which suggests nosocomial transmission of HGV. Some cases of PTH are associated with HGV; most cases of postoperative HGV infection are not associated with liver abnormalities; and most PTH cases are not associated with known hepatotropic viruses.

Hepatitis C Virus and Human Immunodeficiency Virus Infection Can Alter Porphyrin Metabolism and Lead to Porphyria Cutanea Tarda

DAMAGE TO the liver with impairment of hepatic uroporphyrinogen decarboxylase can lead to the development of sporadic porphyria cutanea tarda (PCT). 1 In older studies, agents most commonly implicated in the induction of PCT included alcohol, estrogens, iron, polychlorinated hydrocarbons, and hepatitis B virus. Recently, however, PCT has been frequently associated with infections by other viruses, namely, hepatitis C virus (HCV) 2-5 and human immunodeficiency virus (HIV). 6-9 Two studies in this issue ofArchivesexamine these associations in more detail. 10,11 The purposes of this editorial are to review recent information on this topic and to provide practical guidelines to dermatologists on the evaluation for underlying HCV and HIV infection in patients with photosensitivity or overt PCT. Screening measures to detect hepatitis A and B viruses in the blood supply were developed in the early 1970s, and soon thereafter it became surprisingly clearthat most cases of transfusion-associated hepatitis were not due to these viruses, but to another agent,

Transfusion-associated hepatitis B: past and present.

Thus, it can be concluded that: (1) Hepatitis B, even before the introduction of donor screening for HBsAg, probably never accounted for more than one-quarter of all cases of transfusion-associated hepatitis. (2) As of 1988, the frequency of this viral infection in blood recipients, now that sensitive donor screening for HBsAg is routine, is less than 10%. The exception are multiply transfused populations, such as hemophiliacs, the majority of whom have evidence of current or past exposure to hepatitis B. However, new inactivation procedures are likely to reduce the attack rate in virgin populations of hemophiliacs. (3) Interdiction of paid blood has proved far more effective than donor screening for HBsAg in reducing the overall frequency of transfusion-associated hepatitis. (4) The current requirement that all donors be screened for anti-HBc and ALT as surrogate markers of non-A, non-B hepatitis infection, and for anti-HIV, is likely to reduce the hepatitis B attack rate even more, perhaps to near zero. (5) The long-term outcome of transfusion-associated hepatitis B has not been determined, a task that will remain difficult to accomplish because of the paucity of current cases. Information in this regard will need to be derived from the recall and reevaluation of pedigreed patients who participated in prospective studies that were conducted in the distant past.

Viral hepatitis. 1. Clinical and laboratory aspects and epidemiology.

Hepatitis A and hepatitis B are distinguished clinically by differences in onset and serologically by the presence of hepatitis A antigen or of any one of at least three hepatitis B antigens on the virus particle. At present, hepatitis non-A, non-B can be diagnosed only by exclusion of the other two types. Clinically it resembles hepatitis B. Hepatitis A is most often contracted through the fecal-oral route, and preschool children are at particular risk. Hepatitis B usually is transmitted by parenteral inoculation of virus-containing material. Transmission is now known to occur venereally as well. Since all blood donors now are screened for hepatitis B surface antigen, the cases of transfusion-associated hepatitis that do occur are caused mainly by non-A, non-B virus(es).