the 1990s

The 1990s mark a decisive turning point in the history of hepatitis C virus infection in hemodialysis. At the beginning of the decade, hemodialysis patients were recognized as a high-risk population, carrying the legacy of non-A non-B hepatitis, frequent transfusions, and a substantial burden of infection acquired through medical care. During the decade, improved blood-donor screening sharply reduced transfusion-associated risk, but the epidemiological focus moved inward, toward the dialysis station itself: shared care environments, contaminated surfaces, equipment handling, and failures of routine hygiene. The period therefore stands between two models of transmission, with the dominant explanation changing from exposure through blood products to continuing nosocomial spread within hemodialysis units.

A High-Risk Population at the Decade’s Beginning

The early 1990s inherited a problem that had become visible as soon as reliable serological tests for hepatitis C virus became available. Hemodialysis patients showed high prevalence and incidence of infection, and earlier reports of non-A non-B hepatitis outbreaks had already established that dialysis units could sustain transmission. The burden could not be explained by transfusion alone. In several studies, prevalence correlated strongly with time spent on dialysis even after the transfusional burden was taken into account. Infection was also more common among hemodialysis patients than among patients receiving peritoneal dialysis or home hemodialysis, and substantial prevalence was found among patients who had never received a transfusion. The pattern made the hemodialysis unit an epidemiological setting in its own right. Patients were repeatedly exposed to procedures, staff movements, equipment, and surfaces in a tightly organized clinical environment. The distinction between an infection brought into the unit and one acquired there was not merely historical: it determined whether prevention depended chiefly on safer blood or on the discipline of everyday clinical practice. In the early 1990s, the evidence increasingly pointed toward both sources, with nosocomial transmission requiring particular attention.

The Decline of Transfusion-Related Risk

The decade brought a dramatic reduction in the danger posed by transfused blood. In the 1980s, the risk of posttransfusion hepatitis C had been approximately 0.5% per blood unit. With rapidly improving screening of blood donors, that risk fell in the United States to around 0.0001%, or roughly one case per million blood units, with similarly substantial improvements in other Western countries. The widespread availability of erythropoiesis-stimulating agents in the early 1990s also reduced the need for transfusion among hemodialysis patients, reinforcing the effect of safer blood supplies. This change did not eliminate hepatitis C from the dialysis population. Instead, it altered the question that clinicians and investigators had to ask. Once transfusions became a much less plausible explanation for new infections, attention turned to the possibility that the dialysis environment itself was permitting bloodborne transmission. The hemodialysis community became increasingly concerned with nosocomial infection, and infection-control practices moved from a supporting consideration to the center of prevention.

Isolation, Hygiene, and Unsettled Policy

The response differed between countries and individual units. Spain, where prevalence had initially exceeded 30%, adopted isolation of hepatitis C virus-positive patients by ward or monitor and reinforced hygienic precautions. Most units in Belgium chose to reinforce hygienic precautions without adopting isolation. The disagreement reflected competing practical and epidemiological arguments. Opponents of isolation emphasized the long interval between infection and seroconversion, the lower infectivity of hepatitis C virus compared with hepatitis B virus, the logistical burden of creating multiple wards for patients with different infection statuses, and the possibility that isolation could expose patients to multiple hepatitis C virus genotypes. Supporters argued that every feasible measure should be used, especially in units with high recent seroconversion rates. In many countries, prevalence and incidence subsequently declined. Yet the evidence could not establish that isolation itself caused the improvement, because the available studies were before-and-after or A-B comparisons without randomized controls or even consistent control groups. The decrease therefore belonged to a broader package of changing conditions, including safer blood, reduced transfusion requirements, improved awareness, and better hygiene. The decade’s policy debate revealed a recurring tension in infection control: visible separation of infected patients could signal seriousness, but invisible procedural failures might remain the more important mechanism of spread.

Molecular Evidence and the Transmission Route

From the mid-1990s onward, molecular virology provided unusually direct evidence that nosocomial transmission was occurring. Phylogenetic analyses of hepatitis C virus isolates collected from patients in the same hemodialysis unit identified clusters of closely related viruses, both in individual units with high seroconversion rates and in multicenter studies. Because portions of the hepatitis C virus genome are highly variable and accumulate frequent mutations, sequencing could function as a genetic fingerprint, allowing investigators to compare isolates and estimate the probability that infections came from a common source. The molecular evidence supported transmission within units but did not usually identify the precise physical route. A systematic review by the Kidney Disease Improving Global Outcomes workgroup examined 20 studies involving newly diagnosed hepatitis C virus-positive hemodialysis patients and already infected source patients, together with epidemiological information. None of the studies conclusively established a specific transmission pathway, a limitation expected when investigations begin after the event. Nevertheless, every study suggested that failures in infection-control procedures were the probable cause of new cases. The internal fluid pathway of the dialysis machine appeared to play, at most, a small role. Transmission through that route was considered possible in only one study. In 18 of the 20 studies, some or all newly infected patients had not shared a dialysis machine with the presumed source patient; they had either been dialyzed at the same time or had been assigned machines different from those used by hepatitis C virus-positive patients. The evidence consequently shifted responsibility away from the machine’s internal circuit and toward the wider clinical environment and the handling of patients and equipment.

The Decade’s Lasting Consequences

The 1990s established the prevention principles later emphasized by Kidney Disease Improving Global Outcomes. Dedicated dialysis machines for hepatitis C virus-infected patients were not recommended, because the available molecular and observational evidence did not show that machine separation addressed the principal route of transmission. Isolation in a separate ward was likewise not accepted as a substitute for strict infection-control procedures. Later prospective observational studies, including the Dialysis Outcomes and Practice Patterns Study and an Italian study, found after adjustment for potential confounders that isolation did not protect against transmission. The practical lesson was laborious but concrete: staff needed to wash their hands before and after contact with each patient or the equipment at that patient’s dialysis station, use alcohol gel when hands were not visibly contaminated, wear disposable gloves when caring for patients or touching potentially contaminated surfaces, and remove gloves before leaving the station. Single-use items had to be discarded after one patient, reusable items disinfected or dedicated to a single patient, and contaminated surfaces cleaned after every session. These measures, rather than the architecture of separation alone, became the durable legacy of the decade. The 1990s also shaped the later epidemiology of hepatitis C in hemodialysis. As infections acquired after the start of dialysis declined, it became increasingly apparent in the following decades that many hepatitis C virus-positive patients had been infected before renal replacement therapy. Possible histories included transfusions before appropriate blood and organ-donor screening, intravenous drug use, and remote healthcare-related transmission. Hepatitis C virus also remained relevant because it could cause cryoglobulinemic or membranoproliferative glomerulonephritis that progressed not infrequently to end-stage renal disease. The decade thus reduced one pathway without removing the disease from dialysis care, leaving a population whose infections were often older and whose long-term risks, including cirrhosis and hepatocellular carcinoma, required continuing surveillance.