Liver Disease and Gastrointestinal Disorders in Dialysis Patients

Interpretation of Diagnostic Tests

Hepatitis B surface antigen (HBsAg) is the first marker of HBV detectable in serum in acute infection. By the time clinical and biochemical hepatitis is present after an incubation period of up to 140 days, other serologic markers of HBV infection appear, including antibody to HBV core antigen (anti-HBc). Hepatitis B core antigen, a marker of viral replication found in infected hepatocytes, does not circulate in serum. However, its corresponding antibody (anti-HBc) does. Documented HBsAg positivity in serum for 6 months or more suggests chronic HBV with a low likelihood of subsequent spontaneous resolution. Chronic HBV is diagnosed by the absence of immunoglobulin M (IgM) anti-HBc antibody. IgM anti-HBc antibody is a marker of acute or recent acute hepatitis B and is detectable for 6 months after infection, whereas IgG anti-HBc is lifelong. If acute HBV resolves, neutralizing antibody against HBsAg (anti-HBs) develops. If HBV infection becomes chronic, other HBV markers—including HBV viremia (HBV DNA) and hepatitis E antigen (HBeAg)—should be sought. Both of these markers imply viral replication and, thus, greater infectivity, although any patient who is HBsAg positive is potentially infectious.

Natural History of Hepatitis B Virus in the Dialysis Population

The course of HBV infections is frequently asymptomatic and indolent among patients on maintenance dialysis; some symptoms that typically occur in nondialysis patients with HBV (i.e., asthenia, fatigue, and cognitive impairment) are common in the dialysis population irrespective of their HBsAg serologic status. Evaluation of the seriousness of HBV infection in patients on long-term dialysis is hampered by the observation that serum aminotransferase levels are commonly lower in patients on dialysis or with predialysis chronic kidney disease than among individuals with intact kidney function. No marked elevations of liver enzymes have been observed, but serum aminotransferase and gamma-glutamyl transpeptidase are frequently greater in HBsAg-positive than HBsAg-negative individuals on long-term dialysis. In contrast to renal transplant recipients with chronic HBV infection, there is no evidence of accelerated progression to decompensated cirrhosis or HCC.

Mortality is an unequivocal endpoint in the natural history of HBV, but data concerning the relationship between HBV infection and risk for death among HBV-infected patients on long-term dialysis are not abundant. One survey from financially constrained dialysis facilities has shown that the death rate was greater among HBsAg-seropositive than HBsAg-seronegative patients undergoing long-term dialysis. Liver failure was more common in HBsAg-seropositive than HBsAg-seronegative patients. These investigators concluded that the clinical outcomes of renal replacement therapy are apt to be adversely affected by inadequate dialysis or infections due to limited financial resources.

Epidemiology of Hepatitis B Virus in Dialysis Facilities

Soon after the discovery of HBV (late 1960s), hepatitis B was recognized as an important threat for staff and patients within dialysis facilities. In 1977, the Centers for Disease Control and Prevention (CDC) issued isolation guidelines to prevent the transmission of HBV within dialysis facilities. In addition to the CDC recommendations, the screening of blood products for HBsAg and anti-HBc antibody and a lower need for blood products resulted in a fall in the incidence and prevalence of HBV among patients and staff within dialysis facilities from North America and western Europe during the period 1974 to 1995. The most recent and large ( n = 263,820) survey on the epidemiology of HBV among patients undergoing long-term dialysis in the developed world remains the 2002 survey by the CDC. It reported a 1.0% mean prevalence of HBsAg-seropositive patients; the incidence of HBV infection was 0.12%. HBV appears more common in many low-income countries where the rate of patients on maintenance dialysis who are chronic HBsAg carriers ranges between 1% and 15%.

The delivery of health care in the developed world has changed over recent years, leading to an increased number of patients treated outside of acute care hospitals. Thus, numerous outbreaks of HBV infection in nonhospital health care settings, including dialysis facilities, have been reported. Lack of compliance to standard and dialysis-specific infection control precautions is likely the most important cause of patient-to-patient transmission of HBV in dialysis facilities, according to a recent systematic review of reports on outbreaks.