Table 12.1 describes diagnostic tests for hepatitis B virus and their interpretation. Serum hepatitis B surface antigen (HBsAg) is the first detectable serum marker in acute HBV infection. After an incubation period of up to 140 days, the patient may develop symptoms such as malaise and anorexia, or become frankly icteric. By this time, other serum markers of HBV infection appear, including antibody to the hepatitis B core antigen (anti-HBc). Hepatitis B core antigen (HBcAg) is present exclusively in nuclei of infected hepatocytes, but the corresponding antibody circulates in blood. During acute HBV infection, anti-HBc antibody is predominantly immunoglobulin M (IgM). Over the subsequent 6 months, IgM levels decline, whereas IgG anti-HBc levels persist. Although anti-HBc is not a neutralizing antibody, it is the most durable marker of prior HBV infection. With successful resolution of acute HBV, protective antibody against HBsAg (anti-HBs) appears, signifying immunity against HBV. Anti-HBs antibody tends to decline and even disappear over time, leaving an “isolated” core antibody (IgG anti-HBc) as the only marker of prior HBV infection. If
HBsAg persists for more than 3 months, HBV DNA and hepatitis B e antigen (HBeAg) levels should be checked to assess level of active viral replication.

Only about 5% of infected immunocompetent adults fail to recover from acute hepatitis B infection and develop chronic hepatitis B. In these individuals, HBsAg persists in serum, and anti-HBs fails to appear. Chronicity is more likely in individuals with impaired immune response such as uremic patients, elderly patients, and children. Symptomatic acute HBV with jaundice is more likely to lead to successful clearance of HBV infection than a subclinical acute HBV. This apparent paradox is explained by the prominent role host immunity plays in the expression of the clinical course of HBV. The immune response during icteric acute HBV infection results in more liver injury with more symptoms, but also a greater likelihood of recovery compared with symptomatically milder acute HBV. Two phases of chronic HBV infection can be distinguished. In the early months and years of chronic HBV infection, the “replicative” phase occurs, which is often accompanied by necroinflammatory changes in the liver and elevated aminotransferase levels in serum. The “replicative phase” is characterized by active viral replication: HBeAg and high titers of HBV DNA are detectable in serum. The second phase of chronic HBV infection is the “nonreplicative” phase, which is often heralded by a transient increase in aminotransferase levels. The nonreplicative phase follows HBeAg clearance. With HBeAg loss, antibodies to HBeAg appear in serum, HBV DNA levels decrease, and, generally, liver disease activity subsides both biochemically and histologically. After HBeAg clearance, infectivity is much reduced, but low levels of HBV DNA may persist for variable periods of time. Patients with persistent HBsAg positivity and normal serum aminotransferase activity were previously defined as healthy carriers of HBV but are now referred to as inactive carriers. Although these patients usually have persistently normal alanine transaminase (ALT) and aspartate transaminase (AST) levels and absent or lower serum HBV DNA (<2000 IU/mL), they still are at risk for developing progressive liver disease triggered by immunosuppression after renal transplantation. The HBV genome shows significant heterogeneity and various mutant forms of HBV have been identified in which amino acid substitutions at crucial sites in the viral genome occur. An important subset of patients clear HBeAg and develop the corresponding anti-HBe antibody, but they continue to have active replication with strongly positive serum HBV DNA with elevated transaminases. This
HBeAg-negative form of chronic HBV is characterized clinically by a more poorly sustained response to antiviral therapy than is found in chronically infected patients who remain HBeAg positive. The HBeAg-negative form of chronic HBV, a later stage of chronic HBV infection, is becoming more prevalent as vaccination programs reduce the incidence of acute HBV infection.

HBV infection is a major cause of morbidity, with as many as 350 million people infected worldwide, resulting in an estimated 1 million deaths per year. Despite the availability of a vaccine since the early 1980s, HBV remains a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Large-scale immigration to Western Europe and North America from areas of higher prevalence of chronic HBV such as such Asia and sub-Saharan Africa has resulted in reservoirs of HBV infection in areas with large immigrant populations. Eight HBV genotypes have been identified (A to H). Specific HBV genotype may be associated with more severe liver disease; for instance, genotype C, common in Asians, confers a high risk for the development of cirrhosis and hepatocellular carcinoma. HBV genotyping is increasingly being recommended in routine clinical practice to guide management.

Prevention of HBV acquisition in dialysis centers has been an important aspect of its management in patients with chronic kidney disease (CKD). The incidence and prevalence of HBV infection in dialysis patients in developed countries has fallen since the mid-1970s as a result of strict attention to relatively simple precautions. Outbreaks of HBV infection in dialysis units are now usually a result of nonadherence to these precautions, which include serologic surveillance, isolation of HBV-infected patients, use of dedicated dialysis machines, and rigorous disinfection. HBsAg rates remain higher in patients on dialysis in less developed countries where HBV remains prevalent in the population as a whole. Despite the availability of HBV vaccination since the early 1980s, recent surveys in the United States reveal that many patients on chronic dialysis have not been vaccinated. Although response to vaccination with development of protective levels of anti-HBs is not universal in this population, at least 60% of chronic dialysis patients do respond adequately. Hepatitis B vaccine should be recommended in all candidates with no previous exposure, and anti-HBV titer should be checked to confirm immunity. Subcutaneous administration or higher or repeated doses should be considered in patients with inadequate response. Periodic antibody testing should be considered because of a higher rate of loss of anti-HBs in uremic patients.

The prevalence of HBV infection among renal transplant candidates has decreased because of less HBV infection in the dialysis population. Because of concern about post-transplantation progression of liver disease, HBV infection had been regarded as a relative contraindication to renal transplantation. HBV infection in transplant recipients may be associated with only minor elevations of aminotransferase levels despite histologic progression. Known risk factors for progression of HBV-related liver disease include alcohol use; longer duration of infection; high serum levels of HBV DNA; genotype C; coinfection with hepatitis C and D; HIV infection; and immunosuppression. Immunosuppression may increase HBV replication by various mechanisms, including diminished activity of cytotoxic T lymphocytes. In addition, the HBV genome contains a glucocorticoid-responsive element that augments HBV replication. Azathioprine and the calcineurin inhibitors may also enhance HBV replication.

The adverse effect of immunosuppressive therapy on HBV infection has been recognized in several clinical settings. Severe, even fatal, HBV reactivation is noted in patients who receive systemic chemotherapy. Reactivation of HBV
has been observed in renal transplant recipients whose prior markers of HBV infection had resolved with reappearance of HBsAg in serum despite its absence before transplantation. Liver transplantation in HBV-infected patients is associated with frequent graft reinfection followed by progressive liver disease if immunoprophylaxis is not given.

The adverse effect of HBsAg positivity on patient survival in renal transplant recipients is well established. The effect of HBsAg status on graft survival is less clear, although early reports had suggested that graft survival might be enhanced in HBV-infected recipients as a result of a diminished immune response resulting from chronic viral infection.

Figure 12.1 illustrates an approach to the kidney transplant candidate with a diagnosis of HBV. Liver biopsy should be incorporated in the evaluation of renal transplant candidates with HBsAg because it is difficult, on clinical grounds alone, to estimate the severity of liver disease in CKD patients. Aminotransferase levels may be spuriously normal despite necroinflammatory changes on biopsy. Desmopressin acetate (DDAVP) should be administered by intravenous infusion at the time of biopsy to counteract uremic platelet dysfunction. A decision concerning transplant candidacy in HBsAg-positive patients should be based on both liver histology and evaluation of HBV replication by serum markers (i.e., HBeAg and HBV DNA). The absence of serum marker of replication, that is, HBV DNA or HBeAg positivity, before transplantation, however, does not preclude reactivation of HBV infection after transplantation. Patients with established cirrhosis (stage IV) on liver biopsy are at risk for frank hepatic decompensation after transplantation, and kidney transplantation alone without simultaneous liver transplantation is contraindicated. In patients with

Stay updated, free articles. Join our Telegram channel

Join