Treatment of Hepatitis C Virus Infection in Patients with End-stage Renal Disease

Chen-Hua Liu; Jia-Horng Kao

Disclosures

J Gastroenterol Hepatol. 2011;26(2):228-239. 

In This Article

Diagnosis and Evaluation of HCV Infection in ESRD Patients

Serological Assays

There are two types of anti-HCV assays using structural and non-structural (NS) HCV proteins to detect HCV antibodies: enzyme immunoassay (EIA) and recombinant immunoblotting assay (RIBA). EIA is more commonly used due to its simplicity and reduced cost. EIA-1 (first-generation EIA) contained a single recombinant antigen in the HCV NS4 region, and was flawed by high false-negative and false-positive rates. The following two successive generations of EIA (EIA-2 and EIA-3), containing additional antigens in the core, NS3, NS4, and NS5 regions, further increase the sensitivity and specificity. Such commercial assays are now widely used in clinical practice. Although RIBA is considered reproducible and confirmative to diagnose HCV infection for positive EIA samples, it is rarely used after the introduction of sensitive molecular assays to detect (or quantify) circulating HCV-RNA.

In ESRD patients receiving maintenance dialysis, previous studies showed that the false-negative rates of EIA-2 were 2.6% and 7%, respectively, to diagnose HCV infection, taking HCV-RNA as the reference standard.[41,65] The EIA-3 provided excellent accuracy, with 0–0.23% false-negative rates. Thus, EIA-3 is an effective screening tool for HCV infection in patients with ESRD.[66,67]

Virological Assays

HCV-RNA is the direct marker of HCV replication. It can be used to estimate the level of viral replication in the liver and to monitor the effectiveness of treatment response to antiviral therapy. HCV-RNA can be determined qualitatively or quantitatively on the basis of different molecular biological techniques. In addition, the HCV genotype is the intrinsic characteristic of the infected HCV strains, and remains stable during the course of chronic HCV infection. The evaluation of HCV-RNA and the genotype can help clinicians determine the optimal duration and dosage of interferon (IFN)-based therapy.

Several studies have found that the HCV-RNA level is transiently decreased during hemodialysis, but gradually returns to baseline level within 48 h.[68–70] Various mechanisms, including the adsorption of HCV onto the dialysis membrane, destruction of HCV particles, escape of HCV into the dialysate, or increased plasma IFN-α levels during the dialysis, might be associated this particular phenomenon.[71,72] It is recommended that the viral load should be determined prior to hemodialysis to avoid the possibility of underestimation. Although the distribution of HCV genotypes varies widely among different geographic regions, HCV genotypes 1 and 2 predominate in ESRD patients with chronic hepatitis C, regardless of geographic areas.[73–76]

Biochemical Assays

Although the serum ALT level is used to screen liver diseases in the general population, it is known that ESRD itself lowers ALT levels.[77,78] Thus, the optimized cut-off ALT level to detect HCV viremia is approximately 0.4–0.45 times the ULN of the conventional level (typically 40 IU/L).[79,80]

Invasive and Non-invasive Tests to Evaluate Liver Histology

Compared to non-uremic HCV patients, ESRD patients with chronic hepatitis C have milder hepatic necroinflammation and fibrosis.[81–83] A longer duration of infection, advanced age at infection, elevated serum aspartate aminotransferase (AST), and severe hepatic necroinflammation on liver biopsy are associated with significant hepatic fibrosis.[83,84]

Clinically, percutaneous liver biopsy is the gold standard to assess the liver histology in ESRD patients with chronic hepatitis C, by which physicians can evaluate the eligibility for RT, the long-term prognosis and the necessity for IFN-based therapy.[85,86] However, liver biopsy is limited by poor patient acceptance, potentially serious bleeding events, and sampling and interpretation errors. These issues have stimulated a search for non-invasive means to predict the severity of liver histology.[87–89]

Two studies indicated that the AST : platelet ratio index (APRI), based on simple blood tests, is useful in predicting the severity of hepatic fibrosis in ESRD patients with chronic hepatitis C.[90,91] However, the major strength of APRI is to exclude patients with significant hepatic fibrosis (≥F2) when the cut-off level is set at <0.40; this saves, at most, 50% of patients from being correctly diagnosed without the need for liver biopsy. The recently-introduced transient elastography (Fibroscan; Echosense, Paris, France) shows superior diagnostic accuracy to APRI, with 69% and 82% of ESRD patients with mild (≥F1) and significant (≥F2) hepatic fibrosis correctly diagnosed without the need for liver biopsy.[92]

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