Hepatitis C virus infection in patients on maintenance dialysis

Authors:: Marion Muche, MD; Seema Baid-Agrawal, MD
Section Editors:: Steve J Schwab, MD, FACP, FASN; Adrian M Di Bisceglie, MD
Deputy Editors:: Eric N Taylor, MD, MSc, FASN; Allyson Bloom, MD

Literature review current through: Jan 2024.

This topic last updated: Jul 14, 2023.

INTRODUCTION — Hepatitis C virus (HCV) infection is common and associated with significant morbidity and mortality among patients on dialysis.

This topic reviews HCV infection among patients on dialysis, including epidemiology, screening, and prevention.

The treatment of HCV infection among patients with reduced kidney function, including those on dialysis, is discussed elsewhere. (See "Treatment of chronic hepatitis C infection in adults with kidney function impairment".)

General issues related to HCV infection among transplant kidney donors and recipients and recurrent or de novo HCV-related kidney disease in transplant recipients are discussed elsewhere. (See "Hepatitis C virus infection in kidney donors" and "Hepatitis C infection in kidney transplant candidates and recipients".)

EPIDEMIOLOGY — HCV infection is more common in patients on dialysis than in healthy populations. The Dialysis Outcomes and Practice Patterns Study (DOPPS) reported an overall prevalence of 9.9 percent among adult patients on hemodialysis randomly selected from dialysis facilities in high- and middle-income countries (France, Germany, Italy, Japan, Spain, the United Kingdom, China, Russia, Sweden, Belgium, Turkey, Gulf countries, and the United States) [1]. This is compared with a reported global prevalence of approximately 3 percent in the general population. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'Global distribution'.)

HCV infection is more common among patients on dialysis in resource-limited countries, with an approximate incidence of 4.4 cases in 100 patient-years compared with 1 in 100 patients-years in resource-rich countries [2-19].

Within individual countries, there is a wide variation in prevalence of HCV in different dialysis units and geographic regions [4,5,20,21]. In 2002, the prevalence of anti-HCV antibodies ranged from 5.5 to 9.8 percent in various geographic regions in the United States [4]. Similarly, the prevalence ranged from 4 to 14 percent in different dialysis centers in Brazil in a 2011 study [5]. A 2021 meta-analysis of patients on dialysis in Africa found an overall prevalence of anti-HCV antibodies of 23 percent, ranging from 2.3 (Nigeria) to 60.9 percent (Egypt) [22].

HCV infection is declining among patients on dialysis. A meta-analysis including 407 international studies that were conducted between 1989 and 2021 reported an association between later publication year and lower prevalence of HCV in patients on hemodialysis [23]. Among member nations in the European Dialysis and Transplant Association (EDTA), the prevalence of anti-HCV antibodies declined from 21 percent in 1992 to 12.5 percent in 1999 [24-26], and subsequent studies have suggested an ongoing decline [1,8,27,28]. This decline reflects the reduction in use of blood transfusions, ability to screen blood products for HCV, and the implementation of infection control measures within dialysis units.

Nonetheless, outbreaks still occur [29], and the relatively high incidence of anti-HCV antibodies in hemodialysis units is a cause for concern, especially in resource-limited countries [17,30].

RISK FACTORS — The following dialysis-specific risk factors have been identified for HCV infection:

●Dialysis vintage – Among patients on hemodialysis, the risk of seroconversion increases with time on dialysis, particularly after five years [31,32]. By contrast, time on peritoneal dialysis does not appear to be a risk factor [33].

●Mode of dialysis – Patients on peritoneal dialysis are at lower risk for HCV infection compared with patients on hemodialysis [33-35]. In a group of 129 anti-HCV-negative patients on chronic dialysis, the rate of seroconversion was 0.15 per patient-year on hemodialysis compared with 0.03 per patient-year on continuous ambulatory peritoneal dialysis (CAPD) [34]. In fact, the majority of anti-HCV-positive CAPD patients likely acquired HCV infection while on hemodialysis since patients often switch modalities.

Patients on peritoneal dialysis are at lower risk for HCV infection because they have fewer blood transfusions and less parenteral exposure (ie, they do not have an arteriovenous access or require an extracorporeal blood circuit for dialysis). In addition, peritoneal dialysis offers a more isolated environment since it is primarily a home procedure.

Patients on home hemodialysis are also at lower risk than those who receive it at a dialysis unit, likely related to their isolated environment [36].

●Characteristics of the dialysis unit – Characteristics of individual dialysis units that confer an increased risk of HCV infection include a high prevalence of HCV infection in the unit and the personnel-to-patient ratio [2,37-39].

A survey by the Portuguese Society of Nephrology found that, among units with a HCV prevalence of <19 percent, the annual incidence of seroconversion was 2.5 percent [37]. By comparison, among units with a prevalence >60 percent, the annual incidence of seroconversion was 35.3 percent.

Among centers with a high prevalence of patients with HCV infection, the risk of infection may be increased in centers with a low personnel-to-patient ratio [39]. The risk is also higher among patients who are dialyzed in close proximity to patients with HCV infection [37,38].

These observations suggest that nosocomial infection contributes to the high prevalence of HCV infection among patients on hemodialysis. Nosocomial transmission of HCV is proven by studies that demonstrated by viral gene sequence analysis that the same viral strain predominated within individual facilities [40-44]. HCV genotyping of 23 seroconverters in a Belgian hemodialysis unit revealed that 20 were infected with exactly the same HCV strain [40]. Because parts of the HCV genome are extremely variable between strains, these studies provide proof of routes of infection.

●The number of blood transfusions – In earlier studies, HCV seropositivity was associated with receiving a higher number of units of blood products [31]. However, the risk of acquiring posttransfusion HCV infection has declined. In particular, in locations where the blood supply is screened with HCV nucleic acid testing as well as antibody testing, as in resource-rich settings, the risk of HCV infection from transfusion is virtually nonexistent. However, in countries where HCV screening is performed with antibody testing only, blood transfusion can still be a risk factor for HCV infection [32]. Overall, the decreased risk associated with transfusion is due both to HCV screening of blood products and to the decreased use of blood transfusion to treat anemia since the introduction of erythropoietin. (See "Treatment of anemia in patients on dialysis", section on 'Erythropoiesis-stimulating agents (ESAs)'.)

●Other factors – Other risk factors include a history of organ transplantation or injection drug use [32,34,45-48]. A history of previous organ transplantation may reflect transmission from the organ donor [34].

A history of injection drug use was present in 30 percent of anti-HCV antibody-positive patients receiving hemodialysis at the Northwest Kidney Center, Seattle [46] and in 73 percent in two urban hemodialysis units in Miami [47]. (See "Epidemiology and transmission of hepatitis C virus infection".)

PREVENTION — Our approach to the prevention of nosocomial HCV infection within hemodialysis units is consistent with the 2022 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines and with recommendations from the Centers for Disease Control and Prevention (CDC) in the United States [49,50]. Measures are discussed here.

Standard infection control practices and universal precautions — Hemodialysis units should implement and adhere to strict procedures (including universal precautions) aimed at preventing transmission of bloodborne pathogens (table 1). The enforcement of universal precautions has been shown to prevent transmission of HCV in hemodialysis units [51].

As noted above, the major underlying reason for nosocomial HCV infection within hemodialysis units is a breakdown in standard infection control practices [29,52-55] (see 'Risk factors' above). Several outbreaks of HCV infection in hemodialysis units have been associated with a failure to rigidly enforce universal precautions and standard infection control measures [53-55]. Such infractions of standard practice included sharing of a multidose heparin vial between patients with and without HCV infection and failure to change gloves between patients while performing hemodialysis treatments [53-55]. Also suggesting a breakdown in universal precautions, HCV RNA has been detected on the hands of some dialysis personnel despite apparent adherence to standard precautions [56].

Rigorous infection control measures, cleaning and disinfection of all instruments and environmental surfaces that are routinely touched, and a ban on sharing of articles between patients have resulted in a decline in the incidence of HCV infection [57,58]. Hygienic precautions that prevent the transfer between patients of blood or fluids contaminated with blood are shown in the table (table 2). Separate rooms should be used, if possible, for reprocessing and storage of dialyzers from patients with HCV infection.

The peritoneal fluid of patients with HCV infection on peritoneal dialysis is a potential infectious risk. HCV RNA has been demonstrated in the continuous ambulatory peritoneal dialysis (CAPD) effluent [59].

Response to suspected outbreak — Any new case of hepatitis C in a patient on dialysis is likely to be a health facility-associated infection and should be reported to public health authorities.

When there is a new case, all patients who have been exposed should be tested for HCV with HCV RNA (see 'Screening and diagnosis' below). At minimum, this includes all patients dialyzed in the same shift and ideally includes all patients dialyzed at the same facility.

Practices that provide little or no benefit

Isolation of patients with HCV infection — Patients with HCV infection do not require isolation or the use of dedicated dialysis machines. The risk of virus transmission via the internal pathways of the dialysis machine is very low, provided hygienic precautions for dialysis machines are maintained (table 2) [50]. (See 'Standard infection control practices and universal precautions' above.)

Although many early reports suggested that sharing dialysis machines increased the risk of HCV infection [60-62] and using dedicated machines and isolated areas along with universal precautions decreased the incidence of seroconversion [37,58,63-65], the decreased risk was likely due to the enforcement of universal precautions rather than the isolation measures. In a multicenter study from Belgium, no new cases of HCV transmission occurred over a 54-month study period, although none of the participating hemodialysis centers used dedicated machines for anti-HCV antibody-positive patients [51]. The decrease in prevalence in this study occurred after universal precautions were instituted. In addition, after adjusting for confounding factors, neither the Dialysis Outcomes and Practice Patterns Study (DOPPS) nor a study from Italy that included 3492 patients showed a decrease in the incidence of HCV seroconversion associated with isolation measures [2,39].

Use of specific membranes — There is no advantage to using a specific dialysis membrane. To date, a higher prevalence of anti-HCV antibodies among patients on hemodialysis has not been associated with any particular dialysis membrane.

The passage of HCV through any intact dialyzer membrane is unlikely since the viral particles have an estimated diameter of 35 nm, which is much greater than the pores of even the most permeable dialysis membranes, providing there is no disruption of membrane integrity during filter assembly, during the dialysis session itself, or with dialyzer reuse. This has been demonstrated in several studies that showed that both low-flux (cellulose) and high-flux (cellulose-diacetate, polysulfone, and polyacrylonitrile) dialyzers prevent contamination of the dialysis ultrafiltrate with HCV RNA [66-68].

Some investigators have detected HCV RNA by polymerase chain reaction (PCR) in the dialysate of apparently intact polyacrylonitrile membranes but not cellulose membranes [69]. However, the detection of HCV RNA in the dialysate by PCR may imply the presence of fragments of viral RNA but not the infective virus itself, which may not lead to transmission of infection.

Avoidance of "reuse" — Reuse or reprocessing dialyzers does not appear to increase nosocomial transmission of HCV infection, provided infection control measures are employed [4,37,38,70,71]. We agree with the 2022 KDIGO guidelines that suggest dialyzers may be reused if there is adherence to standard infection control procedures [50]. Separate rooms should be used, if possible, for reprocessing and storage of dialyzers from patients with HCV infection.

Both surveillance data from the United States CDC and from a prospective study in 15 hemodialysis units in Belgium showed that the incidence of HCV infection in patients treated in units that reprocessed dialyzers was comparable with those that did not, although separate rooms for reprocessing were not used in the majority of units [4,38].

Similar findings were noted by a Portuguese Society of Nephrology survey [37]. However, in the Portuguese survey, among units that reused dialyzers, the lowest incidence of infection was observed in patients dialyzed in units that used separate rooms to reprocess dialyzers from anti-HCV antibody-positive and anti-HCV antibody-negative patients or that had a ban on reprocessing dialyzers from anti-HCV antibody-positive patients [37]. It remains unclear whether the low rate of infection in centers with dedicated rooms for reprocessing dialyzers from patients with HCV infection reflected a causal relationship or a better adherence to infection control practices.

By contrast, a 2022 meta-analysis identified dialyzer reuse as a potential risk factor for HCV. However, these findings were based only on four studies and need to be interpreted with caution [23].

SCREENING AND DIAGNOSIS — All patients on dialysis should be screened for HCV infection. Methods of screening and diagnosis include testing for anti-HCV antibodies and testing for HCV RNA. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Diagnosis'.)

Our approach is as follows:

●All patients on hemodialysis should be screened for HCV infection upon initiation of hemodialysis or on transfer from another hemodialysis unit. We generally test concurrently for HCV RNA and anti-HCV antibody. HCV antibody production is commonly absent in end-stage kidney disease (ESKD) patients because of the immunocompromised state. False-negative anti-HCV antibody tests have been reported to be as high as 17.9 percent in dialysis units in countries with high HCV prevalence rates [72]. Thus, HCV RNA testing should be performed in all patients if there is clinical suspicion of infection. However, in low-prevalence regions, many centers still test for anti-HCV antibody first followed by nucleic acid testing if the anti-HCV antibody is positive. In low-prevalence countries, anti-HCV antibody testing may be adequate to rule out HCV infection.

Subsequently, patients without evidence of infection should be screened every 6 to 12 months, either by concurrent testing for HCV-RNA and anti-HCV antibody or by testing for anti-HCV antibody followed by a test for HCV RNA if the anti-HCV antibody is positive.

●Patients who develop unexplained, abnormal serum aminotransferase levels should be tested for HCV RNA. However, the frequency of routine serum transaminase testing varies widely (from quarterly to annually) in different dialysis centers. Moreover, the levels of transaminases may be depressed in patients on dialysis and may not reflect the severity of the liver inflammation [73-76] and therefore should not be relied upon for screening for hepatitis. (See "Serum enzymes in patients with kidney failure".)

●Patients on hemodialysis who travel to resource-limited countries and receive hemodialysis should be tested for HCV RNA at 4, 12, and 24 weeks following their return [77].

●If nosocomial infection is suspected, all patients who have been exposed should be tested for HCV RNA at 4, 12, and 24 weeks following potential exposure. At minimum, this includes all patients dialyzed in the same shift and ideally includes all patients dialyzed at the same facility. Such patients should also have serum aminotransferases measured at 4 and 12 weeks and anti-HCV antibody measured at 12 and 24 weeks. (See "Clinical manifestations, diagnosis, and treatment of acute hepatitis C virus infection in adults", section on 'Patients with discrete HCV exposure'.)

As noted above, any new case of hepatitis C in a patient on dialysis is likely to be health facility associated and should be considered a result of nosocomial infection. (See 'Response to suspected outbreak' above.)

A positive HCV RNA result is evidence of HCV infection. Patients with positive tests should be evaluated further to determine the extent of liver disease through physical exam, laboratory testing, and consideration of liver biopsy. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Additional evaluation'.)

As direct HCV-RNA testing is expensive and may sometimes not be technically available in resource-poor countries, the quantitative determination of the HCV core antigen (HCVcAg) in the serum or plasma using a monoclonal antibody has been proposed as a cheaper alternative to direct HCV-RNA testing [78]. However, the sensitivity of HCVcAg is considerably lower than that of HCV RNA testing [79]. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'HCV core antigen test'.)

Occult HCV infection is defined as the detection of HCV RNA in peripheral blood mononuclear cells and/or hepatocytes in the absence of positive HCV RNA in the serum, although its clinical significance has not been proven. We do not routinely screen patients who are negative for HCV RNA for occult HCV infection in a low-prevalence setting. The prevalence of occult HCV infection has been found to be very low in patients on maintenance hemodialysis in a low-prevalence region [27]. An exception is patients with unexplained impairment of liver function in the absence of serum HCV RNA in high-prevalence units/regions, among whom we may test for occult HCV infection in peripheral blood mononuclear cells [80]. It is reasonable to refer such patients for evaluation of liver disease, similar to those with positive HCV RNA, since occult HCV infection has been proposed but not confirmed to affect viral reactivation and disease progression and the risk of HCV transmission within dialysis units.

EVALUATION OF LIVER DISEASE — In general, the evaluation of liver disease in patients with HCV infection on dialysis is similar to that in the general population and is discussed in detail elsewhere. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection".)

However, there are dialysis-specific considerations in the noninvasive staging of hepatic fibrosis:

●Blood tests like the aspartate aminotransferase to platelet ratio index (APRI) or Fibrosis-4 index (FIB-4) score may yield a false negative result in patients on dialysis, as transaminase levels in patients on dialysis tend to fall within the lower end of the range of normal values. (See "Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations".)

●Although imaging such as transient elastography (TE), which uses shear wave imaging to estimate liver stiffness, has been shown to be reasonably accurate for the evaluation of liver fibrosis in patients on hemodialysis [81], TE should be performed postdialysis. Liver stiffness measurements have been shown to decrease significantly after a hemodialysis session, and the decrease is associated with the amount of fluid removed [82-84]. (See "Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations".)

When liver biopsy is indicated, end-stage kidney disease (ESKD) does not appear to increase the risk of bleeding with percutaneous biopsy [85]. To decrease the risk of postinterventional bleeding in patients with coagulation disorders and in patients on peritoneal dialysis, a transjugular approach instead of a percutaneous approach can be used [86]. The indications for liver biopsy in patients with hepatitis C are discussed separately. (See "Hepatitis C infection in kidney transplant candidates and recipients", section on 'HCV evaluation of transplant candidates' and "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'Assessment of fibrosis stage'.)

Among patients with advanced fibrosis and cirrhosis related to HCV, screening for hepatocellular carcinoma (typically with abdominal ultrasound) should be performed every six months. The methods of surveillance are discussed separately. (See "Surveillance for hepatocellular carcinoma in adults", section on 'Our approach to surveillance'.)

CLINICAL COURSE AND PROGNOSIS — The clinical presentation of HCV infection in patients on dialysis is similar to that in the general population; most patients have minimal or no symptoms. (See "Clinical manifestations and natural history of chronic hepatitis C virus infection", section on 'Clinical features'.)

Among patients with chronic HCV infection, the rate of progression of hepatic fibrosis is highly variable and depends on other risk factors for liver disease (eg, HIV or hepatitis B virus [HBV] coinfection, alcohol use, obesity). Many patients may develop only mild hepatic inflammation and fibrosis in their lifetime. Data on the rate of fibrosis progression in patients with HCV and end-stage kidney disease (ESKD) are mostly limited to single-center cross-sectional studies and a few prospective studies with relatively short follow-up and no histologic evaluation [77]. Given the overall lower life expectancy of patients on hemodialysis, complications like decompensated cirrhosis and hepatocellular carcinoma may not have time to develop. Among HCV-seropositive patients who undergo a liver biopsy as part of the evaluation for kidney transplantation, the prevalence of advanced fibrosis and cirrhosis has ranged from 10 to 25 percent [87-89].

Despite competing comorbidities, HCV infection is independently associated with decreased survival among patients with ESKD [77]. In a 2019 meta-analysis of 23 observational studies and 574,081 patients on dialysis, HCV-seropositive status was associated with a higher risk of death (hazard ratio [HR] 1.26, 95% CI 1.18-1.34) [90]. This and other analyses also demonstrated increased cardiovascular risk among patients on dialysis with HCV infection [91,92], which is consistent with observations in the general population. (See "Acute hemodialysis prescription".)

Patients with HCV infection who undergo kidney transplantation have decreased mortality compared with patients with HCV infection on dialysis. This issue is discussed elsewhere. (See "Hepatitis C infection in kidney transplant candidates and recipients".)

TREATMENT — Cure of HCV infection prior to the development of decompensated cirrhosis results in decreased all-cause mortality, liver-related death, need for liver transplantation, hepatocellular carcinoma rates, and liver-related complications. Elimination of HCV infection among patients on dialysis also reduces the risk of health care–associated transmission and outbreaks [93-96]. Details regarding the rationale, candidacy, safety, and selection of HCV therapy in patients with kidney function impairment (including those on dialysis) are discussed elsewhere. (See "Treatment of chronic hepatitis C infection in adults with kidney function impairment".)

Considerations for managing HCV infection in patients on dialysis who are kidney transplant candidates are also discussed elsewhere. (See "Hepatitis C infection in kidney transplant candidates and recipients".)

MANAGEMENT OF EXPOSED HEALTH CARE PERSONNEL (NEEDLESTICK INJURY) — The reported risk of transmission of HCV from patients with infection to medical staff by needlestick injury ranges from 0 to 10 percent [97-101]. In one study, transmission occurred only from hollow-bore needles and not from any other sharps [101]. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers".)

Despite the risk, the prevalence of HCV seropositivity among dialysis staff is comparable with that in blood donors. In one study in which 16 percent of dialysis centers in the United States tested staff members for anti-HCV antibodies, among the 6236 staff members tested, the prevalence of anti-HCV antibodies was 2 percent (range 0 to 10 percent in centers with at least 20 staff members) [21].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hepatitis C virus infection" and "Society guideline links: Dialysis".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – The prevalence of hepatitis C virus (HCV) infection is higher among patients on dialysis than in other populations, particularly in resource-limited countries. (See 'Introduction' above and 'Epidemiology' above.)

●Risk factors – Dialysis-specific risk factors for HCV infection include dialysis vintage, hemodialysis compared with peritoneal dialysis, a high prevalence of HCV infection in the individual dialysis unit, and a low personnel-to-patient ratio in the individual dialysis unit. If patients with HCV viremia are being dialyzed in the same unit as patients without HCV viremia, there is a risk of health care–associated transmission. (See 'Risk factors' above.)

●Prevention – Dialysis units should implement and adhere to strict procedures (including universal precautions) aimed at preventing transmission of bloodborne pathogens (table 1). Patients with HCV infection do not require isolation or the use of dedicated dialysis machines or specific dialysis membranes. Reuse or reprocessing dialyzers does not appear to increase nosocomial transmission of HCV infection, provided infection control measures are employed. (See 'Prevention' above.)

●Screening and diagnosis – All patients on dialysis should be screened for HCV infection. Because of the risk of a false-negative anti-HCV antibody in the setting of end-stage kidney disease (ESKD), we generally screen patients on dialysis with anti-HCV antibody and HCV RNA testing concurrently. (See 'Screening and diagnosis' above.)

●Treatment – Decisions to initiate antiviral treatment in patients on dialysis should be undertaken on a case-by-case basis, taking into account the anticipated benefits of HCV therapy, life expectancy, comorbidities, and potential for kidney transplant candidacy. The details regarding rationale, candidacy, safety, and selection of HCV therapy in patients with kidney function impairment (including those on dialysis) are presented separately. (See "Treatment of chronic hepatitis C infection in adults with kidney function impairment" and "Hepatitis C infection in kidney transplant candidates and recipients".)

●Prognosis – HCV infection decreases survival among patients with ESKD. (See 'Clinical course and prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Svetlozar Natov, MD and Brian JG Pereira, MD who contributed to earlier versions of this topic review.

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Hepatitis C virus infection in patients on maintenance dialysis

References