Hepatitis C Virus Infection Among Hematopoietic Cell Transplant Donors and Recipients

Publication Date: August 6, 2015
Last Updated: March 14, 2022

Recommendations

Natural History of HCV Infection in HCT Recipients

In all HCT survivors with active HCV infection, cofactors that can lead to fibrosis should be addressed. Patients should be counseled to avoid excessive weight gain, ethanol and medications or herbal supplements that are hepatotoxic, as well as on treatment of other causes of liver disease (nonalcoholic fatty liver disease, hepatitis B virus, HIV, and extrahepatic obstruction), (CI)
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  • and mobilization of excess iron.
(CIIa)
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All HCV-infected long-term HCT survivors should be evaluated for progression of liver disease every 6 to 12 months with a hepatic function panel, complete blood cell count, and evaluation of prothrombin time/international normalized ratio. (CI)
If fibrosis is suspected in long-term HCT survivors, noninvasive tests such as serologic panels and transient elastography can be used to evaluate for the presence of advanced fibrosis (Scoring System for Histological Stage Metavir score ≥F3) and cirrhosis (Metavir score F4).
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HCV-infected HCT recipients should be vaccinated against hepatitis A virus and hepatitis B virus following HCT immunization protocols. ()
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Donors and HCT candidates with HCV infection should be counseled to use appropriate precautions to prevent transmission of HCV to others. (CI)
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For HCV-infected HCT long-term survivors with advanced fibrosis (Metavir score ≥F3), surveillance for hepatocellular carcinoma (HCC) with ultrasonography every 6 months is recommended. (CI)
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For patients with cirrhosis, endoscopic surveillance for esophageal varices is recommended. (AI)
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HCT recipients who develop end-stage liver disease can be considered for liver transplant; in rare cases, a living donor liver transplant from the original hematopoietic cell donor may be feasible. (CI)
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HCV Screening in Donors of Hematopoietic Stem Cells, HCT Candidates, and Long-Term Survivors

All hematopoietic cell donors should be screened for HCV within 30 days before cell harvest with FDA-approved HCV antibody (anti-HCV) and RNA testing in accordance with the Foundation for the Accreditation of Cellular Therapies (FACT) standards and FDA guidance. (CI)
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All HCT candidates should be screened for HCV with FDA-approved anti-HCV testing. (CI)
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All long-term survivors of HCT should be screened for HCV infection based on the current recommendations for screening in non-HCT recipients, with special attention to those with epidemiologic risk factors, including those transplanted in the era before routine donor and blood product screening. (CI)
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Impact of HCV Infection on Eligibility to Donate Hematopoietic Stem Cells or Undergo HCT

HCV infection in donors or potential HCT recipients should not be an absolute contraindication for HCT. (CI)
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The risk of HCV transmission is extremely low when seronegative and HCV RNA–negative HCT candidates receive HCT from donors of hematopoietic stem cells with positive anti-HCV and undetectable HCV RNA. (CI)
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HCV-infected donors should be assessed for advanced chronic liver disease and other extrahepatic manifestations of HCV to recommend an optimal management of their disease. (CI)
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HCV-infected donors should be screened for other coinfections (eg, HIV). HIV-HCV–coinfected individuals should not be considered as donors for HIV-seronegative recipients, according to standard HCT guidelines. ()
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HCV-infected HCT candidates requiring HCT and for whom there is no alternative donor can proceed with HCT from a donor also infected with HCV provided the recipient has full understanding of the potential consequences given the viral characteristics of the donors' HCV infections. (CIIb)
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If the donor is HCV RNA positive and transplantation to an HCV-infected or -uninfected recipient is considered, the donor should start antiviral therapy immediately with the goal of reducing the infectious potential of the donor, ideally attaining undetectable plasma HCV RNA in the donor before stem cell harvest. (CI)
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Selection of HCV-infected candidates for HCT should be based on the extent of liver fibrosis and degree of portal hypertension. (CI)
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Monitoring HCV in HCT Recipients with Chronic HCV Infection

In HCT recipients with chronic HCV infection, ALT level should be evaluated at entry into care, 2 to 8 weeks after completion of the conditioning regimen, every 2 to 8 weeks during maintenance chemotherapy or immunosuppressive treatment, and every 3 to 6 months thereafter. (CIIb)
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In HCT recipients with chronic HCV infection, routine monitoring of HCV RNA is not recommended. However, viral load should be considered for patients who have an unexplained elevation of ALT (class II, level C). HCV RNA should be measured in all patients at entry into care, and monitoring of viral load should be performed in patients receiving HCV treatment according to the AASLD-IDSA HCV guidance (http://www.hcvguidelines.org/). ( C , I )
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Fibrosis Assessment in HCV-Infected HCT Candidates and Recipients

All HCV-infected HCT candidates should undergo assessment of the stage of liver fibrosis and the presence of cirrhosis. (CI)
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The presence of cirrhosis may affect duration and type of HCV therapy and will identify patients who need to be screened for HCC and the presence of esophageal varices. (CI)
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The decision to perform a liver biopsy should be made only after careful consideration of the risks and benefits of the procedure. (BI)
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Serologic marker panels for detection of fibrosis have not been studied in HCV-infected HCT candidates, and their use is not recommended. (CIIb)
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Ultrasound-based vibration-controlled transient elastography (FibroScan VCTE; Echosens, Paris, France) has not been studied in HCT recipients, and thus results should be interpreted with caution. (CIIb)
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When to Treat HCV Infection in Donors and Autologous or Allogeneic HCT Candidates and HCT Survivors

HCV-infected donors should be evaluated for HCV therapy and treated before cell harvest to prevent transmission of HCV to uninfected recipients, if possible. (CI)
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All HCT candidates with HCV infection should be evaluated for HCV therapy before the start of conditioning therapy; after transplant, HCV-infected survivors should also be evaluated for therapy. (BI)
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When possible, HCV-infected HCT candidates should be started on therapy and should complete therapy for HCV before transplant. (CIIa)
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After HCT, the following patients should be treated for HCV without delay: HCV-infected patients who develop fibrosing cholestatic hepatitis C, patients with cirrhosis whose condition is deteriorating, and patients who underwent HCT for HCV-related lymphoproliferative disorders. (CI)
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After HCT, treatment for HCV can be deferred until after immune reconstitution for patients not meeting the criteria above. (CI)
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All HCV-infected long-term survivors of HCT should be offered antiviral therapy. (CI)
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HCV therapy should be undertaken only with the intention of completion of the full course of therapy as defined in the AASLD-IDSA Hepatitis C Guidance (http://www.hcvguidelines.org/). Treatment interruption is not recommended. ( C , I )
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IFN-based regimens should be avoided in donors and HCT candidates/recipients with HCV infection because of their suboptimal efficacy and safety. (BI)
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HCV therapy should be undertaken by providers experienced in management of HCV in HCT recipients in close collaboration with transplant teams. (BI)
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Role of DAA Combinations in HCV-Infected HCT Recipients

Recommendations by HCV genotype as of August 2015

For infection with genotypes 1a or 1b HCV, treatment with one of the following four DAA combinations is recommended:
(1) Daily daclatasvir and sofosbuvir with or without ribavirin
(2) Daily fixed-dose combination of ledipasvir and sofosbuvir
(3) Daily fixed-dose combination of ombitasvir, paritaprevir, ritonavir, and twice-daily dasabuvir with or without ribavirin
(4) Daily sofosbuvir plus simeprevir with or without ribavirin
()
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For infection with genotype 2 HCV, the preferred regimen is sofosbuvir plus weight-based ribavirin; those who cannot tolerate ribavirin should be treated with daily daclatasvir and sofosbuvir. ()
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For infection with genotype 3 HCV, treatment with one of the following DAA combinations is recommended:
(1) Daily daclatasvir and sofosbuvir with or without ribavirin
(2) Daily sofosbuvir and ribavirin plus weekly pegylated-interferon
()
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For infection with genotype 4 HCV, treatment with one of the following the three DAA combinations is recommended:
(1) Daily fixed-dose combination of ledipasvir and sofosbuvir
(2) Daily fixed-dose combination of ombitasvir, paritaprevir, ritonavir, and ribavirin
(3) Daily sofosbuvir and ribavirin
()
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For infection with genotypes 5 or 6 HCV, the preferred regimen is daily fixed-dose combination of ledipasvir and sofosbuvir. (BIIa)
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Monotherapy with a DAA is not recommended for any patient with HCV infection. (AIII (no benefit))
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The choice of regimen should be individualized on the basis of patient-specific data, including potential drug interactions. ()
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Treatment considerations in specific patient populations

HCT recipients often receive multiple drugs that could have pharmacologic interactions with DAAs or toxic effects that overlap with those of DAAs. Treating physicians should be mindful of potential drug interactions and/or side effects, although this has not been extensively studied in HCT recipients. ()
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In patients with mild (creatinine clearance 60 to 89 mL/min) to moderate (creatinine clearance 30 to 59 mL/min) renal impairment, no dosage adjustment is required for daclatasvir, sofosbuvir plus simeprevir, ledipasvir plus sofosbuvir, or ombitasvir, paritaprevir, ritonavir, and dasabuvir. (AI)
The total daily dose of ribavirin should be reduced for patients with creatinine clearance ≤50 mL/min.
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In patients with severe renal impairment (creatinine clearance 15 to 29 mL/min) or with end-stage renal disease, safety and efficacy data for DAAs are not available; treatment can be contemplated after consultation with an expert (CIIb)
or as new data in this patient population become available. If ribavirin is used, dose should be reduced.
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Patients coinfected with HIV and HCV should be treated like HCV-monoinfected patients, except that interactions with antiretroviral medications must be recognized and managed. (BI)
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Drug–Drug Interactions in HCV-Infected HCT Candidates and Recipients Receiving DAAs and Conditioning Regimens or Immunosuppressive Agents

Recommendations for drug-drug interactions as of August 2015
Physicians should frequently assess for drug–drug interactions in HCV-infected HCT recipients. (CI)
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In patients receiving tacrolimus concomitantly with paritaprevir and ritonavir, holding tacrolimus for one day with an approximate dose reduction of 75% may be required. Due to the prolonged half-life of tacrolimus with this combination more frequent blood level assessment of tacrolimus, such as twice to thrice weekly, may be indicated. Some patients may even require intermittent dosing of tacrolimus based on blood levels. In patients receiving concomitant cyclosporine, increased therapeutic drug monitoring and an 80% decrease of the cyclosporine dose may be required. (BIIb)
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In patients receiving sirolimus concomitantly with paritaprevir and ritonavir, increased therapeutic drug monitoring and a decrease of 90% or more in the sirolimus dose may be required. (CIIb)
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Direct acting antivirals simeprevir, sofosbuvir, ledipasvir/sofosbuvir, and daclatasvir are known to have the least clinically significant interactions with commonly administered immunosuppressive medications following HCT. In patients with multiple medication interactions or those in whom it is prudent to minimize such interactions based on clinical assessment preference may be given to the aforementioned treatment regimens. (CI)
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Overlap between Toxic Effects of DAAs and of Conditioning Regimens and Symptoms of GVHD in HCV-Infected HCT Candidates and Recipients

No recommendations can be made regarding overlap between the toxic effects of DAAs and the toxic effects of HCT conditioning regimens or symptoms of GVHD because evidence is lacking. ()
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Recommendation Grading

Overview

Title

Hepatitis C Virus Infection Among Hematopoietic Cell Transplant Donors and Recipients

Authoring Organization

American Society for Transplantation and Cellular Therapy

Endorsing Organization

American Association for the Study of Liver Diseases

Publication Month/Year

August 6, 2015

Last Updated Month/Year

January 10, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Older adult

Health Care Settings

Hospital, Outpatient, Operating and recovery room

Intended Users

Clinical researcher, nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Treatment, Management, Prevention

Diseases/Conditions (MeSH)

D006526 - Hepatitis C, D018380 - Hematopoietic Stem Cell Transplantation

Keywords

hepatitis C virus, Hematopoietic Cell Transplant, antiviral therapies