Transmission of Hepatitis C Virus Through Transplanted Organs and Tissue

Kentucky and Massachusetts, 2011

Michael R. Marvin, MD; Melissa Steele; Doug Thoroughman, PhD; Tennis J. Sugg, MPH; Kraig E. Humbaugh, MD; Louise E. Vaz, MD; Sandra K Burchett, MD; Kristin Moffitt, MD; Carrie F. Nielsen, PhD; Scott D. Holmberg, MD; Jan Drobeniuc, MD; Yury Khudyakov, PhD; Matthew J. Kuehnert, MD; Susan N. Hocevar, MD

Disclosures

Morbidity and Mortality Weekly Report. 2011;60(50):1697-1700. 

In This Article

Abstract and Introduction

Introduction

On September 29, 2011, the United Network for Organ Sharing notified CDC of two patients who tested positive for hepatitis C virus (HCV) infection approximately 6 months after receiving kidney transplants from a deceased donor. Before transplantation, the donor had tested negative for HCV antibody by the organ procurement organization. Tissue also was procured from the donor for possible transplantation. The tissue bank performed an HCV antibody test on the donor's serum specimen that was negative and nucleic acid testing (NAT) that was positive, but misread as negative. Retesting of the donor specimen during the investigation confirmed the NAT results as positive. Donated tissue included 43 musculoskeletal grafts and one cardiopulmonary patch, which were distributed to health-care facilities in several states. An investigation was initiated to 1) identify potential sources of the donor's infection, 2) document the mode of transmission to the organ recipients, and 3) ensure timely notification of the implanting surgeons and testing of tissue recipients. Implantation of infected HCV tissue occurred after recognition of new HCV infection in the organ transplant recipients, highlighting the need for rapid communication between transplant centers, organ procurement organizations, tissue banks, and public health authorities regarding suspected transplantation transmission events.

Donor Investigation

The donor, a middle-aged man in Kentucky, sustained a traumatic brain injury in March 2011 in an all-terrain vehicular incident and died 2 days later. His medical history was significant for schizophrenia, substance abuse, and a 5-month incarceration approximately 10 years before his death. The donor had no known history of intravenous drug use or other hepatitis risk factors, according to his father at the time of organ procurement; however, further investigation revealed that the donor's father had limited contact with his son during the year before his death and was unfamiliar with recent personal habits or behaviors.

Policies of the Organ Procurement and Transplantation Network (OPTN), the oversight entity for solid organs in the United States, require testing for HCV by antibody only, whereas the Food and Drug Administration (FDA), which regulates human cells, tissues, and cellular and tissue-based products, requires screening of donated tissue for HCV by both antibody and NAT.[1] The donor's HCV antibody tested negative on both organ and tissue donor screening, but misreading of the reaction wells on testing led to an incorrectly reported negative HCV NAT result. Once this error was identified, repeat NAT was performed at the tissue bank and confirmed that the donor was HCV-positive at the time of donation. During the donor's final hospital stay in March, he received six units of blood products. Pretransfusion serum from the donor was not available for analysis. Testing of posttransfusion stored serum at CDC on October 28 confirmed by NAT that the donor was HCV-positive with genotype 1a and a viral load of >69,000,000 IU/mL. Blood traceback investigation of the six associated blood donors to the infected donor is ongoing, and all remaining units from these donations have been quarantined.

Organ Transplant Investigation

In March 2011, three organs (two kidneys and the liver) from the donor were transplanted into three recipients at a local hospital in Kentucky (Figure). Both kidney recipients had tested negative for hepatitis C before transplant, whereas the liver recipient had a previous diagnosis of hepatitis C.

Figure.

Investigation timeline after initial report of transmission of hepatitis C virus (HCV) from an organ and tissue donor — Kentucky and Massachusetts, 2011
Abbreviations: OPO = organ procurement organization; NAT = nucleic acid testing; UNOS = United Network for Organ Sharing.

First Kidney Recipient

On July 26, 2011, the recipient of the first kidney, a man aged 41 years, was noted to have elevated liver enzymes (aspartate aminotransferase [AST]: 161 U/L; alanine aminotransaminase [ALT]: 217 U/L). HCV antibody testing conducted August 22 was negative. Liver function tests continued to be elevated, and HCV NAT performed September 19 was positive.

Second Kidney Recipient

The recipient of the second kidney, a woman aged 46 years, was noted to have elevated liver function tests on August 25 (AST: 206 U/L, ALT: 221 U/L); HCV NAT was positive September 21.

Liver Recipient

The liver recipient, a man aged 51 years, had a history of chronic infection with HCV, genotype 1a, before transplant. Liver function testing on September 7 was unchanged from his baseline (AST: 46 U/L, ALT: 55 U/L).

At CDC, serum specimens were tested for HCV RNA. Serum collected after organ transplantation from all three recipients tested positive for HCV by NAT at CDC, and all three HCV strains were confirmed to be genotype 1a.

Tissue Transplant Investigation

On September 29, the organ procurement organization notified the tissue bank of the apparent HCV transmission to the kidney and liver recipients. The tissue bank informed health-care facilities, and a voluntary recall was begun on September 30. The tissue bank had distributed 43 musculoskeletal grafts and one cardiopulmonary patch to health-care facilities, but names and contact information for surgeons who implanted these tissues were not uniformly available at the time of recall. CDC telephone notification of all surgeons and requests for testing of all patients was completed on October 27.

The cardiopulmonary patch, the only nonmusculoskeletal tissue distributed, had been treated with antibiotics by the tissue bank according to protocol and was implanted by a health-care facility in Massachusetts on September 26. After the health-care facility was notified, the recipient underwent testing. Hepatitis C antibody was negative, but NAT was positive at 82,000 IU/mL; the recipient's ALT was normal (12 U/L).

The 43 distributed musculoskeletal grafts were treated chemically and by irradiation at the tissue bank, according to protocol. Fifteen of the musculoskeletal tissues were implanted; the remaining 28 were returned to the tissue bank. The 15 recipients of musculoskeletal tissues were recommended to receive HCV serologic testing and NAT immediately and again 6 months from the time of tissue implantation. As of December 16, initial test results from 14 of the musculoskeletal tissue recipients were known, and all were negative based on HCV NAT.

Molecular Characterization of HCV Strains

To determine the genetic relatedness among the HCV strains obtained from the donor, the two kidney recipients, the liver recipient, and the cardiopulmonary patch recipient, maximum likelihood phylogenetic trees were created.[2] These analyses showed that two specimens from the donor and the three specimens from the kidney recipients and cardiopulmonary patch recipient shared identical NS5b sequences; the liver recipient did not share these sequences, indicating previous infection. Quasispecies analysis was performed on the specimens that shared identical NS5b sequences.[3] The E1-HVR1 quasispecies sequences from the donor, the two kidney recipients, and the cardiopulmonary patch recipient clustered in a single group, indicating their close genetic relatedness consistent with a common source of HCV transmission. The donor and the two kidney recipients and one cardiopulmonary patch recipient had from two to 10 distinct E1-HVR1 sequences that shared from 99.7% to 100% similarity with each other.

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