Recurrence of hepatitis C following orthotopic liver transplantation: a polymerase chain reaction and histological study

Sallie, Richard; Cohen, Alexander T.; Tibbs, C. J.; Portmann, Bernard; Rayner, Anne; O’Grady, John; Tan, Kelvin Bryan; Williams, Roger

doi:10.1016/s0168-8278(94)80098-7

Cited by 40 publications

(26 citation statements)

References 19 publications

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“…4,17 In addition, patients may acquire HCV infection after OLT. [20][21][22] Histological hepatitis occurs more often in HCV RNA PCR-positive patients after OLT than in those patients who remain negative for HCV RNA by PCR. 4,[20][21][22][23][24] Although HCV RNA PCR is a sensitive and specific diagnostic method, 3,6,11 it may fail to demonstrate the presence of HCV during the early stages of recurrence.…”

Section: Discussionmentioning

confidence: 99%

Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation

et al. 1997

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Recurrent hepatitis C infection after orthotopic liver transplantation (OLT) is frequent and may occur as early as a few weeks postoperatively. Early histopathological features of recurrent hepatitis C virus (HCV) infection may be modified by immunosuppressive therapy and can be difficult to differentiate from acute allograft rejection (AAR). Thus, we retrospectively compared histopathological features of liver biopsy specimens from two carefully selected patient groups: one with unequivocal recurrent hepatitis C, the other with unequivocal AAR. Index biopsy specimens obtained at the time of the appearance of liver test abnormalities after OLT and all serial liver biopsy specimens (2 to 13 per patient) were assessed under code and scored semiquantitatively for 44 histopathological variables. The index biopsy specimens from patients with recurrent HCV infection and AAR index biopsies (AAR-Ib) differed significantly (P F .05) for 11 features (10 features were statistically associated with AAR and 1 with early recurrence of HCV infection). Statistically significant features associated with AAR included bile duct injury with overlapping nuclei, lymphocytic infiltrates and necrosis, endothelialitis, portal inflammatory infiltrates containing eosinophils and polymorphonuclear leukocytes, hepatocyte mitoses, and zone 3 canalicular cholestasis. In contrast, the only statistically significant feature associated with early recurrent HCV was sinusoidal dilatation. Stepwise discriminant analysis showed that the presence of eosinophils in the portal inflammatory infiltrate, bile duct necrosis, and bile duct lymphocytic infiltrates were independently associated with AAR. However, serial biopsy specimens from patients with recurrent HCV infection showed statistically significant progression in scores for portal inflammation, portal lymphoid aggregates, and lobular inflammation. We conclude that (1) multiple histopathological features are associated with AAR; (2) early recurrent HCV infection is characterized by elevated alanine aminotransferase levels, positive HCV RNA by polymerase chain reaction (PCR), and absence of diagnostic histopathological features; and (3) serial biopsies are needed to demonstrate progression of histopathological features of recurrent hepatitis C.

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Section: Discussionmentioning

confidence: 99%

Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation

et al. 1997

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“…Although orthotopic liver transplantation has emerged as an effective treatment for end stage chronic hepatitis C, recurrent infection of the allograft occurs almost universally according to most authors (1,2,4,5,12,(15)(16)(17)(18)(19)(20)(21)(22)(23). The major supporting evidence has been the post-OLT persistence of HCV RNA in serum, detected using the PCR technique, in nearly all cases (3,4,18,19,24).…”

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confidence: 99%

“…The major supporting evidence has been the post-OLT persistence of HCV RNA in serum, detected using the PCR technique, in nearly all cases (3,4,18,19,24). Further evidence for the nearly universal recurrence of hepatitis C has been the detection of HCV RNA in liver tissue by RT-PCR in more than 90% of cases (12,15,23).…”

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Early Detection of Hepatitis C Allograft Reinfection after Orthotopic Liver Transplantation: A Molecular and Histologic Study

et al. 2000

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After orthotopic liver transplantation (OLT), patients with chronic hepatitis C virus (HCV) infectionshow nearly universal persistence of viremia and reinfection of the liver, but identifying the point at which the liver is reinfected morphologically can be difficult. One tool that may potentially be useful to detect reinfection is reverse transcriptasepolymerase chain reaction (RT-PCR), which has proven to be highly sensitive for detecting HCV RNA in formalin-fixed paraffin-embedded liver tissue. Our purpose was to gain insight into the time frame of HCV reinfection by assaying for HCV RNA in serial posttransplant liver biopsy specimens. Our study population consisted of 14 patients who underwent liver transplantation for hepatitis C and had confirmed HCV RNA in pretransplant serum, absence of HCV RNA in donor livers, and available consecutive posttransplant liver allograft specimens. We performed RT-PCR for HCV RNA in serial posttransplant liver biopsy specimens, beginning at 1 week until at least one biopsy from each tested positive. HCV RNA was detected in liver tissue by RT-PCR in 1-week post-OLT liver samples in 6 of 14 (42.8%) patients, the earliest being 5 days post-OLT. Eventually, each of the remaining eight samples became RT-PCR positive as well; the first detections occurred in these at 3 weeks (three cases), 4 weeks (three cases), 48 weeks (one case), and 144 weeks (one case). Histologic identification of hepatitis C recurrence was relatively insensitive in relation to these molecular data. These data suggest that (1) HCV RNA reinfection is nearly universal after liver transplantation in patients with chronic hepatitis C infection, (2) molecular reinfection by HCV occurs at a variable interval post-OLT, with the majority of allograft livers reinfected as early as 1 week, and (3) morphologic features of hepatitis C are usually appreciable at the time of "molecular" recurrence.

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“…HCV RNA has been shown to persist in serum after OLT, [19][20][21] and the ability of HCV to infect the allograft is indisputable. However, the reported frequency and time frame of clinically or histologically recognized recurrent hepatitis C have varied considerably; rates have ranged from 14% to 100%, and onset has occurred as early as 4 weeks 9,22 to as late as 3 years. 23 More recent evidence indicates that hepatitis C may recur histologically in a subtle, lobular fashion as early as 1 week after OLT (unpublished data, Batts KP et al, November 1996).…”

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Reverse transcriptase-polymerase chain reaction fails to detect peripheral-blood hepatitis C RNA in formalin-fixed liver tissue

et al. 1998

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Currently, one of the major indications for liver transplantation is infection with hepatitis C virus (HCV). Many studies have suggested that recurrent infection with HCV is universal after transplantation. Fastidious techniques, such as reverse transcriptase-polymerase chain reaction (RT-PCR), have proved to be highly sensitive for detecting HCV RNA in serum and in fresh-frozen and formalin-fixed paraffin-embedded (FFPE) liver tissue. In this study, we wanted to determine whether the identification of HCV RNA in liver tissue by RT-PCR might reflect the detection of circulating HCV RNA in blood within the tissue, rather than implying true tissue infection. We performed RT-PCR for HCV RNA in FFPE liver biopsy specimens taken from 14 donor allografts shortly before and immediately after implantation into recipients. The recipients were known to have HCV RNA in serum and explanted liver tissue, as determined by RT-PCR. We were unable to detect HCV RNA in any of the study samples, either before or after transplantation. In a related study, qualitative and quantitative HCV RNA analyses were performed by RT-PCR and branched DNA (bDNA) amplification, respectively, on serum samples collected pretransplantation and immediately posttransplantation from 10 other patients who underwent transplantation for hepatitis C. HCV RNA was detected in all serum samples before and after transplantation by RT-PCR; however, the bDNA assay detected HCV RNA in only 6 of 10 samples pre-orthotopic liver transplantation (OLT) and in none of the immediately post-OLT samples. In our system, despite the RT-PCR detection of HCV RNA in serum before and after the transplantation, HCV RNA is not detectable in the peripheral blood that accompanies formalin-fixed liver tissue. This implies that RT-PCR detection of HCV RNA in tissue reflects true liver infection, rather than contamination by HCV RNA in accompanying peripheral blood.

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Recurrence of hepatitis C following orthotopic liver transplantation: a polymerase chain reaction and histological study

Cited by 40 publications

References 19 publications

Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation

Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation

Early Detection of Hepatitis C Allograft Reinfection after Orthotopic Liver Transplantation: A Molecular and Histologic Study

Reverse transcriptase-polymerase chain reaction fails to detect peripheral-blood hepatitis C RNA in formalin-fixed liver tissue

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