Quality of Life in Long-Term Liver Transplant Recipients with Hepatitis C

Catherine Rongey, W. Ray Kim, Rachel A. Pedersen, Michael Malinchoc, E. Rolland Dickson, Marlon F. Levy

 

Background

Liver transplantation (OLT) fundamentally improves quality of life (QOL) of recipients. Although hepatitis C (HCV) recurs frequently after OLT, long-term, longitudinal data about QOL of OLT recipients with HCV are not available.

 

Aims

a)     To compare longitudinally QOL in OLT recipients with HCV to those with other diagnoses

b)     To determine impact of post transplant HCV recurrence on quality of life

c)     To describe impact of quality of life on patients with long term transplant survival

 

Methods

QOL data have been collected prospectively in a multicenter database using the NIDDK-QA form, the reliability and validity of which have been established previously. Summary scores were calculated according to a published algorithm (Hepatology 2000) for each domain of the instrument, namely liver symptoms (LS, possible scores: 0-4), physical function (PF: 0-100), health satisfaction (HS: 1-7), and overall well-being (WB: 2.1-14.7). In all domains, higher scores indicate better QOL.

 

Results

The longitudinal cohort consisted of 1041 adult primary OLT recipients between 1990 and 1995 who responded to the QOL survey at OLT evaluation. These included 247 with HCV, 321 with cholestatic disease (PBC and PSC), and 473 with all other diagnoses. At baseline, QOL in HCV patients was comparable to that in other groups except for PF (mean (SD) score 27.9 (25.5) for HCV, 35.0 (26.4) for cholestatic and 31.2 (26.8) for others). In the table, at 1-2 years following OLT, patients with HCV had significantly lower QOL compared to others in all domains. However, at 5 years, these differences disappeared, especially between HCV and 'other' patients. These trends were at least in part due to the fact that HCV patients remaining in the cohort at 5 years had had a significantly better QOL at 1-2 years than those in whom 5 year data were not available (dead or lost to follow-up), including PF (70.1 vs 55.9, p<0.01), HS (5.5 vs 5.0, p=0.01) and WB (11.8 vs 10.9, p=0.02) domains.

 

Conclusions

At 1-2 years post OLT, recipients with HCV have QOL demonstrably inferior to those with other diagnoses. However, longer term data suggest that HCV patients who survive without succumbing to recurrent disease do maintain good QOL.

 

The authors also noted:

a)     Patients with HCV that were transplanted had the lowest survival rate

b)     HCV Patients reported consistently lower physical functioning after transplantation, but no significant difference over time

c)     HCV patients that survive long term transplant maintain a good quality of live

 

Time since OLT 

 

HCV 

Cholestatic 

Other 

p* 

1-2 yrs 

Respondents 

154 (78%) 

259 (90%) 

319 (86%) 

 

 

LS 

2.8 (0.7) 

3.1 (0.6) 

3.1 (0.6) 

<0.01 

 

PF 

60.4 (29.5) 

68.8 (27.1) 

66.2 (28.1) 

0.03 

 

HS 

5.1 (1.2) 

5.3 (1.1) 

5.4 (1.2) 

0.04 

 

WB 

11.2 (2.2) 

11.8 (2.1) 

11.7 (2.1) 

0.01 

5 yrs 

Respondents 

53 (98%) 

104 (82%) 

97 (76%) 

 

 

LS 

2.9 (0.7) 

3.1 (0.6) 

3.0 (0.7) 

0.12 

 

PF 

64.2 (30.2) 

70.2 (25.5) 

69.6 (27.7) 

0.07 

 

HS 

5.1 (1.4) 

5.2 (1.1) 

5.0 (1.1) 

0.6 

 

WB 

11.2 (2.2) 

11.8 (1.8) 

11.3 (2.0) 

0.09 

Data are shown as mean (SD) except for respondents (%response). * by the Kruskal Wallis test

 

Effect of Hepatitis C (Hep C) and Type 2 Diabetes (DM) on Patient and Graft Survival in Patients with Solitary Liver, Combined and Serial Liver-Kidney Transplants

Jasmohan S. Bajaj, Maureen A. McBride, Katarina Anderson, Kia Saeian

 

Introduction

Improvements in post-transplant management have led to an increasing number of multiple organ transplants, including combined liver and kidney transplants. As Hep C and DM are leading causes for liver and kidney transplantation in the U.S. respectively, their impact on combined or serial liver-kidney transplants could have important implications for organ allocation.

 

Aim

Determine if pt and graft outcomes in pts with either combined or serial liver and kidney transplantation are affected by Hep C or DM status.

 

Methods

The UNOS database was queried for all primary cadaveric adult liver-alone, serial liver and cadaveric or living donor kidney, and combined cadaveric liver-kidney transplants between 1988 and 2001 to provide follow-up of at least 2 years. Kaplan-Meier methods were used to calculate graft and patient survival rates and Hep C and DM status were analyzed.

 

Results

Liver transplants (n) : Hep C 8868, no Hep C 27534; DM 3876, no DM 19864. Combined transplants (n): Hep C 181, no Hep C 522; DM 201, no DM 324. Serial transplants (n): Hep C 124, no Hep C 479; DM 121, no DM 362. In Hep C pts with liver transplant, there was decreased pt survival (p<0.0001) and graft survival (p<0.0001) as compared to others (Table). Hep C was also associated with decreased pt survival (p=0.03)and graft survival (p=0.001) in serial transplants as compared to combined transplants. In liver transplant pts, both pt (p<0.0001) and graft survival (p<0.0001) were significantly decreased in pts with DM as compared to those without DM. DM did not significantly affect outcomes in serial or combined transplants.

 

Conclusions

  1. Hep C is associated with lower pt and liver graft survival
  2. In Hep C patients, combined liver-kidney transplant pts have better outcomes compared to serial transplants; combined instead of serial transplants should be considered in Hep C,
  3. DM is associated with decreased pt and liver graft survival in solitary liver transplants but does not affect outcomes in serial or combined liver-kidney transplants.
  4. Since HCV may be a factor for DM that it is not surprising that DM would be more prevalent post-transplant.

 

(All in %) 

5 yr pt survival 

5 yr liver graft survival 

5 yr pt survival 

5 yr liver graft survival 

 

Hep C  

Other 

Hep C  

Other 

DM  

Other 

DM 

Other 

Liver Alone 

70† 

73.2† 

62.3* 

70* 

67 ‡ 

74‡ 

61^ 

68^ 

Combined 

69.2 

66 

66.1 

60.9 

58.7 

71.4 

54 

67 

Serial 

54.2 

66.5 

57.5@ 

74@ 

66.6 

60 

81.2 

68.2 

† , * ,¶, @ ,^,‡; significant

 

 

Influenza Vaccination in Orthotopic Liver Transplant Recipients: Efficacy and Absence of ALT Elevation

Adeyemi Lawal, Chris Basler, Andrea Branch, Julio Gutierrez, Myron Schwartz, Thomas D. Schiano

 

Introduction

Influenza vaccination has reduced the morbidity from influenza viral infection in cirrhotic patients and post liver transplant recipients. Hepatitis C (HCV) expresses an epitope that cross-reacts with an epitope expressed by influenza A virus (H1N1). The influenza A virus epitope is recognized by HLA A2-restricted cytotoxic T cells. There is a theoretical concern that influenza vaccination of HCV patients might cause aminotransferase flares by stimulating memory cells that recognize both viruses or by stimulating a non-specific inflammatory response.

 

Aim

We evaluated the efficacy of influenza vaccination in liver transplant patients and whether there were demonstrable changes in alanine aminotransferase (ALT) values post immunization.

 

Methods

Liver transplant recipients (n=51) consisting of 25 HCV (+) and 26 HCV (-) subjects were prospectively administered a standard dose of the 2002-2003 inactivated trivalent influenza vaccine. ALT values were measured at baseline, one week and 4-6 weeks post-vaccination. Antibody responses to each component of the vaccine were measured at baseline and after 4-6 weeks by hemagglutination inhibition (HAI)assays. Serologic response was defined as HAI titers ³40 or a 4-fold increase in antibody titers from baseline. An ALT elevation was defined as a rise of ≥50% or more in ALT level from baseline.

 

Results

The mean age of the patients and time from transplantation in HCV(+)and HCV(-) subjects were similar. There was no difference in the median ALT value from baseline between both groups of responders and non-responders to the H1N1 subtype of the influenza virus vaccine. A significant number of HCV (+) and HCV (-) subjects achieved adequate protective antibody titers post vaccination (P value < 0.0001). The number of subjects with adequate response to the H1, H3 and B strains at less than 4 months post transplantation were 1/7(14%), 3/7(43%) and 1/7(14%). At 4-12 months post transplant, 6/9 (67%), 8/9 (89%) and 5/9 (56%), and after 12months, 30/35 (86%), 23/35 (66%) and 16/35 (46%) responded adequately. One of two HCV (-) recipients who received the vaccination within 3 months of transplantation developed acute cellular rejection.

 

Conclusions

Influenza vaccination is not associated with ALT flares in liver transplant recipients whether or not they are infected with HCV. Although the optimal time of influenza vaccination in liver transplant recipients has not been defined, it is probably better to vaccinate patients greater than 4 months post transplantation.

 

The authors also noted:

a)     Their research indicates that Influenza vaccination is not associated with allograft rejection

b)     The study was a small study and larger studies are needed to confirm results.

c)     Generally, influenza vaccination in post transplant patients achieved protective antibody stage if given four months or longer after transplantation, but the optimal time to vaccinate would be prior to transplantation.

 

What is the Anticipated Half-Life of a Liver Allograft?

Alastair D. Smith, Carlos E. Marroquin, Erick B. Edwards, Janet E. Tuttle-Newhall, Bradley H. Collins, Dev M. Desai, Paul C. Kuo

 

Purpose

What are the relative benefits of orthotopic liver transplantation (OLT) in the face of concomitant diseases that may confer shorter patient survival than could be anticipated from the graft? Patient and liver allograft survival, by transplant indication, are unknown, but this information would further inform appropriate allocation of this precious and scarce resource. The purpose of this study was to determine liver allograft and patient half-lives.

 

Patients and methods

The United Network for Organ Sharing scientific registry was reviewed between January 1st 1988 and December 31st 1996 for all orthotopic liver transplants. The estimated half-life for liver allografts, defined as the time point at which 50% of grafts in a cohort of transplanted patients had failed, was calculated using Kaplan-Meier analysis. Estimated allograft half-lives were stratified by diagnosis, and first or subsequent transplant. Patient half-life, defined as the time point at which 50% of patients in a transplanted cohort were dead, was calculated also.

 

Results

  1. During the study period 19,717 liver allografts were transplanted (17,052 to adults).
  2. By etiology of end-stage liver disease (ESLD) patients transplanted for autoimmune hepatitis (AIH), either primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC), chronic ethanolic liver disease (ELD) and chronic hepatitis C virus (HCV) liver disease had graft half-lives of 13.4 years, 12.6 years, 9.2 and 9.1 years, respectively. Patients transplanted for other diagnoses had a graft half-life of 11.2 years.
  3. Irrespective of ESLD etiology, there was a marked difference between allograft half-lives for patients undergoing primary transplant (12 years), and subsequent transplants (1.5 years).
  4. Patient half-lives for patients transplanted for AIH, chronic ELD and chronic HCV liver disease were 14.8, 11.1 and 12.8 years respectively.

 

Conclusions

Patients with immune forms of chronic liver disease had the longest graft and patient half-lives, suggesting that this patient group has most to gain from OLT, particularly when compared with patients undergoing OLT for chronic HCV liver disease. The very short graft half-life for patients receiving a second or subsequent allograft suggests that re-transplantation should be reserved for patients with excellent functional status only.