Supplementary Material
Post-transplant immune suppression and anti-infective prophylaxis
Tacrolimus (FK) was administered to achieve a 12-hour serum trough level of 8-10
ng/mL for the first six months post-LT, 5-8 ng/mL from 6-12 months post-transplant and 3-5
ng/mL for > 12 months post-LT. LT recipients with kidney disease received FK with lower goal
trough levels (5-8 ng/mL for the first six months post-LT followed by 3-5 ng/mL beyond six
months) and mycophenolate mofetil at target dose of 1.5 to 2.0 g daily (or equivalent dosage of
mycophenolic acid). All recipients received opportunistic infection (OI) prophylaxis with
valganciclovir, trimethoprim-sulfamethoxazole, and nystatin suspension with additional
prophylaxis as indicated by plasma CD4+ T lymphocyte cell count/mm3 (CD4) or prior OI.
DAA doses
Standard doses of SOF (400 mg daily), SMV (150 mg daily), and RBV (400 mg daily
AM, 600 mg daily PM for weight ≤ 75 kg) were utilized.
Laboratory Monitoring
Plasma hepatitis C virus RNA levels were quantified using COBAS®
AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, v2.0 (Roche Diagnostics, Indianapolis,
IN; lower limit of detection (LLD) of 15 IU/mL with the exception of one EOT HCV RNA
quantification performed at an outside laboratory (LLD 43 IU/mL). HCV genotype (GT) was
determined by the VERSANT® HCV Genotype 2.0 Assay (LiPA; Siemens Medical Solutions
Diagnostics, Tarrytown, NY).
Supplementary Table 1: Specific patient characteristics prior to and during DAA therapy
Age
Gender
Race
HCV GT
Prior IFN-Tx
#38
54
Male
Hispanic
2b
Yes
#43
56
Male
White
1a
Yes
#44
39
Male
Hispanic
1aa
No
#89
44
Male
Black
1b
Yes
#93
48
Male
White
1a
No
Co-morbidities
CKD
CKD, HCCb
Obesity
CKD
CKD, DM
HIV Diagnosis
Risk for HIV/HCV
1980
IVDU
PJP,
candidiasis
184 (17)
< 20
ABC + 3TC
+ RAL
1989
Hemophilia
2004
IVDU, MSM
2007
MSM
None
None
464 (35)
<20
TDF + FTC
+ EFV
TDF + FTC
+ RAL
6/7/08
193 (35)
26
TDF + FTC
+ RAL
Prior OI
CD4 (%)d
HIV RNAe
Initial cART
Regimen
cART at DAA
Start
LT Date
LT Characteristic/
Complication
Post-LT
Infections
No change
7/29/12
Hepatic
artery
stenosis
CDI,
Influenza,
PNA, MRSA
SSTI
1993
MSM
#94
39
Male
White
1a
No
CKD, FTT,
MSOFc
1985
Hemophilia
#101
60
Male
White
1a
No
CKD, CAD,
HCCb
1985
IVDU
#110
67
Male
Hispanic
1a
No
CKD, DM,
HCCb
1994
MSM
PJP
No
MAC
None
None
405 (36)
<20
TDF + FTC
+ RAL
44 (25)
<20
ABC + 3TC
+ RAL
No change
No change
2/4/13
324 (35)
<20
ABC + 3TC
+ EFV
ABC + 3TC
+ DTG
11/26/13
12/3/11
5/29/13
360 (27)
<20
TDF + FTC
+ EFV
TDF + FTC
+ RAL
7/23/09
150 (28)
<20
TDF + 3TC
+ ATV/r
TDF + FTC
+ RAL
4/24/07
None
HCV+ donor
None
DCD graft
Living donor
graft
Re-do LT for
HAT
None
None
None
None
Thrush, CDI
E.coli
peritonitis w/
bacteremia
SSTI
None
Moderate
cellular
rejection
2008
7/25/13:
F0, A1
1,725,138
1.53
2.19
Prior Graft
Rejection
None
Mild cellular
rejection
6/24/08
Latest Liver
Biopsyf
HCV RNAg
APRI
FIB-4
3/6/13:
F0, A1
63,607,896
2.09
4.27
6/1/09:
F0, A1
3,547,068
0.73
2.62
No change
None –
(moderate
cellular
rejection,
post-DAA)
5/23/13:
F0-F1, A1
2,077,031
0.65
2.22
Mild cellular
rejection
12/4/13
None
None
Moderate
cellular
rejection
8/14/09
12/4/13:
Mild ACR
8,679,828
0.41
1.29
1/22/13:
F0
2,212,930
0.85
2.02
12/23/13:
NRH
37,508,565
8.60
16.12
4/25/12:
F2, A1
552,941
1.09
3.44
MELD
CP Score
10
N/A
11
N/A
9
N/A
12
N/A
Initial IS Regimen
FK 1 mg
AM, 0.5 mg
PM
FK 1 mg BID
FK 0.5mg
BID
FK 5mg BID,
MMF 250
mg BID
IS at DAA Start
FK 0.5 mg
BID
FK 0.5 mg
BID
Same
27
11C
14
N/A
7
N/A
Pred 2.5mg
QD, FK
0.5mg BID
FK 1.5mg
BID
FK 0.5mg q
10 days
Same
Same
Same
FK 0.5 mg
BID
No change
No change
3/26/14
SOF + SMV
1/17/14
SOF + SMV
Unable to
assess patient
intubated
DAA Start Date
DAA Regimen
FK 1 mg
AM, 0.5 mg
PM
4/15/14
SOF + RBV
3/18/14
SOF + SMV
Reported Side
Effect
Congestion,
Mild Fever
Mental
fogginess
Back pain
Headache
Fatigue
N/A
Heroin
relapse.
Graft
rejection
(after DAAs)
N/A
N/A
IS Change During
DAA
Other Adverse
Event
N/A
None
None increased
after DAA
5/21/14
SOF + SMV
FK 3 mg
BID, MMF
250 BID
FK 1 mg
BID, MMF
250 BID
9/25/14
SOF + SMV
11
N/A
FK 0.5mg
qAM, 1mg
qPM; MPA
350 BID
Death
None increased
after DAA
6/1/14
SOF + SMV
FK 1 mg BID
8/7/14
SOF + SMV
Fatigue,
peripheral
edema
None
reported
N/A
N/A
Abbreviations: DAA, direct-acting antiviral; HCV, hepatitis C virus; GT, genotype; IFN-Tx, interferon-based treatment; CKD, chronic kidney disease (GFR < 60 mL/min/1.73 m2 for ≥ 3
months); HCC, hepatocellular carcinoma; DM, type 2 diabetes mellitus; FTT, failure-to-thrive; MSOF, multi-system organ failure; CAD, coronary artery disease; HIV, human
immunodeficiency virus; IVDU, intravenous drug use; MSM, men who have sex with men; OI, opportunistic infection; PJP, pneumocystis jirovecii pneumonia; MAC, mycobacterium
avium complex; CD4, CD4+ T-lymphocyte count; cART, combined antiretroviral therapy; ABC, abacavir; 3TC, lamivudine; TDF, tenofovir; FTC, emtricitabine; RAL, raltegravir; DTG,
dolutegravir; ATV/r, ritonavir-boosted atazanavir; LT, liver transplant; DCD, donation after cardiac death; HAT, hepatic artery thrombosis; CDI, clostridium difficile infection; PNA,
pneumonia; MRSA, methicillin-resistant staphylococcus aureus; SSTI, skin or soft tissue infection; ACR, acute cellular rejection; NRH, nodular regenerative hyperplasia, APRI, AST-toplatelet ratio index; FIB-4, fibrosis-4 score; MELD, model for end-stage liver disease; CP, Child-Pugh; IS, immunosuppression; FK, tacrolimus; MMP, mycophenolate mofetil; MPA,
mycophenolic acid; pred, prednisone; SOF, sofosbuvir; RBV, ribavirin; SMV, simeprevir
a
Pre-transplant GT 3, however after LT with HCV+ liver GT 1a confirmed
b
HCC present prior to LT
c
Patient with respiratory failure requiring mechanical ventilation, liver failure, recurrent gastrointestinal bleeding, hypotension requiring vasopressor support, protein-calorie malnutrition,
extra-vascular volume overload with pleural effusions, ascites and peripheral edema
d
Measured in cells/mm3
e
Measured in copies/mL
f
Most recent liver biopsy prior to DAA initiation
g
Measured in IU/mL