Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Table 1 Summary of outcomes post orthotopic liver transplant in hepatitis C virus/human immunodeficiency virus co-infection

Ref.1	Study period	Country	Patients	Median follow-up (mo)	Survival	Graft survival
Terrault et al[2]	2003-2010	United States	89	32	76% 1 yr	72% 1 yr
					60% 3 yr	53% 3 yr
Miro et al[41]	2002-2006	Spain	84	44	88% 1 yr	NR
					62% 3 yr
					54% 5 yr
Duclos-Vallée et al[43]	1999-2005	France	35	44	82% 1 yr	NR
					73% 2 yr
					51% 5 yr
De Vera et al[44]	1997-2005	United States	27	27	67% 1 yr	63% 1 yr
					56% 3 yr	52% 3 yr
					33% 5 yr	31% 5 yr
Ragni et al[94]	1997-2001	United States	15	17	80% 1 yr	NR
					57% 3 yr
					36% 5 yr
Vennarecci et al[95]	2002-2006	Italy	11	26	83% 1 yr	NR
					58% 3 yr2
Anadol et al[96]	1997-2011	Germany	19	613	58% 5 yr	NR

¹Studies with ≥ 10 patients;

²Survival reported for cohort of 12, including one hepatitis B virus/human immunodeficiency virus co-infected patient;

³For all patients. NR: Not reported.

Table 2 Summary of outcomes post orthotopic liver transplant in hepatitis B virus/human immunodeficiency virus co-infection

Ref.	Study period	Country	n	Median follow-up (mo)	Survival	Graft survival	Comments
Coffin et al[49]	2001-2007	United States	22	42	85% 1 yr	85% 1 yr	About 50% had detectable HBV pre transplant
					85% 3 yr	85% 3 yr
Tateo et al[97]	1999-2007	France	13	32	100%	100%	1 co-infected with HDV, 2 with HCV, 4 with HCV and HDV
Anadol et al[96]	1997-2011	Germany	10	611	90% 1 yr	NR
					80% 5 yr
Schreibman et al[98]	1999-2006	United States	8	NR	75% 1 yr	NR	2 co-infected with HCV, 1 fulminant hepatic failure
					75% 3 yr
Norris et al[99]	1995-2003	United Kingdom	4	22	100% 1 yr	NR

¹For entire series. HBV: Hepatitis B virus; HCV: Hepatitis C virus; NR: Not reported; HDV: Hepatitis D virus.

Table 3 Contraindications to liver transplantation in human immunodeficiency virus positive patient

Condition	Comment
Progressive multifocal leukoencephalopathy
Cryptosporidiosis	Chronic intestinal > 1 mo duration
Lymphoma	Primary CNS
Visceral Kaposi’s sarcoma	Cutaneous KS considered if remission with immune reconstitution and no active/vascular residual cutaneous lesions on physical exam and chest CT scan
Encephalopathy, HIV-related	Unless diagnosed prior to HAART and resolved on HAART with marked improvement in mental status and increased CD4+ T-cell count and no evidence of progression of CNS disease and are otherwise considered eligible from a functional standpoint

HIV: Human immunodeficiency virus; CNS: Central nervous system; CT: Computerized tomography; KS: Kaposi’s sarcoma; HAART: Highly active anti retroviral therapy.

Table 4 Drug-drug interactions: Antiretrovirals and immunosuppressants[54,102]

	Steroids	Calcineurin inhibitors (cyclosporine/tacrolimus)	mTOR inhibitors (sirolimus, everolimus)	Antimetabolites (mycofenylate mofitl)
PI	Significant increase	Significant increase in immunosuppression levels in general. Calcineurin inhibitor levels may increase or decrease with exposure to either amprenavir or fosamprenavir	Significant increase in immunosuppression levels	Generally no effect; levels may decrease with nelfinavir, lopinavir/ritonavir
NNRTI	Mild decrease in level	Mild decrease in level	Mild decrease in level	No effect on immunosuppressant levels. May decrease nevirapine levels
NRTI	No effect	No effect	No effect	May be increased with zidovudine
Integrase inhibitors	No effect	Increased with elvitegravir	Increased with elvitegravir	Increased with elvitegravir
CCR5-agonists	No effect
Fusion inhibitors	No effect

PI: Protease inhibitor; mTOR: Mammalian target of rapamycin; NNRTI: Non-nucleoside reverse transcriptase inhibitors; NRTI: Nucleoside reverse transcriptase inhibitors; CCR5: Chemokine receptor type.

Table 5 Post transplant prophylaxis

Post transplant prophylaxis	Comment
PJP prophylaxis	Trimethoprim/sulfamethoxazole SS one tablet daily life long
	Alternatives: Dapsone 100 mg daily, pentamidine 300 mg inhaled or iv monthly or atovaquone 1500 mg daily[54]
CMV	Valganciclovir 900 mg daily1; oral (1 g tid) or iv (5 mg/kg daily) ganciclovir for 3 mo in D+/R-; prophylaxis or pre-emptive monitoring and therapy in R+
Fungal	High risk patients2 should receive Fluconazole 400 mg po daily × 14 d minimum[100]
HBV (in HBV co-infected patients)	Life long HBIG targeting 100 IU/L plus either tenofovir or entecavir

¹Valganciclovir is not FDA approved for use in liver transplantation; many centers use this agent off label[101];

²High risk features include repeat or prolonged surgery, high transfusion requirements, renal failure, colonization with Candida or Choledochojejunostomy[100]. PJP: Pneumocystis jeroveci pneumonia; SS: Single strength; CMV: Cytomegalovirus; HBV: Hepatitis B virus; HBIG: Hepatitis B immunoglobulin; FDA: United States Food and Drug Administration.