Recurrent hepatitis C after liver transplant

Table 1 Treatment of hepatitis C virus cirrhosis with interferon and ribavirin

Ref	n	Child score	Treatment	Mean treatment duration (mo)	End of treatment response/post-LT SVR
Everson et al[1]	124	7	IFN and RBV	6-12	46%/30%
Carrion et al[2]	51	88% A or B	PEG-IFN and RBV	3	29%/20%
Everson et al[3]	63	7	PEG-IFN and RBV	4	59%/25%

LT: Liver transplantation; PEG-IFN: Pegylated-interferon; RBV: Ribavirin; IFN: Interferon; SVR: Sustained viral response rate.

Table 2 Treatment of hepatitis C cirrhosis with triple therapy

Fibrosis stage	Drug	Prior PEG-IFN responsiveness (n)	Treatment response	Serious adverse events1	Ref.
Cirrhosis	Telaprevir	21	62% SVR	9%	[4]
Bridging fibrosis and cirrhosis	Boceprevir	76	47% SVR	12%	[5]
		Relapse (n = 119)	85% SVR
		Partial response (n = 50)	42% SVR
		Null response (n = 88)	24% SVR
Bridging fibrosis and cirrhosis	Boceprevir	Relapse and partial response (n = 63)	56% SVR	12%	[7]
Child A	Telaprevir	285	67% (16 wk)	45%	[8]
	Boceprevir	204	58% (16 wk)	33%

¹Serious adverse event rate for entire study population, % of patients with undetectable hepatitis C virus RNA at 16 wk following drug initiation, an interim analysis. PEG-IFN: Pegylated-interferon; SVR: Sustained viral response rate.

Table 3 Risk factors studied for association with more severe hepatitis C virus recurrence

Factor	Evidence
Donor
Age > 40 yr	↑↑↑
Living donor	↔
Split liver	↔
DCD	↔
HCV+	↔
Macrovesicular steatosis > 30%	↑↓
IRI	↑↓
IL28B “CC” genotype	↑↓
Virus
HCV genotype 1	↑
High pre-transplant HCV RNA	↑
HCV RNA 4 mo post LT ≥ 1 × 109 mEq/mL	↑↑
CMV viremia	↑↑↑
HIV coinfection	↑↑
Recipient
Female sex	↑↑
African American D/R mismatch	↑↑
African American D/R match	↔
Metabolic syndrome1	↑
IL28B non-“CC” genotype	↑
Immunosuppression
Pulsed corticosteroids for American College of Rheumatology	↑↑↑
Tacrolimus (vs CsA)	↑↓
Sirolimus	↑
Thymoglobulin	↔
Basiliximab	↔
OKT3	↑

¹Metabolic syndrome defined by ATP-III criteria 1 yr post liver transplantation (LT)[37], homeostasis model assessment-estimated insulin resistance > 2.5 4 mo post LT[46], or hepatic steatosis ≥ 5% on an index liver allograft biopsy 1 yr post-LT[47]. ↑: Evidence of increased risk; ↔: Evidence of no increased risk; ↑↓: Indeterminate risk; DCD: Donation after cardiac death; HCV: Hepatitis C virus; CMV: Cytomegalovirus; HIV: Human immunodeficiency virus; CsA: Cyclosporin A; OKT3: Muromonab-CD3; IRI: Ischemia reperfusion injury.

Table 4 Liver biopsy findings in recurrent hepatitis C and acute cellular rejection

Favors hepatitis C	Favors rejection
Apoptotic (Councilman) bodies	Central venulitis
Lymphoid aggregates	Perivenular necrosis
Kupffer cell hypertrophy	Inflammatory bile duct damage
Mononuclear portal inflammation	Biliary epithelial senescence changes
Ballooning degeneration