Table 1.

Select Studies of Liver Sampling for Understanding Intrahepatic Pharmacology

Study	Study Participants	Treatment	Hepatic Sampling Technique	Sampling Analysis
Talal et al. 20144	15 genotype 1a/b chronic HCV-infected patients; cirrhotics excluded	TVR 750 mg every 8 hours, PEG-IFN and RBV for 12 weeks followed by an additional 12 of weeks of PEG-IFN and RBV	Liver FNAs were performed at baseline prior to treatment initiation, at 10 hours after treatment initiation, on days 4 and 15, and in most subjects at week 8	Intrahepatic and plasma TVR concentrations, HCV RNA, TVR resistance, viral clonal sequence analysis and microarray analysis of liver genes
Zeremski et al. 201531				Intrahepatic and peripheral CXCL10 (IP-10) protein levels
Wright et al. 20155	3 genotype 1 chronic HCV-infected non-responders to PEG-IFN and RBV; cirrhosis excluded	VNV 600 mg twice daily on days 1 – 3 and VNV 600 mg single-dose on day 4. After a minimum of 30 days washout, patients received VNV 300 mg twice daily on days 1 – 3 and 300 mg single-dose on day 4.	On study day 4 of each period, CNBs were performed 6 hours post-dose in one patient and 12 hours post-dose in the other two patients for measurement of intrahepatic VNV concentrations	Intrahepatic and plasma VNV concentrations
Lejnine et al. 201537	17 genotype 1 chronic HCV-infected patients with mild/moderate to advanced fibrosis; cirrhotics excluded.	None	FNAs and CNBs were performed at a single visit, 7 days later an additional FNA procedure was performed	Gene expression profiling via microarray and pathway analyses
	4 separate dog experiments		FNA and liver punches	Gene expression profiling via microarray for cross-species validation of human methods
Talal et al. 20124	20 patients with chronic liver disease and stage 1–3 fibrosis	Simtuzumab three infusions at 10 mg/kg or 3 mg/kg 2 weeks apart; twelve patients received an additional 24 weeks of dosing (700 mg every 2 weeks)	Liver FNAs performed prior to the first simtuzumab infusion (at week 4) and 2 weeks after the final infusion (week 10)	Intrahepatic mRNA for microarray analysis of genes associated with liver fibrosis

CNB = core needle biopsy; CXCL10 = C-X-C motif chemokine 10; FNA = fine needle aspiration; HCV = hepatitis C virus; IP-10 = interferon-gamma inducible protein-10; PEG-IFN = pegylated-interferon; ribavirin = RBV; TVR = telaprevir; VNV = vaniprevir