1. Volume 154, Issue 3, Pages 652-662.e8 (February 2018)
Efficacy of NVR 3-778, Alone and In Combination With Pegylated Interferon, vs Entecavir In uPA/SCID Mice With Humanized Livers and HBV Infection 
Klaus Klumpp, Takashi Shimada, Lena Allweiss, Tassilo Volz, Marc Lütgehetmann, George Hartman, Osvaldo A. Flores, Angela M. Lam, Maura Dandri 
Gastroenterology 
Volume 154, Issue 3, Pages e8 (February 2018)
DOI: /j.gastro
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2. Figure 1
On treatment change of serum HBV DNA, HBsAg, HBeAg, and serum HBV RNA. Data from Study 2, PBR-HI14–007. (A) Study design scheme; (B–E) mean values and standard deviation error bars are shown. HBV RNA data points are single points from pooled serum samples for each treatment group. NVR3-778NVR3-778A shaded area indicates the limit of quantification. Significant differences in response between the NVR3-778 + peg-IFN combo and the individual NVR3-778 and peg-IFN groups were observed in serum HBV DNA reduction and are shown for the analyses on days 28 and 42 (**P < .01). Significant differences in response between peg-IFN containing groups and vehicle group were observed in serum HBsAg and HBeAg and are shown for the analyses on day 42 (*P < .05).
Gastroenterology  , e8DOI: ( /j.gastro )
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3. Figure 2
On treatment change of intrahepatic HBV rcDNA, cccDNA, pgRNA, and total HBV RNA. Data from Study 2, PBR-HI14–007. Analysis was after 42 days of treatment. One of the mice in the NVR3-778 group was euthanized after 18 days of treatment. (A) HBV rcDNA or (B) cccDNA copies were determined by quantitative reverse-transcription PCR and normalized to the number of human hepatocytes, based on the quantification of human β-globin DNA, or (C) rcDNA copies were normalized relative to cccDNA. The expression of (D) HBV pgRNA and (E) total HBV RNA was normalized to human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA. Each dot represents a single mouse (mean measurement from 2 extractions per mouse liver). Horizontal lines depict the mean. Statistically significant differences between groups are shown (*P < .05).
Gastroenterology  , e8DOI: ( /j.gastro )
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4. Figure 3
Immunohistochemical staining of HBV-infected humanized mouse liver. Liver samples from Study 2, PBR-HI14–007. (A) HBcAg staining; (B) human cytokeratin 18 (CK18) staining indicating human hepatocytes in the chimeric liver of the humanized mice and caspase 3 staining as apoptosis marker. White arrows highlight the sporadic cells that are positive for caspase 3 staining.
Gastroenterology  , e8DOI: ( /j.gastro )
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5. Figure 4
mRNA expression levels of (A) ER stress and hepatocyte injury markers and (B) cytoplasmic DNA and RNA sensors are not affected by NVR3-778 treatment. Data from Study 2, PBR-HI Graphs show relative expression levels of the indicated genes as compared with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA. PHLDA3 (pleckstrin homology-like domain, family A), HSPA5 (heat shock 70 kD protein 5, GRP-78, BIP), DDIT3 (DNA damage induced transcript 3, CEBPZ, GADD153, CHOP), Caspase 1 (ICE, P45). DAI (Z-DNA binding protein 1, DLM-1), IFI16 (IFN-gamma inducible protein 16, IFNGIP1), RIG-I (DEAD Box Helicase 58, DDX58), PKR (protein kinase RNA-activated, EIF2AK1, p68 kinase). Statistically significant differences between groups are shown (*P < .05; **P < .01).
Gastroenterology  , e8DOI: ( /j.gastro )
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