METHODS OF TREATING HEPATITIS C VIRUS INFECTION
The present invention provides methods of treating hepatitis C virus (HCV) infection; methods of reducing the incidence of complications associated with HCV and cirrhosis of the liver; and methods of reducing viral load, or reducing the time to viral clearance, or reducing morbidity or mortality in the clinical outcomes, in patients suffering from HCV infection. Also provided are methods of treating liver steatosis and liver fibrosis.
1 . A method of treating a hepatitis C virus infection in an individual, the method comprising administering to the individual an effective amount of an active agent that reduces the level and/or activity of a lipid synthesis acyltransferase.
2 . The method of claim 1 , wherein the lipid synthesis acyltransferase is a diacylglycerol acyltransferase-1 (DGAT1) polypeptide, wherein said DGAT1 polypeptide comprises an amino acid sequence having at least about 75% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:1.
3 . The method of claim 1 , wherein the lipid synthesis acyltransferase is a diacylglycerol acyltransferase-1 (DGAT2) polypeptide, wherein said DGAT2 polypeptide comprises an amino acid sequence having at least about 75% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:2.
4 . The method of claim 1 , wherein the lipid synthesis acyltransferase is an acyl-CoA:cholesterol acyltransferase-1 (ACAT1) polypeptide, wherein said ACAT1 polypeptide comprises an amino acid sequence having at least about 75% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:3.
5 . The method of claim 1 , wherein the lipid synthesis acyltransferase is an acyl-CoA:cholesterol acyltransferase-2 (ACAT2) polypeptide, wherein said ACAT2 polypeptide comprises an amino acid sequence having at least about 75% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:4.
6 . The method of claim 1 , wherein the active agent is a small molecule inhibitor of a lipid synthesis acyltransferase.
7 . The method of claim 1 , wherein the active agent is an interfering RNA that specifically reduces the level of a lipid synthesis acyltransferase in a cell.
8 . The method of claim 1 , wherein the active agent is an antibody that specifically binds a lipid synthesis acyltransferase.
9 . The method of claim 1 , wherein the active agent is administered in an amount effective to reduce HCV viral titers to fewer than about 5000 genome copies/mL serum.
10 . The method of claim 1 , wherein a sustained viral response is achieved.
11 . The method of claim 1 , wherein the method further comprises administering to the individual an effective amount of a nucleoside analog.
12 . The method of claim 11 , wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, an L-nucleoside, and isatoribine.
13 . The method of claim 1 , wherein the method further comprises administering to the individual an effective amount of an interferon-alpha (IFN-α).
14 . The method of claim 13 , wherein the IFN-α is monoPEG (30 kD, linear)-ylated consensus IFN-α.
15 . The method of claim 13 , wherein the IFN-α is INFERGEN consensus IFN-α.
16 . The method of claim 13 , wherein the IFN-α is PEGASYS™ PEGylated IFN-α2a or PEG-INTRON™ PEGylated IFN-α2b.
17 . The method of claim 1 , further comprising administering to the individual an NS3 protease inhibitor, an NS5B polymerase inhibitor, or an NS3 helicase inhibitor.
18 . The method of claim 1 , wherein the HCV is genotype 1b.
19 . The method of claim 1 , wherein said administering is by subcutaneous injection or intramuscular injection.
20 . The method of claim 1 , wherein said administering is by oral delivery.