Treatment of Chronic Delta Hepatitis With Lonafarnib and Ritonavir

- INCLUSION CRITERIA:

1. Age 18 years or above, male or female.

2. Serum alanine or aspartate aminotransferase (ALT or AST) activities above the upper limit of normal (ALT greater than or equal to 20 or AST greater than or equal to 20 U/L in females and ALT greater than or equal to 30 or AST greater than or equal to 30 U/L in males) on an average of three determinations taken during the previous 6 months at the NIH clinical center. The mean of the three determinations will be defined as baseline levels.

3. Presence of anti-HDV in serum.

4. Presence of quantifiable HDV RNA in serum.

EXCLUSION CRITERIA:

1. Decompensated liver disease, defined by bilirubin >4mg/dL, albumin <3.0 gm/dL, prothrombin time >2 sec prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy. Laboratory abnormalities that are not thought to be due to liver disease may not necessarily require exclusion. Patients with ALT levels greater than 1000 U/L (>25 times ULN) will not be enrolled but may be followed until three determinations are below this level.

2. Pregnancy, active breast-feeding, or inability to practice adequate contraception, in women of childbearing potential or in spouses of such women. Adequate contraception is defined as vasectomy in men, tubal ligation in women, or use of two barrier methods such as condoms and spermicide combination, birth control pills, an intrauterine device, Depo-Provera, or Norplant. In total, the participant and their partner must utilize two forms of contraception and one method must include a barrier method.

3. Significant systemic or major illnesses other than liver disease, including, but not limited to, congestive heart failure, renal failure (eGFR <50 ml/min), organ transplantation, serious psychiatric disease or depression (only if felt to be at high risk by the NIH psychiatric consultation service), and active coronary artery disease.

4. Systemic immunosuppressive therapy within the previous 2 months.

5. Evidence of another form of liver disease in addition to viral hepatitis (for example autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson disease, alcoholic liver disease, nonalcoholic steatohepatitis (but not steatosis), hemochromatosis, or alpha-1-antitrypsin deficiency).

6. Active substance abuse, such as alcohol, inhaled or injection drugs within the previous year.

7. Evidence of hepatocellular carcinoma.

8. Evidence of concurrent hepatitis C infection with positive serum hepatitis c virus (HCV) RNA.

9. Any experimental therapy or pegylated interferon therapy within 6 months prior to enrollment.

10. Diagnosis of malignancy in the five years prior to the enrollment with exception granted to superficial dermatologic malignancies.

11. Evidence of HIV co-infection; HIV 1/2 viral RNA or antigen on serum testing.

12. Concurrent usage of statins as these drugs inhibits mevalonate synthesis, which reduces protein prenylation.

13. Concurrent usage of moderate and strong cytochrome p450, family 3, subfamily A (CYP3A) inhibitors and inducers.

14. Use of any prescription, nonprescription or natural medicine (herbal) medications unless the use of medication is medically necessary with appropriate monitoring.

15. Concurrent usage of alpha 1 adrenoreceptor antagonist, antiarrhythmic, pimozide, sildenafil, sedative and hypnotics, ergot and St. John s Wort due to possible effect of ritonavir on hepatic metabolism of these drugs resulting in potentially life threatening side effects.

16. Clinically significant baseline EKG abnormalities.

17. Uncontrolled elevated triglycerides.

18. History of pancreatitis as a result of hypertriglyceridemia.

19. Inability to understand or sign informed consent.

20. Any other condition, which in the opinion of the investigators would impede the patient s participation or compliance in the study.