Lonafarnib Boosted With Ritonavir With and Without Peginterferon Alfa-2a (PEG IFN-a) in HDV (LOWR-2)

Inclusion Criteria: * Males or females, 18 to 65 years of age who are diagnosed with HDV by PCR * Chronic hepatitis D infection, genotype 1, documented by a positive anti-HDV Ab test at least of 6 months duration and detectable HDV RNA by PCR within 3 months to study entry * Liver biopsy within the last two years (biopsy can be done at the Screening Visit) * Positive viral load of \>100,000 copies/mL as measured by quantitative PCR * Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality and a QT/QTc interval \<450 milliseconds - using Bazett's correction * Females of childbearing potential (intact uterus and within 1 year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, these subjects should agree to use one of the following acceptable birth control methods throughout the study: 1. abstinence 2. surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six months minimum 3. IUD in place for at least six months 4. barrier methods (condom or diaphragm) with spermicide 5. surgical sterilization of the partner (vasectomy for six months) 6. hormonal contraceptives for at least three months prior to the first dose of study drug * Willing and able to comply with study procedures and provide written informed consent Exclusion Criteria: * Participation in a clinical trial with or use of any investigational agent within 30 days of Study Visit 1 * Patients co-infected with HIV * Patients with screening tests positive for HCV, or anti-HIV Ab * History of decompensated cirrhosis within the past year * Active jaundice defined by total bilirubin \> 2.0 excluding Gilbert's disease * INR ≥ 1.5 * Eating disorder or alcohol abuse within the past 2 years, excessive alcohol intake (\> 20 g per day for females (1.5 standard alcohol drinks) or \> 30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) (1.0 fluid oz (US) = 29.57 mL) * Drug abuse within the last six months with the exception of cannabinoids and their derivatives * Patients with absolute neutrophil count (ANC) \< 1500 cells/mm\^3; platelet count \< 100,000 cells/mm\^3; hemoglobin \< 12 g/dL for women and \< 13 g/dL for men; abnormal TSH,T4, or T3 or thyroid function not adequately controlled; or serum creatinine concentration ≥ 1.5 times upper limit of normal (ULN) * History or clinical evidence of any of the following: 1. variceal bleeding, ascites, hepatic encephalopathy, CTP score \> 6, decompensated liver disease or any other form of non-viral hepatitis 2. immunologically mediated disease (e.g., rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) requiring more than intermittent nonsteroidal anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids (inhaled asthma medications are allowed) 3. any malignancy within 3 years except for basal cell skin cancer 4. significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia) 5. chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment 6. severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization 2 * Patients with a body mass index \> 30 kg/m\^2 * Concomitant drugs known to prolong the QT interval