Peginterferon Lambda and Lonafarnib Boosted With Ritonavir 48-Week Combination Therapy for Delta Hepatitis

* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Male or female, \>=18 years of age. * Presence of HDV RNA in serum at two points at least one day apart with HDV RNA levels that are quantifiable and above the lower limit of quantification (LLOQ) of the HDV RNA assay. * Ongoing use of either tenofovir (TDF or TAF) or Entecavir for viral suppression of HBV for at least 12 weeks with documented suppression of HBV DNA (\<100 IU/ml). EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Decompensated liver disease, defined by either bilirubin \>2mg/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 an absolute neutrophil count \<1000/dL and platelets \<75,000/dL will be excluded from the study as well. * Pregnancy or lactation. * For females of reproductive potential: Lack of use of highly effective contraception defined as tubal ligation in women, or use of two contraceptive methods such as condoms (male partner) and spermicide in combination with an intrauterine device or a progestin-based hormonal contraception (implant or injection) for at least 3 months prior to treatment until 24 weeks after end of study medication administration. Female participants with childbearing potential must not use oral birth control pills as a form of contraception due to concern for interaction with study medications leading to contraception failure. * For males of reproductive potential: Unable or unwilling to use condoms consistently in addition to female partner using another adequate contraceptive method to ensure effective contraception with partner during study participation and for an additional 24 weeks after the end of study medication administration. Patients who have undergone surgical sterilization (vasectomy) will still require female partner to utilize an additional adequate contraception method. * Inability to take oral and subcutaneous medications * Unwilling to adhere to the study intervention regimen or to comply with study procedures, or unavailability for the duration of the study * 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), or active coronary artery disease. * Systemic immunosuppressive therapy within the previous 2 months before enrollment. * 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, ongoing drug induced liver disease, nonalcoholic steatohepatitis (but not steatosis), hemochromatosis, or alpha-1-antitrypsin deficiency). * Active substance abuse, such as alcohol, inhaled or injection drugs within the previous year as determined by self-report or previous medical records. * Evidence of hepatocellular carcinoma. This will be determined on the basis of imaging with ultrasound/ CT scan or MRI performed a maximum of 6 months prior to enrollment. Elevated AFP levels will be evaluated clinically, and further imaging may be performed if felt necessary. * Evidence of concurrent hepatitis C infection with positive serum HCV RNA. * Any experimental therapy, previous use of lonafarnib or pegylated interferon therapy within 6 months prior to enrollment. * Active, serious autoimmune disease such as systemic lupus erythematosus, ulcerative colitis, Crohn s disease or rheumatoid arthritis, that is in the opinion of the investigators might be exacerbated by therapy with lambda interferon. This will be evaluated at baseline and during follow-up laboratory testing (including blood and urine studies) in addition to described symptoms at each outpatient visit. * Diagnosis of malignancy in the five years prior to the enrollment with exception granted to superficial dermatologic malignancies. * Evidence of HIV co-infection; HIV 1/2 antibody positivity on serum testing. * Concurrent usage of statins as these drugs inhibits mevalonate synthesis, which reduces protein prenylation. * Concurrent usage of moderate and strong CYP3A inhibitors and inducers. * 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. * Clinically significant baseline EKG abnormalities such as QTc interval \>450 ms and/or prolonged PR interval. * Uncontrolled elevated triglycerides (\>500 mg/dL). Patients on lipid lowering therapy other than statins will be eligible for this study. * History of pancreatitis from causes other than gallstone pancreatitis. Subjects with a baseline amylase and/or lipase level \>3 ULN will be excluded from the study. * Any other condition, which in the opinion of the investigators would impede the patient s participation or compliance in the study. * Inability to provide written informed consent.