Compensated liver disease

Also known as: Compensated Cirrhosis / Liver Cirrhosis / Cirrhosis / Cirrhosis (of liver) NOS / Cirrhosis of liver / Cirrhosis liver / Hepatic cirrhosis NOS / Hepatic cirrhosis

DrugDrug NameDrug Description
DB11586AsunaprevirAsunaprevir, also named as BMS-650032, is a potent hepatitis C virus (HCV) NS3 protease inhibitor. It has been shown to have a very high efficacy in dual-combination regimens with daclatasvir in patients chronically infected with HCV genotype 1b.[A32528] It was developed by Bristol-Myers Squibb Canada and approved by Health Canada on April 22, 2016. The commercialization of asunaprevir was canceled one year later on October 16, 2017.[L1113]
DB08873BoceprevirBoceprevir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Boceprevir. Boceprevir is an inhibitor of NS3/4A, a serine protease enzyme, encoded by HCV genotypes 1 and 4 [synthesis]. These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS4A, NS4B, NS5A and NS5B [FDA Label]. The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs [A19593]. Subtitutions at amino acid positions 155, 156, or 168 are known to confer resistance. The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself. Despite this disadvantage Boceprevir is still effective against HCV when paired with [DB00811], [DB00008], and [DB00022]. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) do not reccomend Boceprevir in combination with [DB00811], [DB00008], and [DB00022] as first line therapy for Hepatitis C [A19593]. Boceprevir, [DB00811], [DB00008], and [DB00022] are used with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Boceprevir is available as a fixed dose product (tradename Victrelis) used for the treatment of chronic Hepatitis C. Approved in May 2011 by the FDA, Victrelis is indicated for the treatment of HCV genotype 1 in combination with [DB00811], [DB00008], and [DB00022] [FDA Label]. Victrelis is no longer widely used as interferon-free therapies have been developed.
DB00105Interferon alfa-2bInterferon alpha 2b (human leukocyte clone hif-sn 206 protein moiety reduced). A type I interferon consisting of 165 amino acid residues with arginine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent.
DB00008Peginterferon alfa-2aPeginterferon alfa-2a is a form of recombinant interferon used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) resulting in less use of Peginterferon alfa-2a. Peginterferon alfa-2a is derived from the alfa-2a moeity of recombinant human interferon and acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body's innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Use of Peginterferon alfa-2a is associated with a wide range of severe adverse effects including the aggravation and development of endocrine and autoimmune disorders, retinopathies, cardiovascular and neuropsychiatric complications, and increased risk of hepatic decompensation in patients with cirrhosis. The use of Peginterferon alfa-2a has largely declined since newer interferon-free antiviral therapies have been developed. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) no longer recommend Peginterferon alfa-2a for the treatment of Hepatitis C [A19593]. Peginterferon alfa-2a was used alongside [DB00811] with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Peginterferon alfa-2a is available as a fixed dose injector (tradename Pegasys) used for the treatment of chronic Hepatitis C. Approved in 2002 by the FDA, Pegasys is indicated for the treatment of HCV with [DB00811] or other antiviral drugs [FDA Label]. When combined together, Peginterferon alfa-2a and [DB00811] have been shown to achieve a SVR between 36% for genotype 1 and 59% for genotypes 2-6 after 48 weeks of treatment.
DB00022Peginterferon alfa-2bPeginterferon alfa-2b is a form of recombinant interferon used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) resulting in less use of Peginterferon alfa-2b. Peginterferon alfa-2b is derived from the alfa-2b moeity of recombinant human interferon and acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body's innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Use of Peginterferon alfa-2b is associated with a wide range of severe adverse effects including the aggravation and development of endocrine and autoimmune disorders, retinopathies, cardiovascular and neuropsychiatric complications, and increased risk of hepatic decompensation in patients with cirrhosis. The use of Peginterferon alfa-2b has largely declined since newer interferon-free antiviral therapies have been developed. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) no longer recommend Peginterferon alfa-2b for the treatment of Hepatitis C [A19593]. Peginterferon alfa-2b was used alongside [DB00811] with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Peginterferon alfa-2b is available as a variable dose injectable product (tradename Pegintron) used for the treatment of chronic Hepatitis C. Approved in 2001 by the FDA, Pegintron is indicated for the treatment of HCV with [Ribavirin] or other antiviral drugs [FDA Label]. When combined together, Peginterferon alfa-2b and [Ribavirin] have been shown to achieve a SVR between 41% for genotype 1 and 75% for genotypes 2-6 after 48 weeks of treatment.
DB00811RibavirinProducing a broad-spectrum activity against several RNA and DNA viruses, Ribavirin is a synthetic guanosine nucleoside and antiviral agent that interferes with the synthesis of viral mRNA. It is primarily indicated for use in treating hepatitis C and viral hemorrhagic fevers. HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. It is reported that ribavirin might be only effective in early stages of viral hemorrhagic fevers including Lasser fever, Crimean-Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and Hantavirus infection. Ribavirin is a prodrug that is metabolized into nucleoside analogs that blocks viral RNA synthesis and viral mRNA capping. Before the development of newer drugs, ribavirin and [DB00008]/[DB00022] dual therapy was considered the first-generation and standard antiviral treatment [A19626]. The dual therapy was administered for 48 weeks in patients with genotype 1, 4, 5, and 6, and 24 weeks in patients with genotype 2 and 3 [A19626]. Newer drugs developed as Hepatitis C viral infection treatments can be used to reduce or eliminate the use of ribavirin, which are associated with serious adverse effects. They also improve therapeutic efficacy in patients with failed [DB00008]/[DB00022] and ribavirin-based therapy. The potential use of ribavirin as a treatment for acute myeloid leukemia is currently under investigation. According to 2017 American Association for the Study of Liver Diseases (AASLD) and 2015 consensus guidelines from the Canadian Association for the Study of the Liver (CASL), ribavirin is typically used as an adjunct therapy to various first-line and second-line combination therapies recommended for each genotypes. Ribavirin is added to decrease relapse rates by accelerating viral clearance early in the treatment course [A19645]. When used to treat Hepatitis C virus (HCV) infections, it is always used as a part of combination therapies as ribavirin monotherapy is not efficacious in the treatment of chronic hepatitis C infection [A19644]. Additionally, including ribavirin in the regimen can increase the risk of anemia. In HCV genotye 1/2/3/4/5/6 patients, ribavirin can be used in combination therapy involving [DB09102] and [DB08934], Eplusa ([DB08934], [DB11613]), Harvoni ([DB08934], [DB09027]), [DB06290] and [DB08934], Viekira Pak ([DB09296], [DB09297], [DB00503], [DB09183]), Technivie ([DB00503], [DB09296], [DB09297]) and Zepatier ([DB11574], [DB11575]). Addition of weight-based ribavirin to Technivie therapy increased sustained virologic response after 12 weeks of daily therapy (SVR12) from 90% to 97% in patients with HCV genotype 1a and 90.9% to 100% in HCV genotype 4 patients [L852]. Zepatier therapy along with ribavirin improved SVR in HCV genotype 5 patients. Combination therapy of ribavirin and [DB00008] results in the SVR of 44% in patients with genotype 1 infection and 70% in patients with genotype 2-6. The inclusion of ribavirin in the combination therapies depend on individual patient's profile, for example if HCV genotype 3 patient has a Y93H genetic variant and compensated cirrhosis.
DB09299Tenofovir alafenamideTenofovir alafenamide is a novel [tenofovir] prodrug developed in order to improve renal safety when compared to the counterpart [tenofovir disoproxil].[A178060] Both of these prodrugs were first created to cover the polar phosphonic acid group on tenofovir by using a novel oxycarbonyloxymethyl linkers to improve the oral bioavailability and intestinal diffusion.[T239] Tenofovir alafenamide is an alanine ester form characterized for presenting low systemic levels but high intracellular concentration.[A178219] It has been reported to produce a large antiviral efficacy at doses ten times lower than tenofovir disoproxil.[A178327] The first approved product including tenofovir alafenamide was developed by Gilead Sciences Inc and FDA approved on 2015.[L6271]
DrugDrug NameTargetType
DB11586AsunaprevirHepatitis C virus NS3 protease/helicasetarget
DB11586AsunaprevirMultidrug resistance protein 1carrier
DB11586AsunaprevirSolute carrier organic anion transporter family member 1B1carrier
DB11586AsunaprevirSolute carrier organic anion transporter family member 2B1carrier
DB11586AsunaprevirCYP3Aenzyme
DB11586AsunaprevirCytochrome P450 3A4enzyme
DB11586AsunaprevirCytochrome P450 3A5enzyme
DB11586AsunaprevirCytochrome P450 2A6enzyme
DB11586AsunaprevirCytochrome P450 2B6enzyme
DB11586AsunaprevirCytochrome P450 2C9enzyme
DB11586AsunaprevirCytochrome P450 2C19enzyme
DB11586AsunaprevirCytochrome P450 2D6enzyme
DB11586AsunaprevirSolute carrier organic anion transporter family member 1B1transporter
DB11586AsunaprevirSolute carrier organic anion transporter family member 1B3transporter
DB11586AsunaprevirSolute carrier organic anion transporter family member 2B1transporter
DB08873BoceprevirCytochrome P450 3A4enzyme
DB08873BoceprevirCytochrome P450 3A5enzyme
DB08873BoceprevirMultidrug resistance protein 1transporter
DB08873BoceprevirNS3/4A proteintarget
DB00105Interferon alfa-2bInterferon alpha/beta receptor 2target
DB00105Interferon alfa-2bInterferon alpha/beta receptor 1target
DB00105Interferon alfa-2bCytochrome P450 1A2enzyme
DB00008Peginterferon alfa-2aInterferon alpha/beta receptor 2target
DB00008Peginterferon alfa-2aInterferon alpha/beta receptor 1target
DB00008Peginterferon alfa-2aCytochrome P450 1A2enzyme
DB00022Peginterferon alfa-2bInterferon alpha/beta receptor 1target
DB00022Peginterferon alfa-2bInterferon alpha/beta receptor 2target
DB00022Peginterferon alfa-2bCytochrome P450 1A2enzyme
DB00022Peginterferon alfa-2bCytochrome P450 2D6enzyme
DB00022Peginterferon alfa-2bCytochrome P450 2C9enzyme
DB00811RibavirinRNA-directed RNA polymerase Ltarget
DB00811RibavirinEctonucleotide pyrophosphatase/phosphodiesterase family member 1target
DB00811RibavirinRNA-directed RNA polymerase catalytic subunittarget
DB00811RibavirinCytosolic purine 5'-nucleotidasetarget
DB00811RibavirinInosine-5'-monophosphate dehydrogenase 1target
DB00811RibavirinGenome polyproteintarget
DB00811RibavirinInosine-5'-monophosphate dehydrogenase 2target
DB00811RibavirinAdenosine kinaseenzyme
DB00811RibavirinEquilibrative nucleoside transporter 1transporter
DB00811RibavirinSolute carrier family 28 member 3transporter
DB09299Tenofovir alafenamideReverse transcriptase/RNaseHtarget
DB09299Tenofovir alafenamideMultidrug resistance protein 1transporter
DB09299Tenofovir alafenamideMultidrug resistance-associated protein 4transporter
DB09299Tenofovir alafenamideSolute carrier family 22 member 6transporter
DB09299Tenofovir alafenamideSolute carrier family 22 member 8transporter
DB09299Tenofovir alafenamideLysosomal protective proteinenzyme
DB09299Tenofovir alafenamideLiver carboxylesterase 1enzyme
DB09299Tenofovir alafenamideATP-binding cassette sub-family G member 2transporter
DB09299Tenofovir alafenamideSolute carrier organic anion transporter family member 1B1transporter
DB09299Tenofovir alafenamideSolute carrier organic anion transporter family member 1B3transporter
DB09299Tenofovir alafenamideReverse transcriptasetarget
DB09299Tenofovir alafenamideDNA polymerasetarget
DB09299Tenofovir alafenamideSerum albumincarrier
DB09299Tenofovir alafenamideCytochrome P450 3A4enzyme
DB09299Tenofovir alafenamideAdenylate kinase isoenzyme 1enzyme
DB09299Tenofovir alafenamideAdenylate kinase 2, mitochondrialenzyme
DB09299Tenofovir alafenamideNucleoside diphosphate kinase Aenzyme
DB09299Tenofovir alafenamideNucleoside diphosphate kinase Benzyme
DrugDrug NamePhaseStatusCount
DB09183Dasabuvir2Completed1
DB13879Glecaprevir2Completed1
DB09296Ombitasvir2Completed1
DB09297Paritaprevir2Completed1
DB13878Pibrentasvir2Completed1
DB00811Ribavirin2Completed1
DB00503Ritonavir2Completed1
DB09183Dasabuvir3Completed2
DB11574Elbasvir3Not Yet Recruiting1
DB13879Glecaprevir3Completed1
DB11575Grazoprevir3Not Yet Recruiting1
DB05990Obeticholic acid3Recruiting1
DB09296Ombitasvir3Completed2
DB09297Paritaprevir3Completed2
DB13878Pibrentasvir3Completed1
DB00811Ribavirin3Completed2
DB00503Ritonavir3Completed2
DB00811Ribavirin4Recruiting1