The majority of persons currently treated for chronic hepatitis B require long‐term or lifelong therapy. New inhibitors of hepatitis B virus entry, replication, assembly, or secretion and immune ...modulatory therapies are in development. The introduction of these novel compounds for chronic hepatitis B necessitates a standardized appraisal of the efficacy and safety of these treatments and definitions of new or additional endpoints to inform clinical trials. To move the field forward and to expedite the pathway from discovery to regulatory approval, a workshop with key stakeholders was held in September 2016 to develop a consensus on treatment endpoints to guide the design of clinical trials aimed at hepatitis B cure. The consensus reached was that a complete sterilizing cure, i.e., viral eradication from the host, is unlikely to be feasible. Instead, a functional cure characterized by sustained loss of hepatitis B surface antigen with or without hepatitis B surface antibody seroconversion, which is associated with improved clinical outcomes, in a higher proportion of patients than is currently achieved with existing treatments is a feasible goal. Development of standardized assays for novel biomarkers toward better defining hepatitis B virus cure should occur in parallel with development of novel antiviral and immune modulatory therapies such that approval of new treatments can be linked to the approval of new diagnostic assays used to measure efficacy or to predict response. Combination of antiviral and immune modulatory therapies will likely be needed to achieve functional hepatitis B virus cure. Limited proof‐of‐concept monotherapy studies to evaluate safety and antiviral activity should be conducted prior to proceeding to combination therapies. The safety of any new curative therapies will be paramount given the excellent safety of currently approved nucleos(t)ide analogues. (Hepatology 2017).
The majority of persons currently treated for chronic hepatitis B require long-term or lifelong therapy. New inhibitors of hepatitis B virus entry, replication, assembly, or secretion and immune ...modulatory therapies are in development. The introduction of these novel compounds for chronic hepatitis B necessitates a standardised appraisal of the efficacy and safety of these treatments and definitions of new or additional endpoints to inform clinical trials. To move the field forward and to expedite the pathway from discovery to regulatory approval, a workshop with key stakeholders was held in September 2016 to develop a consensus on treatment endpoints to guide the design of clinical trials aimed at hepatitis B cure. The consensus reached was that a complete sterilising cure, i.e., viral eradication from the host, is unlikely to be feasible. Instead, a functional cure characterised by sustained loss of hepatitis B surface antigen with or without hepatitis B surface antibody seroconversion, which is associated with improved clinical outcomes, in a higher proportion of patients than is currently achieved with existing treatments is a feasible goal. Development of standardised assays for novel biomarkers toward better defining hepatitis B virus cure should occur in parallel with development of novel antiviral and immune modulatory therapies such that approval of new treatments can be linked to the approval of new diagnostic assays used to measure efficacy or to predict response. Combination of antiviral and immune modulatory therapies will likely be needed to achieve functional hepatitis B virus cure. Limited proof-of-concept monotherapy studies to evaluate safety and antiviral activity should be conducted prior to proceeding to combination therapies. The safety of any new curative therapies will be paramount given the excellent safety of currently approved nucleos(t)ide analogues.
Only 20 years after the discovery of the hepatitis C virus, a cure is now likely for most people with chronic infection. This review considers current therapy and the present landscape of drug ...development for hepatitis C.
Only 20 years after the discovery of the hepatitis C virus (HCV), a cure is now likely for most people affected by this chronic infection, which carries a substantial disease burden, not only in the United States but also worldwide.
1
The recent approval of two direct-acting antiviral agents that specifically inhibit viral replication has dramatically increased the viral clearance rate, from less than 10% with the initial regimen of interferon monotherapy to more than 70% with current therapy. Moreover, many other drugs targeting viral or host factors are in development, and some will almost certainly be approved in the coming . . .
Hepatitis D virus (HDV) is a small satellite virus that is present almost exclusively in persons with chronic hepatitis B virus (HBV) infection because of its dependence on HBV surface antigen ...(HBsAg) for transmission and infectivity. Among HBsAg-positive persons, approximately 5% are infected with HDV, which corresponds to approximately 12 million persons (95% confidence interval, 8.7 million to 18.7 million) worldwide.
1
The estimated prevalence of HDV infection in the United States is low (0.11% of persons).
2
Accordingly, chronic HDV infection qualifies for the Food and Drug Administration Orphan Drug Designation Program, a status that is typically granted for diseases that . . .
Natural History of Hepatitis C Lingala, Shilpa; Ghany, Marc G
Gastroenterology clinics of North America,
12/2015, Volume:
44, Issue:
4
Journal Article
Peer reviewed
Hepatitis C infection is a common cause of cirrhosis and indication for liver transplantation in the United States. The incidence of chronic hepatitis C has been declining, but rates of cirrhosis and ...hepatocellular carcinoma are projected to increase. The outcome of chronic hepatitis C is variable. It is estimated that 20% to 25% will develop cirrhosis over a 25-year to 30-year period. The rate of disease progression is influenced by many host, viral, and environmental factors. Few can be modified.
Chronic hepatitis B is prevalent worldwide and is a major contributor to death from cirrhosis and hepatocellular carcinoma. Thus, the goals of therapy are to prevent the development of cirrhosis, ...hepatocellular carcinoma and liver-related death. Safe and effective therapy is available but complete cure is not yet possible. The decision to treat is complex and must be individualized. Each of the three major liver societies, the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL) and the Asian Pacific Association for the Study of the Liver (APASL) have developed treatment guidelines to provide healthcare professionals guidance on management of chronic HBV infection. This review will cover the specific, evidence-based or expert opinion guideline recommendations on who should be treated, what to treat with, how to monitor, when to stop therapy and management of treatment failure.
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a novel coronavirus that emerged in late 2019, is posing an unprecedented challenge to global health. Coronavirus ...disease 2019 (COVID‐19), the clinical disease caused by SARS‐CoV‐2, has a variable presentation ranging from asymptomatic infection to life‐threatening acute respiratory distress syndrome and multiorgan failure. Liver involvement is common during COVID‐19 and exhibits a spectrum of clinical manifestations from asymptomatic elevations of liver function tests to hepatic decompensation. The presence of abnormal liver tests has been associated with a more severe presentation of COVID‐19 disease and overall mortality. Although SARS‐CoV‐2 RNA has been detected in the liver of patients with COVID‐19, it remains unclear whether SARS‐CoV‐2 productively infects and replicates in liver cells and has a direct liver‐pathogenic effect. The cause of liver injury in COVID‐19 can be attributed to multiple factors, including virus‐induced systemic inflammation, hypoxia, hepatic congestion, and drug‐induced liver disease. Among patients with cirrhosis, COVID‐19 has been associated with hepatic decompensation and liver‐related mortality. Additionally, COVID‐19’s impact on health care resources can adversely affect delivery of care and outcomes of patients with chronic liver disease. Understanding the underlying mechanisms of liver injury during COVID‐19 will be important in the management of patients with COVID‐19, especially those with advanced liver disease. This review summarizes our current knowledge of SARS‐CoV‐2 virus‐host interactions in the liver as well the clinical impact of liver disease in COVID‐19.
Background
The hepatitis B virus (HBV) affects an estimated 290 million individuals worldwide and is responsible for approximately 900 000 deaths annually, mostly from complications of cirrhosis and ...hepatocellular carcinoma. Although current treatment is effective at preventing complications of chronic hepatitis B, it is not curative, and often must be administered long term. There is a need for safe, effective, finite duration curative therapy.
Aim
Our aim was to provide a concise, up to date review of all currently available and emerging treatment options for chronic hepatitis B.
Methods
We conducted a search of PubMed, clinicaltrials.gov, major meeting s and pharmaceutical websites for publications and communications on current and emerging therapies for HBV.
Results
Currently approved treatment options for chronic hepatitis B include peginterferon alpha‐2a and nucleos(t)ide analogues. Both options do not offer a ‘complete cure’ (clearance of covalently closed circular DNA (cccDNA) and integrated HBV DNA) and rarely achieve a ‘functional cure’ (hepatitis B surface antigen (HBsAg) loss). An improved understanding of the viral lifecycle, immunopathogenesis and recent advances in drug delivery technologies have led to many novel therapeutic approaches that are currently being evaluated in clinical trials including targeting of viral entry, cccDNA, viral transcription, core protein, and release of HBsAg and HBV polymerase. Additionally, novel immunological approaches that include targeting the innate and adaptive immune system and therapeutic vaccination are being pursued.
Conclusion
The breadth and scope of novel therapies in development hold promise for regimen/s that will achieve functional cure.
Chronic hepatitis B virus (HBV) infection remains a major global health problem. Hepatitis B surface antigen (HBsAg) loss has been accepted as the definition of a functional HBV cure. Recent studies ...found that while covalently closed circular DNA (cccDNA) is the predominant source of HBsAg in hepatitis B e antigen-positive (HBeAg-positive) patients, integrated HBV DNA (iDNA) is the main source in HBeAg-negative patients. Consequently, achieving a functional HBV cure will require not only silencing of cccDNA but also iDNA. Assays that distinguish the source of HBsAg are needed to evaluate emerging therapies. In this issue of theJCI, Grudda et al. developed a PCR-based assay that differentiated the source of HBsAg and explored the contributing sources of HBsAg in patients on nucleos(t)ide analog antivirals. These findings provide a tool for understanding the contribution of iDNA in HBV infection and may guide therapies toward a functional HBV cure.
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