Pegylated Interferon Alpha-2B for the Management of Patients With Chronic Hepatitis Delta

Gheorghe, Liana; Iacob, Speranţa; Simionov, Iulia; Vadan, Roxana; Constantinescu, Ileana; Sporea, Ioan; Grigorescu, Mircea

doi:10.1016/s0016-5085(11)61863-5

Cited by 7 publications

(13 citation statements)

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“…46 Selected published studies are displayed in Table 1 including patients with chronic HDV infection who were treated with pegylated interferon-alfa-based treatment for at least 48 weeks and followed up for a minimum of 6 months. [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] The Hepatitis Delta International Intervention Trials (HIDIT-I and HIDIT-II) explored pegylated interferon-alfa-2a either in combination with adefovir or with tenofovir for 48 or 96 weeks in patients with HDV infections. 52,56 The trials were performed in Germany, Turkey, Greece and Romania.…”

Section: Tre Atment Of Hepatitis D Virus Infec Ti On With Interferon Smentioning

confidence: 99%

“…The combination of pegylated interferon‐alfa and ribavirin for 72 weeks did not lead to an improved virological or biochemical response rate with overall poor therapy tolerance 46 . Selected published studies are displayed in Table 1 including patients with chronic HDV infection who were treated with pegylated interferon‐alfa‐based treatment for at least 48 weeks and followed up for a minimum of 6 months 45–59 …”

Section: Treatment Of Hepatitis D Virus Infection With Interferonsmentioning

confidence: 99%

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Interferon‐based treatment of chronic hepatitis D

Sandmann

Wedemeyer

2022

Liver International

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Treatment of hepatitis D virus (HDV) infection has been based on the administration of interferon‐alfa for more than three decades. First studies to treat HDV‐infected patients with type 1 interferons were already performed in the 1980s. Several smaller trials and case series were reported thereafter. During the mid 2000s the use of pegylated interferons for hepatitis D was established. Since then, additional trials were performed in different countries exploring strategies to personalize treatment including extended treatment durations. The overall findings were that about one‐quarter to one‐third of patients benefit from interferon treatment with persistent suppression of HDV replication. However, only few patients achieve also functional cure of hepatitis B with HBsAg loss. Importantly, several studies indicate that successful interferon treatment is associated with improved clinical long‐term outcomes. Still, only a proportion of patients with hepatitis D can be treated with interferons. Even though alternative treatments are currently developed, it is likely that pegylated interferon‐alfa will still have an important role in the management of hepatitis D – either alone or in combination. Therefore, better biomarkers are needed to select patients with a high likelihood to benefit from interferon‐based treatments. In this review we are discussing basic principles of mode of action of interferon alpha against HDV, summarize previous data on interferon treatment of hepatitis D and give an outlook on potential combinations with novel drugs currently in development.

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Section: Tre Atment Of Hepatitis D Virus Infec Ti On With Interferon Smentioning

confidence: 99%

Section: Treatment Of Hepatitis D Virus Infection With Interferonsmentioning

confidence: 99%

Interferon‐based treatment of chronic hepatitis D

Sandmann

Wedemeyer

2022

Liver International

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“…However, SVR rates remained poor at 17%-43% despite the aforementioned "boosting effect" of insensitive HDV assays. [12][13][14][15]26] In the landmark Hep-Net International Intervention Trial (HIDIT) 1, a randomized controlled trial evaluating the safety and efficacy of 48 weeks of treatment with PEG-IFNα in combination with adefovir, PEG-IFNα alone, and adefovir alone, a combined primary endpoint of undetectable HDV RNA with ALT normalization was used. [15] Only four out of 60 patients (7%) in the PEG-IFNα groups met this primary combined endpoint despite approximately one quarter of patients (14 out of 60, 23%) achieving an undetectable HDV RNA and 30% of patients (18 out of 60) achieving ALT normalization at the end of treatment.…”

Section: The Evolution Of Clinical Trial Endpoints In Hdv the Interfe...mentioning

confidence: 99%

“…In compensated liver disease, the recommended treatment for HDV is pegylated interferon alpha (PEG‐IFNα) for at least 1 year 10,11. However, interferon therapy is limited by low rates of sustained virologic response (SVR) 6 months after treatment completion 12–15…”

Section: Introductionmentioning

confidence: 99%

Clinical trials in hepatitis D virus: Measuring success

2022

Hepatology

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Chronic hepatitis D infection results in the most severe form of chronic viral hepatitis but currently lacks effective treatment options. Therapy with pegylated interferon alpha is recommended for finite treatment duration by major liver societies. Still, it is plagued by low rates of sustained virologic response (SVR) and frequent relapses even if SVR is achieved. Recently, a wave of investigational therapies has come under evaluation, including bulevirtide, lonafarnib, pegylated interferon lambda, and REP‐2139 creating excitement with this viral infection. However, there has been significant variability in the endpoints used to evaluate these therapeutics. One of the recently introduced endpoints is characterized by a decline in HDV RNA by 2 logs, with or without achieving an undetectable serum hepatitis D virus (HDV) RNA, as a marker of virologic response. Furthermore, this measure has been combined with alanine aminotransferase normalization, also known as a biochemical response, to formulate the primary endpoint of several late‐stage studies. Per recent guidance by the US Food and Drug Administration, these should be surrogate endpoints that will ultimately portend long‐term clinical benefits. These clinical benefits may include reducing the risk of progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, liver transplantation, and mortality. However, the optimal way to measure success in HDV clinical trials remains unknown and will continue to evolve.

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“…PEG-IFN was the only available treatment that existed for HDV until recently. The evidence for this comes from a series of four randomized controlled trials and nine cohort studies [39][40][41][42][43][44][45][46][47][48][49][50][51] of HBV/HDV patients between 2006 and 2019. A recent meta-analysis by Abdrakhman et al 52 showed that PEG-IFN treatment had an estimated SVR risk difference of 0.29 [95% CI 0.24-0.34] for HDV RNA clearance over placebo, at 24 weeks off therapy.…”

Section: E Xis Ting Tre Atmentsmentioning

confidence: 99%

Future anti‐HDV treatment strategies, including those aimed at HBV functional cure

Tan

Lee

Huang

et al. 2022

Liver International

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HDV is a defective virus that uses the HBV surface antigen to enter hepatocytes. It is associated with an accelerated course of liver fibrosis progression and an increased risk of hepatocellular carcinoma. Negative HDV RNA 24 weeks after the end of therapy has been proposed as an endpoint but late relapses make this endpoint suboptimal, hence HBsAg loss appears to be more appropriate. Current HBV antiviral agents have poor activity against HDV hence the search for improved therapy. Drugs only active against HDV, such as lonafarnib, have shown efficacy in combination with nucleoside analogues and peginterferon, but do not lead to HBsAg loss. HBsAg loss sustained 24 weeks after the end of therapy with negative HBV DNA is termed functional cure.

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Pegylated Interferon Alpha-2B for the Management of Patients With Chronic Hepatitis Delta

Cited by 7 publications

References 0 publications

Interferon‐based treatment of chronic hepatitis D

Interferon‐based treatment of chronic hepatitis D

Clinical trials in hepatitis D virus: Measuring success

Future anti‐HDV treatment strategies, including those aimed at HBV functional cure

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