Abstract
Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5–8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20–30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals.
Highlights
The need for the narrative review article we propose to readers stems from the extensive literature developed in recent years on different aspects of hepatitis D virus (HDV)
The most often observed adverse events were lonafarnib-dependent gastrointestinal events and weight loss [127]. These data led the authors of the LOWR HDV-1 study to start a new therapeutic attempt with the LOWR HDV-2 study; 48 patients with chronic HDV infection were enrolled and divided into three groups respectively receiving a high dose lonafarnib ≥ 75 mg BID + RTV 100 mg BID (15 patients treated for 12 weeks), or a low dose lonafarnib (25 or 50 mg BID) + RTV 100 mg BID
Old and new data indicate that a prolonged ongoing of HDV replication is a strong independent predictor of development of cirrhosis and HCC, highlighting the need for drugs able to eliminate viral synthesis
Summary
The need for the narrative review article we propose to readers stems from the extensive literature developed in recent years on different aspects of hepatitis D virus (HDV). New antiviral agents directed against different replicative phases of the HDV life cycle have recently been produced and are in the initial phase of clinical experimentation, with preliminary favorable results. They too are burdened by adverse reactions, but their use in combination with other antiviral drugs seems to tone down these side effects. The availability of new information on different aspects of HDV infection led us to produce this narrative review, which is aimed at doctors and researchers who carry out their activities, in part or in full, in the field of hepatic diseases
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