HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges

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.

Ropeginterferon alfa‐2b in patients with genotype 1 chronic hepatitis C: Pharmacokinetics, safety, and preliminary efficacy

“…The response rates range from 17 to 47%, however, with high relapse rates 28–32 . Longer treatment duration with marketed PEG‐IFN alpha or combination with nucleos( t )ide analogues such as adefovir, lamivudine, or entecavir did not increase the response rates 33,34 . Bulevirtide recently received conditional approval by European Medicines Agency for the treatment of CHD based on phase 2 data 35 .…”

“… 28 , 29 , 30 , 31 , 32 Longer treatment duration with marketed PEG‐IFN alpha or combination with nucleos( t )ide analogues such as adefovir, lamivudine, or entecavir did not increase the response rates. 33 , 34 Bulevirtide recently received conditional approval by European Medicines Agency for the treatment of CHD based on phase 2 data. 35 The preliminary result of ongoing trials by adding PEG‐IFN showed better treatment efficacy.…”

Epidemiology and aetiology of hepatocellular carcinoma in Sub-Saharan Africa

“…This estimate is considerably lower than those obtained in another study, which found 0.98% (95%CI: 0.61%-1.42%) in the general population and 14.57% (95%CI: 12.93%-16.27%) in HBsAg-positive individuals [138] . However, there were concerns about the populations selected, the markers and the HBsAg prevalence estimates used in the latter study that may have introduced biases [139] .…”

Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic

“…Eight genotypes of HDV have been identified at present, distributed differently in the world: Type 1 is present worldwide and prevalent in western Europe and North America, type 2 mainly in the Far East, Egypt and Iran, type 3 in the Amazon Basin, type 4 in Japan and Taiwan, types 5 to 8 in Africa but now spreading also in Western regions due to immigration flows[ 4 ]. In Western countries, HDV infection at present occurs mostly in elderly adults with chronic HBV infection or in young immigrants from endemic areas[ 5 ].…”

“…Chronic HDV infection is the most severe and rapidly progressive form of chronic hepatitis, leading to cirrhosis in 70% of patients within 5-10 years[ 7 ]. Furthermore, as compared with HBV mono-infection, HBV/HDV co-infection increases the risk up to three times of cirrhotic patients developing hepatocellular carcinoma[ 4 , 8 , 9 ].…”