Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice

Table 1 Similarities, differences and potential interactions across the major points of hepatitis E virus and hepatitis C virus infections

Categories	Similarity	Difference	Interaction
Epidemiology	High prevalence in developing countries[1]	HEV infects humans and animals[6,7]	Co-infections or superinfections[2,3]
Genetic variability	RNA viruses (quasispecies), genotype classification, recombination events[4,5]	Replication rate, HEV has non-enveloped or quasi-enveloped virions[12,26]	None
Pathogenesis	Disease progression in immunocompromised patients[32,54]	Microbiota alteration, hepatic severity[23,33,83,84]	HEV could influence hepatic or extrahepatic symptoms in patients with chronic HCV infection[2,3]
Treatment	Choice of therapy[35,50]	PEG-IFN-α and RBV are still the therapies of choice for HEV[35]	DAA therapy can be effective against both viruses[50,53]
Prevention	Public health measures[58]	Vaccine availability[60,62]	Improvement of screening policies[35,50]

DAA: Directly acting antivirals; PEG-IFN: Pegylated interferon; RBV: Ribavirin; HEV: Hepatitis E virus; HCV: Hepatitis C virus.

Table 2 Research perspectives for the next future

No.	Research perspectives for the next future
1	In vitro and in vivo studies to define pathogenic interactions during HEV/HCV coinfection. Cell lines model could explain interactions between viral proteins and cellular pathway responsible for liver fibrosis progression, liver steatosis and insulin resistance encountered in patients
2	Studies to understand relationships among immune phenomena (autoantibodies, cryoglobulins and autoimmune diseases) in patients infected by both viruses, and their correlated in terms of T- and B-cell responses and human leukocyte antigen type
3	Clinical trials to test safety and effectiveness of DAA in co-infected patients and new therapies. At present, data on DAA treatment is limited to in vitro studies or very few case reports
4	In vitro studies to evaluate genetic interactions between HEV and HCV during viral replication. Permissive cell lines, infected simultaneously by the two viruses, could show whether there is an interference or synergy between them during viral progeny production

DAA: Directly acting antivirals; HEV: Hepatitis E virus; HCV: Hepatitis C virus.