Copyright ©The Author(s) 2021.
World J Gastroenterol. Jul 14, 2021; 27(26): 4018-4044
Published online Jul 14, 2021. doi: 10.3748/wjg.v27.i26.4018
Table 1 Features of different types of hepatitis virus

GenomePositive single-stranded linear RNADouble stranded gapped DNAPositive single-stranded linear RNANegative single-stranded circular RNAPositive single-stranded linear RNA
Genome length (kb)
Genotype6 genotypes: I, II and III infect humans, and IV, V and VI infect non-human primates10 genotypes (A to J)8 (1 to 8)8 (1 to 8)8 (1 to 8)
TransmissionFecal-oralParenteral, sexual, and perinatalExposure to infected bloodExposure to infected blood and body fluidsFecal-oral; zoonotic; blood transfusion
TreatmentNone. In case of severe hepatitis, treatment of symptomsPegylated interferon-alpha and nucleoside/nucleotide analoguesDAAPegylated interferon-alphaRibavirin (in chronic HEV infection)
ProphylaxisYes (inactivated vaccine)Yes (recombinant vaccine)NoYes (HBV vaccine)No2
Clinical outcome of infectionSelf-limitedSelf-limited and chronicSelf-limited and chronicSelf-limited and chronicSelf-limited
Chronic infection rateNoDepends on the age of acquisition of the infection. Birth or in infancy 90%, 1 yr and 5 yr of age 30%-50%, adulthood 5%. Hemodialysis patients 40%. Immune deficient patients 20%80%More frequent in HBV/HDV superinfection than coinfectionAcute infection in most of the cases. Chronic infection in immunosuppressed populations
Table 2 Hepatitis A virus highlights

Hepatitis A virus
1The risk of HAV infection is associated with the lack of safe water and poor and sanitation
2Due to the vaccine introduction in childhood, young adults are becoming more susceptible to HAV infections
3In countries where waterborne transmission is rare, outbreaks occur among men who have sex with men, injecting drug users and contaminated food
4Since molecular detection is not routinely performed for diagnosis, surveillance programs, including viral amplification and sequencing, are needed to know the strains that circulate in a certain place
5One of the greatest challenges for HAV is to increase vaccination coverage globally, still implementing the single-dose schedule, to decrease the new infections, and, in the long term, to achieve its eradication
Table 3 Hepatitis B virus highlights

Hepatitis B virus
1Several host factors, such as male gender, alcohol intake, and obesity have been associated to worse disease progression. Current challenge implies finding genetic markers to predict the course of HBV infection. In this line, different SNPs associated with the outcome of HBV infection have been recently identified
2In the last years, new diagnostic assays have been developed in the framework of the diagnosis of HBV infection. The implementation of quantitative HBsAg, HBcAg, and HBV-RNA in routine clinical practice could probably improve the management of patients with CHB
3Current antiviral treatments have some shortcomings, such as poor SVR or prolonged schedules. Direct antiviral agents against different HBV targets, including HBV cccDNA, are under evaluation. Moreover, immunemodulatory therapies to overcome host immune impairment observed in chronic infections are being investigated
4Although a safe and cost-effective vaccine is available since the 1980s, an inadequate response is achieved in particular settings. New and more potent adjuvants, as well as formulations that include alternative viral antigens could improve the response rate vaccination
5The development of new antiviral therapies that enables achieving functional cure as well as accurate diagnostic methods and more effective vaccines will contribute with the purpose of the WHO to eliminate by 2030 hepatitis as a global health problem
Table 4 Hepatitis C virus highlights

Hepatitis C virus
1WHO global hepatitis elimination strategy aims to reduce 90% of new HCV incidence, 65% of mortality and treat at least 80% of patients
2DAA treatment leads to regression of clinical symptoms and liver disease complications even in those patients with other comorbidities, co-infections, or advanced liver disease
3The immune response plays a central role in viral elimination. The understanding of the relationship between achieving protection and activation of immune responses is mandatory for the development of an effective prophylactic vaccine
4Immune response restoration after DAA treatment is also under debate, certain immune features are reinvigorated, but many immune exhaustion signs may persist
5SVR after DAA rates higher than 97% are usually attained, but still, a minor group of patients (4%-5%) fails to eradicate HCV due to resistance-associated variants, some of them arising after treatment but others naturally occurring in treatment naïve individuals
6DAA efficacy impacts on transplantation from HCV-infected donors into infected or uninfected recipients; however, early outcome data are encouraging, experience is limited, and many issues remain under debate
7HCC risk after DAA treatment has been extensively discussed; however, recent seminal reports support the notion of a reduced rate for occurrence or recurrence of HCC after DAA SVR
9There are numerous HCV vaccine approaches including a few candidates who accomplished phase I trials, but a prophylactic HCV vaccine that can contribute to the eradication goal remains a pending issue
Table 5 Hepatitis D virus highlights

Hepatitis D virus
1The natural course and outcome of acute hepatitis D differ according to HBV and HDV co-infection or superinfection
2HDV and HBV genotypes in addition to host factors influence the course of chronic hepatitis
3The implications on liver disease of HVD, HBV, and innate immunity interplay remain to be understood
4Chronic setting leads to more severe hepatitis associated with higher rates of HCC and a faster progression to cirrhosis compared with HBV monoinfection. HDV pathologic changes are limited to the liver with histopathologic features that are not specific for it
5HDV remains difficult to treat with the current available therapies, and although, several promising new therapies have been described treatment is still the greatest challenge in HDV infection
Table 6 Hepatitis E virus highlights

Hepatitis E virus
1HEV is transmitted by the fecal-oral route (involving contaminated waters) and also as a zoonosis
2In the last years, many studies have focused on HEV detection in environmental and food matrices, and blood products as alternative sources of infection
3A new etiological agent of human hepatitis E, Orthohepevirus C, previously known to infect rats, has been recently described
4Although most cases of HEV infection produce acute hepatitis, chronic infections seem to be an increasing problem, particularly in Europe
5Complications and extrahepatic manifestations are also increasingly recognized
6Only one vaccine for HEV has been licensed in China, with little known data, which limits its use