Non hepatotropic virus induced hepatitis - rising importance in a changing world

Table 1 Non hepatotropic viruses causing acute liver injury

Characteristics	Description
Herpes virus group
Type 1, 2	Herpes simplex virus
Type 3	Varicella zoster virus
Type 4	Epstein Barr virus
Type 5	Cytomegalovirus
Type 6	Human herpes virus
Emerging and re-emerging viruses
Hemorrhagic fever viruses
Flavivirus	Dengue virus subtypes 1-4, Yellow fever virus
Buniyaviridae	Crimean Congo haemorrhagic fever virus, Rift Valley fever virus, Lassa fever virus, Hantavirus
Filovirus	Ebola virus
Coronavirus	SARS-COV-2, SARS-COV-1, MERS COV
Orthomyxovirus	Influenza virus type A and B
Viruses predominantly affecting pediatric population but also immunocompromised adult host	Adenovirus type 41, Adeno-associated virus type 2, Parvovirus B19, Paramyxovirus (measles), Togavirus (rubella), Enterovirus (Coxsackie type A4, A9, B5 and echovirus), Norovirus

SARS-COV: Severe acute respiratory syndrome coronavirus, MERS COV: Middle East respiratory syndrome coronavirus.

Table 2 Epidemiologic features of viruses causing hemorrhagic fever

Virus name	Geographic areas, incubation period	Vector, host and transmission	Diagnosis, treatment, case fatality rate (in severe cases)	Prevention
Crimean Congo hemorrhagic fever	Africa, Asia and southern Europe (Balkan region)	Ixodid tick of Hyalomma spp	RT-PCR	Avoid tick bite; no vaccine available
		Cattle and other mammals	Ribavirin, methyl prednisolone
	1-5 days following a tick bite or 5-7 days following contact with infected blood	Humans acquire disease as accidental host by direct tick bite or contact with infected blood	5%-40%
Ebola fever	Mostly central and West Africa	Fruit bats reservoir	RT-PCR or ELISA for Ab	2 vaccines: (1) Ervebo (rVSV-ZEBOVGP), a live-attenuated vaccine, has very high efficacy after a single shot (up to 97.5%); and (2) One shot of Zabdeno (Ad26. ZEBOV-GP) followed by a shot of Mvabea (MVA-BN-Filo) 8 weeks later requires more time to induce protection (so not suitable for immediate effect in an outbreak) but protects over a longer period
	2-21 (6-10) days	Transmitted by direct contact or via bodily fluids of vector host (primates including humans)	Inmazeb (REGN-EB3), a mixture of 3 monoclonal Ab (atoltivimab/ maftivimab/odesivimab) given: 50 mg/kg in a single IV infusion, and Ebanga (Ansuvimab-zykl), a human monoclonal Ab 50 mg/kg administered within 1 hour
			50% (30% with treatment)
Lassa fever	West Africa	Rodents (multimammate rat of Mastomys spp)	RT-PCR. ELISA for IgM and IgG Ab	Avoid exposure to rhodents
	1-3 weeks	Inhalation of virus containing aerosolised rat excreta (urine, feces) or consuming contaminated foods or by direct contact with abraded skin. Human-to-human transmission may occur through direct contact with blood or bodily secretions from infected persons	Supportive and start ribavirin as early as possible: 15 mg/kg/day × 10 days	No vaccine available
			15%-20% (among 20% severe cases)
Hanta fever	Liver involvement only in HFRS (caused by Seoul type virus) found in Europe and Asia	Rodents	ELISA for Ab or immunofluorescence assay	Avoid contact with rhodents
	2-4 weeks	Virus containing aerosols in rodent excreta	Early ribavirin	No vaccine available
Rift Valley fever	Africa and the Arabian Peninsula	Arthropod borne, predominantly mosquitoes (Aedes and Culex species) from natural host i.e. livestock	RT-PCR, ELISA	Vaccinating livestock. Early detection in them and avoid contact
	2-6 days	Human transmission is by contact with animals	Ribavirin, favipiravir show in vitro effect only	No human vaccine available
			50% (among 5% severe cases)
Dengue fever	(Sub) tropical areas of America, Africa, Middle East, Asia and Pacific islands	Aedes aegypti, Aedes albopictus mosquitoes	RT-PCR, ELISA for IgM and IgG Ab, NS1 antigen	Mosquito repellent. Two WHO approved vaccines: (1) Dengvaxia (3 doses six months apart) for people aged 6-60 years but to be given only in laboratory-confirmed previous dengue virus infection; and (2) Qdenga (2 doses three months apart) in children aged 6-16 (upto 60 years for those with comorbidities) in high dengue transmission settings
	4-7 days	Mammals (mostly humans)	Supportive
			5% severe, acute liver failure in 0.5%
Yellow fever	(Sub) tropical Africa and South America	Sylvatic (forest) cycle: Africa (Aedes africanus), South America (Haemagogus and Sabethes species and urban cycle: Aedes aegypti (both Africa and South America). Primates	IgM Ab by ELISA	Mosquito repellent
	3-6 days		Supportive, ribavirin, sofosbuvir has been tried	Live attenuated vaccine given to 9 months or older individuals
			20%-60% (among 15% severe cases)	Other live vaccines are in phase III-IV trial

RT-PCR: Reverse transcriptase polymerase chain reaction; ELISA: Enzyme linked immunosorbent assay; HFRS: Hemorrhagic fever with renal syndrome; Ab: Antibodies.