Newer developments in viral hepatitis: Looking beyond hepatotropic viruses

Table 1 Example of non-hepatotropic viral infection causing hepatitis

Herpesvirus	HSV1, HSV2, HHV6, HHV7, HHV8, EBV, CMV, VZV
Adenovirus
Enterovirus	Coxsackie B virus, Echovirus
Paramyxovirus	Measles
Togavirus	Rubella
Parvovirus	Parvovirus B19
Coronavirus	COVID-19

COVID-19: Coronavirus disease 2019; HSV: Herpes simplex virus; HHV: Human herpes virus; EBV: Epstein-Barr virus; CMV: Cytomegalovirus.

Table 2 Strategies for cytomegalovirus prevention in liver transplant patients based on risk status

Risk status	Donor/Recipient CMV serological status	Prevention strategy
High risk	Donor positive/recipient negative	Prophylactic therapy for 3-6 mo
		Or
		Pre-emptive therapy requiring close monitoring
Intermediate risk	Donor positive/recipient positive	Prophylactic therapy for 3 mo
		Or
		Pre-emptive therapy requiring close monitoring
Intermediate risk	Donor negative/recipient positive	Prophylactic therapy for 3 mo
		Or
		Pre-emptive therapy requiring close monitoring
Low risk	Donor negative/recipient negative	No routing prophylaxis

CMV: Cytomegalovirus.

Table 3 Studies studying coronavirus disease 2019 infection and liver disease

Ref.	Patients	Type	Study highlight with regards to liver disease
Xie et al[148]	79	Retrospective study	Liver injury maybe related to systemic inflammation and liver function should be monitored in patients with severe pulmonary lesions on imaging
Zhang et al[149]	115	Retrospective study	Liver enzymes as well as INR significantly elevated in patients with severe COVID-19; Albumin low in severe cases
Huang et al[145]	41	Prospective case series	Two percent patients had chronic liver disease; 37% patients had elevated AST which was more pronounced in ICU patients
Fan et al[141]	148	Retrospective case series	In patients with abnormal liver function, more received treatment with lopinavir/ritonavir as compared to those with normal liver function
Wang et al[150]	138	Retrospective study	Of 2.9% patients had chronic liver disease, AST elevation > ALT and seen more in ICU patients
Xu et al[151]	62	Retrospective study	Of 12% patients had underlying liver disease; 16% patients had elevated AST
Shi et al[152]	81	Retrospective study	AST more elevated in patients with increasing pulmonary lesions on imaging; 9% patients had hepatitis or cirrhosis on imaging
Zhang et al[153]	82	Retrospective study; Jul 2020	Of 2.4% patients had underlying liver disease; 1.2% patients died due to liver disease; 30.6%, 61.1% and 30.6% had elevated levels of ALT, AST and Total bilirubin respectively
Guan et al[135]	1099	Retrospective study	There are 2.1% patients had hepatitis B; AST, ALT and Total bilirubin were elevated in 22.2%, 21.3% and 10.5% patients respectively
Ji et al[147]	202	Retrospective study	Liver injury frequent but mild in nature with mostly hepatocellular pattern; Patients with NAFLD and BMI had higher risk for persistent liver injury. Patients with NAFLD had higher risk for severe COVID-19 and longer viral shedding.
Mao et al[154]	6686	Systematic Review and Meta-analysis	Pooled prevalence of liver comorbidities was 3%. Pooled prevalence of liver injury was 19%; Patients with severe COVID-19 had higher risk for abnormal liver enzymes.
Singh et al[155]	2780	Multicenter research network study	Patients with cirrhosis and pre-existing liver disease are at increased risk for hospitalization and death
Bloom et al[143]	60	Prospective cohort study	Predominant AST elevation commonly seen in COVID-19 and correlates with disease severity
Wang et al[156]	105	Retrospective study	Elevated liver enzymes more likely in patients with severe COVID-19
Cai et al[157]	417	Cross sectional study	Of 76.3% patients had abnormal liver enzymes and 21.5% had liver injury during hospitalization; Patients who received lopinavir/ritonavir had higher odds of liver injury. Patients with abnormal liver tests had higher chance of severe COVID-19

INR: International normalized ratio; COVID-19: Coronavirus disease-2019; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ICU: Intensive Care Unit; NAFLD: Non-alcoholic fatty liver disease; BMI: Body mass index.

Table 4 Studies evaluation coronavirus disease 2019 infection post liver transplantation

Ref.	Patients	Type	Study highlight with regards to liver transplant
Coll et al[168]	110	Retrospective	Higher incidence of COVID (two-fold) in solid organ transplant patients. Eighty-five percent patients had adjustment in their immunosuppression
Becchetti et al[169]	57	Multicenter Prospective	Of 12% overall fatality rate and 17% in-hospital fatality rate. Patients with history of cancer had poorer outcomes
Colmonero et al[170]	111	Prospective	LT patients with increased risk of contracting COVID-19 but lower mortality when compared with matched general population. Dose reduction/withdrawal in mycophenolate helped prevent severe COVID-19 but complete discontinuation of immunosuppressants discouraged.
Webb et al[171]	151	Multicenter Prospective	Need for invasive mechanical ventilation and ICU admission more in LT group when compared with a control cohort – 20% vs 5 % and 28% vs 8% respectively. LT not independently associated with death, but presence of comorbidities and increased age were
Belli et al[172]	240	Multicenter retrospective	Of 84% patients required hospitalization, 25% of hospitalized patients died. Use of Tacrolimus associated with increased survival probability
Bhoori et al[159]	111	Retrospective	Three patients died of COVID-19 and all of them were male, > 65 years with multiple comorbidities and minimal immunosuppression
Rabiee et al[173]	112	Prospective	Hospital and ICU mortality rates lower rates in matched patients with chronic liver disease without LT
Mansoor et al[174]	126	Retrospective	Higher risk of hospitalization in LT patients. No difference in mortality and need for ICU in LT patients vs non- LT patients
Tejedor-Tejada et al[175]	16	Retrospective	Post COVID-19 syndrome present with mild symptoms but no loss of liver graft or graft dysfunction noted

LT: Liver transplant; ICU: Intensive care unit; COVID-19: Coronavirus disease-2019.