Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute HEV infection

1st line – supportive care

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ACUTE
|
acute HEV infection
|
non-pregnant
1st line – 

supportive care

Acute HEV infection typically does not require treatment other than supportive care as it resolves spontaneously in almost all patients.[1][2]​​

Advise the patient to rest, consume adequate nutrition and fluids, avoid drinking alcohol, and check with their physician before taking drugs that may potentially cause hepatic damage (e.g., paracetamol).[1]

Counsel the patient on hand hygiene to prevent transmission of HEV, particularly with respect to food handling practices.

Some patients, such as those with chronic liver disease, people with weakened immune systems, and older people, can experience more severe infection. These patients may require closer observation to monitor for deterioration in liver function.[32]

Consider – immunosuppression therapy taper

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ACUTE
|
acute HEV infection
|
non-pregnant
Consider – 

immunosuppression therapy taper

Additional treatment recommended for SOME patients in selected patient group

Consider reduction of immunosuppression therapy (wherever possible) in patients with solid organ transplant who have acute HEV infection, to assist with viral clearance.​[25][54]​ Acute HEV infection in solid organ transplant recipients has been shown to resolve spontaneously in over 30% of cases.​[25][54]

Consider – ribavirin

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ACUTE
|
acute HEV infection
|
non-pregnant
Consider – 

ribavirin

Additional treatment recommended for SOME patients in selected patient group

Consider treatment with ribavirin for patients with severe acute HEV infection, patients who are at increased risk of progression to hepatic decompensation, and those with acute-on-chronic liver failure.[2]

Case reports of ribavirin in acute HEV infection (or acute HEV infection occurring in underlying liver disease) have suggested that liver enzymes may rapidly normalise, with HEV RNA levels becoming undetectable within days of initiation of treatment.[62]

Ribavirin is associated with adverse effects, particularly dose-dependent anaemia. Regular monitoring of FBCs is required in all patients, and dose reduction, with or without transfusion, may be required in patients who develop anaemia.[2][25]

Women of childbearing age, and men who may have sex with women of childbearing age, should be counselled regarding the use of contraception during treatment with ribavirin and after treatment has stopped.

Assess response to ribavirin with serum alanine aminotransferase (ALT) and HEV RNA in stool and serum. Stop ribavirin if HEV RNA in both stool and serum are negative as this indicates a sustained viral response. Continue ribavirin for a further 3-6 months if there is persistence of HEV RNA in either stool or serum following the initial 3 months of treatment.[2][41]

Primary options

ribavirin: 600-800 mg/day orally given in 1-2 divided doses

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Consider – liver transplantation

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ACUTE
|
acute HEV infection
|
non-pregnant
Consider – 

liver transplantation

Additional treatment recommended for SOME patients in selected patient group

Refer patients who develop signs that may be suggestive of acute liver failure to a transplant centre for monitoring and consideration of a liver transplant.[63]​ See Acute liver failure.

1st line – supportive care

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ACUTE
|
acute HEV infection
|
pregnant
1st line – 

supportive care

Acute HEV infection typically does not require treatment other than supportive care as it resolves spontaneously in almost all patients.[1][2]​ However, it is important to note that acute HEV infection in pregnancy in endemic areas can lead to acute liver failure in upwards of 20% of women.[10]

Perform frequent monitoring of signs and symptoms as well as biochemical parameters in all pregnant women with acute HEV infection, under the combined management of the obstetric and specialist hepatology teams.

Consider hospital admission for pregnant women with symptomatic acute HEV infection on a case-by-case basis.[1][15]​​ Based on clinical experience in practice, indications for admission include evidence of deteriorating liver function and concern for fetal viability. Also consider hospital admission for pregnant women with solid organ transplant who have acute HEV infection (seek expert advice).

If hospital admission is not indicated, advise the patient to rest, consume adequate nutrition and fluids, avoid drinking alcohol, and check with their physician before taking drugs that may potentially cause hepatic damage (e.g., paracetamol).[1] Counsel the patient on hand hygiene to prevent transmission of HEV, particularly with respect to food handling practices.

Consider – liver transplantation

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ACUTE
|
acute HEV infection
|
pregnant
Consider – 

liver transplantation

Additional treatment recommended for SOME patients in selected patient group

Acute HEV infection in pregnancy in endemic areas can lead to acute liver failure in upwards of 20% of women.[10]

Treatment in a high-dependency treatment setting may be required for symptomatic pregnant patients, and transfer to a transplant centre will be required if signs of liver failure are present.[2]

ONGOING

chronic HEV infection: non-pregnant

1st line – immunosuppression therapy taper

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ONGOING
|
chronic HEV infection: non-pregnant
|
with solid organ transplant
1st line – 

immunosuppression therapy taper

Where possible, decrease immunosuppression therapy at diagnosis of chronic HEV infection in recipients of solid organ transplants.[2][25][41]

A systematic review of data from 21 studies of immunocompromised patients with HEV infection showed that reduction of immunosuppressive drugs induced clearance of HEV in 32% of patients.[64]

A retrospective analysis of data from 17 centres from the US and Europe, including 85 recipients of solid organ transplants who were chronically infected with HEV, noted that 32.1% achieved viral clearance when the dose of immunosuppressive drugs was reduced.[54]

Plus – supportive care

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ONGOING
|
chronic HEV infection: non-pregnant
|
with solid organ transplant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Advise all patients with chronic HEV to avoid drinking alcohol and check with their physician before taking drugs that may potentially cause hepatic damage (e.g., paracetamol).[1]

Counsel the patient on hand hygiene to prevent transmission of HEV, particularly with respect to food handling practices.

2nd line – ribavirin

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ONGOING
|
chronic HEV infection: non-pregnant
|
with solid organ transplant
2nd line – 

ribavirin

Give ribavirin for 3 months to transplant recipients with chronic HEV infection in whom reduction of immunosuppression is not possible or is unsuccessful.[2][41]​​

There have been no placebo-based trials for the use of ribavirin in chronic HEV infection; treatment recommendations are based on the results of case reports and case series.[57][65][66]​​[67]

One meta-analysis of the effect of ribavirin in 395 immunosuppressed patients with chronic HEV infection found that 301 patients (76%) achieved a sustained viral response following 3 months of therapy.[64]

A retrospective, multi-centre case series assessing the effects of ribavirin in 59 solid organ transplant recipients treated for a median of 3 months demonstrated a 78% sustained viral response rate in these patients.[67] Another study of 6 recipients of kidney transplants with chronic HEV infection found that HEV RNA was undetectable in the serum of all patients after 3 months of ribavirin.[57]

Ribavirin is associated with adverse effects, particularly dose-dependent anaemia. Regular monitoring of FBCs is required in all patients, and dose reduction, with or without transfusion, may be required in patients who develop anaemia.[2][25]

Women of childbearing age, and men who may have sex with women of childbearing age, should be counselled regarding the use of contraception during treatment with ribavirin and after treatment has stopped.

Assess response to ribavirin with serum alanine aminotransferase (ALT) and HEV RNA in stool and serum. Stop ribavirin if HEV RNA in both stool and serum are negative as this indicates a sustained viral response. Continue ribavirin for a further 3-6 months if there is persistence of HEV RNA in either stool or serum following the initial 3 months of treatment.[2][41]

Primary options

ribavirin: 600-800 mg/day orally given in 1-2 divided doses

More

Plus – supportive care

Back
ONGOING
|
chronic HEV infection: non-pregnant
|
with solid organ transplant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Advise all patients with chronic HEV to avoid drinking alcohol and check with their physician before taking drugs that may potentially cause hepatic damage (e.g., paracetamol).[1]

Counsel the patient on hand hygiene to prevent transmission of HEV, particularly with respect to food handling practices.

3rd line – peginterferon alfa

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ONGOING
|
chronic HEV infection: non-pregnant
|
with solid organ transplant
3rd line – 

peginterferon alfa

Consider switching to peginterferon alfa 2a in liver transplant recipients, on a case-by-case basis, if HEV RNA is still positive after 6 months of ribavirin.[2]​​[25][41]​​​​ Peginterferon alfa 2a may also be considered as an alternative treatment option to ribavirin in these patients, on a case-by-case basis, if ribavirin is not tolerated.[41]

Peginterferon alfa may be considered based on efficacy in small case series, but is associated with the risk of rejection in solid organ transplant recipients except liver transplant.[2]​ Treatment of these patients with peginterferon alfa should only be performed at, or in consultation with, a transplant centre.

A systematic review of studies that identified 13 immunosuppressed patients with chronic HEV infection who were treated with peginterferon alfa showed that a rapid virological response was noted in four patients (31%), and 11 patients (84%) achieved sustained viral response.[64] However, acute transplantation rejection occurred in two patients during treatment.[64]

Peginterferon alfa may cause or aggravate fatal or life-threatening infectious, neuropsychiatric, autoimmune, and ischaemic disorders. Monitor patients closely.

Primary options

peginterferon alfa 2a: 180 micrograms subcutaneously once weekly

Plus – supportive care

Back
ONGOING
|
chronic HEV infection: non-pregnant
|
with solid organ transplant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Advise all patients with chronic HEV to avoid drinking alcohol and check with their physician before taking drugs that may potentially cause hepatic damage (e.g., paracetamol).[1]

Counsel the patient on hand hygiene to prevent transmission of HEV, particularly with respect to food handling practices.

1st line – ribavirin and/or peginterferon alfa

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ONGOING
|
chronic HEV infection: non-pregnant
|
without solid organ transplant
1st line – 

ribavirin and/or peginterferon alfa

In immunosuppressed patients who have not had a solid organ transplant, such as those with HIV or haematological disorders, a handful of case reports/small series have shown some efficacy with treatment with ribavirin, peginterferon alfa, or a combination of the two drugs.[68][69][70]

Ribavirin is associated with adverse effects, particularly dose-dependent anaemia. Regular monitoring of FBCs is required in all patients, and dose reduction, with or without transfusion, may be required in patients who develop anaemia.[2][25] Women of childbearing age, and men who may have sex with women of childbearing age, should be counselled regarding the use of contraception during treatment with ribavirin and after treatment has stopped.

Assess response to ribavirin with serum alanine aminotransferase (ALT) and HEV RNA in stool and serum. Stop ribavirin if HEV RNA in both stool and serum are negative as this indicates a sustained viral response. Continue ribavirin for a further 3-6 months if there is persistence of HEV RNA in either stool or serum following the initial 3 months of treatment.[2][41]

Peginterferon alfa may cause or aggravate fatal or life-threatening infectious, neuropsychiatric, autoimmune, and ischaemic disorders. Monitor patients closely.

Primary options

ribavirin: 600-800 mg/day orally given in 1-2 divided doses

More

and/or

peginterferon alfa 2a: 180 micrograms subcutaneously once weekly

Plus – supportive care

Back
ONGOING
|
chronic HEV infection: non-pregnant
|
without solid organ transplant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Advise all patients with chronic HEV to avoid drinking alcohol and check with their physician before taking drugs that may potentially cause hepatic damage (e.g., paracetamol).[1]

Counsel the patient on hand hygiene to prevent transmission of HEV, particularly with respect to food handling practices.

chronic HEV infection: pregnant

1st line – supportive care

Back
ONGOING
|
chronic HEV infection: pregnant
1st line – 

supportive care

Monitor pregnant women with chronic HEV infection, under the combined management of the obstetric and specialist hepatology teams. Consider hospital admission on a case-by-case basis. Based on clinical experience in practice, indications for admission include evidence of deteriorating liver function and concern for fetal viability.

Provide pregnant women with supportive care, if needed. Advise the patient to avoid drinking alcohol, consume adequate nutrition and fluids, and check with their physician before taking drugs that may potentially cause hepatic damage (e.g., paracetamol).[1]

Counsel the patient on hand hygiene to prevent transmission of HEV, particularly with respect to food handling practices. Note that ribavirin and peginterferon alfa are contraindicated in pregnancy due to their potential teratogenic effects.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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