Hepatitis D and E infection

Hepatitis Delta Virus (HDV)

HDV antibodies should be screened for in all HBsAg positive persons
In persons with positive HDV antibodies, HDV-RNA should be measured in order to assess activity of the disease
In persons with chronic HDV co-infection and significant liver fibrosis (≥ F2), long-term (at least 12 months) treatment with PEG-IFN might be considered in association with TDF-based ART
Non-invasive fibrosis markers (transient elastography and serum markers) should be used with caution in HIV/HBV co-infected persons with chronic HDV infection as there are no well-established thresholds
Because of its anti-HBV activity, TDF/TAF should be added, as part of ART, to PEG-IFN in order to reduce HBV-DNA load
Bulevirtide (2mg/d; s.c.) in combination with TDF/TAF is recommended in HDV-RNA positive persons with compensated liver disease and should be used where available. The optimal duration of treatment remains unclear. Treatment should be performed in centers with sufficient experience
People with HIV and HDV infection should be referred to university centers for treatment and if possible enrolled in trials on new drugs active against HDV
Treatment efficacy should be monitored with HBV-DNA and HDV-RNA measurements, when available, and with follow-up of biochemical and liver fibrosis estimates
Persistent off-treatment HDV-RNA negativity and anti-HBs seroconversion are the ideal goals of antiviral treatment for HDV even if they can only be obtained in a minority of persons. Histological remission of liver disease is a less ambitious but more likely achievable goal
In persons with HDV and ESLD or HCC, liver transplantation from HBsAg negative donors should be strongly considered. Transplant with anti-HBV prophylaxis post-OLTX cures HBV and HDV infection

Hepatitis E Virus (HEV)

Screening for HEV infection is warranted in persons with symptoms consistent with acute hepatitis, unexplained flares of aminotransferases (even if suspected drug induced liver injury), unexplained elevated liver function tests, neuralgic amyotrophy, Guillain-Barrè, encephalitis or proteinuria
Screening should include anti-HEV IgG and IgM and HEV-RNA in blood and if possible in stool
Treatment with RBV (600 mg daily) may be considered in cases of severe acute HEV, acute-on-chronic liver failure, extrahepatic HEV related disease or in persons with persisting HEV replication three months after first detection of HEV-RNA. RBV should be given for a duration of 12 weeks followed by HEV-RNA measurements in serum and stool. If HEV-RNA is undetectable in both, RBV can be stopped. In persons in whom HEV-RNA is still detectable in serum and/or stool, RBV may be continued for an additional three months. In the setting of chronic HEV infection in immunosuppressed persons, reduction in immunosuppression should be considered