Table 1 Key elements regarding hepatitis D in the guidelines addressing hepatitis B

AASLD

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Anti-HDV screening is recommended in HIV positive persons, persons who inject drugs, men who have sex with men, those at risk for sexually transmitted diseases, migrants from areas of high HDV endemicity, patients with low HBV-DNA levels and elevated ALT levels.

PegIFNα for 12 months is the recommended therapy for those with elevated HDV-RNA levels and ALT elevation. If HBV-DNA levels are elevated, concurrent therapy with NA is indicated.

Assessment of HDV-RNA is warranted if ALT elevation occurs following treatment because of the high rates of relapse.

Reasonable to refer patients to specialized centers that offer access to experimental therapies.

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EASL

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Severe or fulminant hepatitis is more frequently reported in HBV-HDV co-infection compared to HBV mono-infection. Chronic infection after acute HBV-HDV hepatitis is less common, while chronic delta hepatitis develops in 70–90% of patients with HDV superinfection.

Confirmed by detectable HDV RNA, immuno-histochemical staining for HDV antigen, or IgM anti-HDV. However, diagnosis of active HDV infection may be difficult, as HDV RNA assays are not standardised and HDV antigen and IgM anti-HDV assays are not widely available.

PegIFNα for at least 48 weeks is the current treatment of choice in HDV-HBV co-infected patients with compensated liver disease. It can be continued irrespective of on-treatment response pattern if well tolerated. Patients with ongoing HBV DNA replication, NA therapy should be considered.

Long-term follow-up HDV RNA monitoring is recommended for all treated patients as long as HBsAg is present.

Persistent HDV replication leads to cirrhosis and HCC at annual rates of 4 and 2.8%, leading to high fatality rate and justifying the need for antiviral therapy.

APASL

The prevalence of HDV has not declined. In the United States of America, Australia and some European countries, the prevalence of HDV infection is increasing.

Chronic infection after acute HBVHDV hepatitis is less common, while chronic hepatitis D develops in 70–90% of patients with HDV superinfection.

Confirmed by detectable HDV RNA, immuno-histochemical staining for HDV antigen, or IgM anti-HDV. But diagnosis of active HDV infection may be difficult, as HDV RNA assays are not standardized and HDV antigen and IgM anti-HDV assays are not widely available.

Pegylated interferon is effective against HDV. Weekly injection of pegylated interferon is currently used for 12–18 months. Nucleotide analogues treatment might be considered in some patients who have active HBV replication with persistent or fluctuating serum HBV DNA levels above 2000 IU/ml.

Patients should be monitored for 6 months post treatment and beyond.

HDV can cause severe liver injury that may result in fulminant hepatic failure and rapid progression to cirrhosis and hepatic decompensation, as well as an increased risk of liver cancer.

WGO

Up to 5% of the world’s population is infected with HBV, and probably 5% of those chronically infected with HBV have HDV infection. Some endemic areas in the developing world may have much higher prevalence.

Coinfection evolves to chronicity in only 2% of cases, but is associated with a higher chance of fulminant acute infection, while superinfection leads to progressive disease and cirrhosis in more than 80% of cases.

Should be evaluated particularly if hepatitis is present in the face of little or no HBV viral replication, or if they come from an HDV-endemic region or have acquired HBV through injection drug use. Infection should be diagnosed by detection of HDV RNA in serum by polymerase chain reaction, or indirectly by detection of antibodies against hepatitis D antigen of the IgG and IgM classes.

Chronic hepatitis D should be treated with IFN (preferably pegyIFN) for at least 12 months, but the treatment results are suboptimal. Patients with active HBV replication despite HDV coinfection may benefit from treatment with NA in combination with PegIFN.

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Cirrhosis develops at a younger age than in patients with chronic HBV monoinfection.