History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include presence of hepatitis B virus (HBV) infection, increased likelihood of sexual exposure, and injection drug use.[12]

uncommon

jaundice

May occur in some patients with acute HDV infection, following the initial incubation period of 3-7 weeks.[12][34][36]

ascites

Patients with chronic HDV infection and cirrhosis may have signs of chronic liver disease including ascites, palmar erythema, spider naevi (in the distribution of the superior vena cava), scleral icterus, splenomegaly, and loss of secondary sexual characteristics.

scleral icterus

Patients with chronic HDV infection and cirrhosis may have stigmata of chronic liver disease including scleral icterus, palmar erythema, spider naevi (in the distribution of the superior vena cava), ascites, splenomegaly, and loss of secondary sexual characteristics.

asterixis

Patients presenting with acute hepatic failure and hepatic encephalopathy may present with asterixis, which describes negative myoclonus detected by extending the arms, dorsiflexing the wrist, and spreading the fingers. This movement will elicit a flapping movement of the hands in patients with asterixis.

Other diagnostic factors

common

asymptomatic

Patients with both acute and chronic hepatitis D virus (HDV) infection (without cirrhosis or hepatocellular carcinoma) are often asymptomatic; infection should be suspected in patients at increased risk.

malaise

Acute HDV infection refers to the initial infection with HDV and occurs after an incubation period of 3-7 weeks. It may present as a self-limited flu-like illness. This may include symptoms of fever, malaise, fatigue, nausea, vomiting, and loss of appetite.[34][36]

fatigue

Acute HDV infection refers to the initial infection with HDV and occurs after an incubation period of 3-7 weeks. It may present as a self-limited flu-like illness. This may include symptoms of fever, malaise, fatigue, nausea, vomiting, and loss of appetite.[12][34][36]

uncommon

hepatomegaly

Patients with chronic HDV infection may have features of cirrhosis such as hepatomegaly, splenomegaly, and portal hypertension, along with signs of chronic liver disease.

fever

Acute HDV infection refers to the initial infection with HDV and occurs after an incubation period of 3-7 weeks. It may present as a self-limited flu-like illness. This may include symptoms of fever, malaise, fatigue, nausea, vomiting, and loss of appetite.[12][34][36]

right upper quadrant tenderness

May occur in some patients with acute HDV infection.

nausea/vomiting

Acute HDV infection refers to the initial infection with HDV and occurs after an incubation period of 3-7 weeks. It may present as a self-limited flu-like illness. This may include symptoms of fever, malaise, fatigue, nausea, vomiting, and loss of appetite.[12][34][36]

arthralgia/arthritis

Acute HDV infection occurs after an incubation period of 3-7 weeks. It may present as a self-limited flu-like illness. This may include symptoms of fever, malaise, fatigue, arthralgia/arthritis, nausea, vomiting, and loss of appetite.[12][34][36]

palmar erythema

Patients with chronic HDV infection and cirrhosis may have stigmata of chronic liver disease including palmar erythema, spider naevi (in the distribution of the superior vena cava), scleral icterus, ascites, splenomegaly, and loss of secondary sexual characteristics.

spider naevi

Spider naevi may occur in the distribution of the superior vena cava in patients with chronic HDV infection and cirrhosis.

splenomegaly

Patients with chronic HDV infection and cirrhosis may have stigmata of chronic liver disease including splenomegaly, palmar erythema, spider naevi (in the distribution of the superior vena cava), scleral icterus, ascites, and loss of secondary sexual characteristics.

loss of secondary sexual characteristics

Patients with chronic HDV infection and cirrhosis may have stigmata of chronic liver disease including loss of secondary sexual characteristics (such as loss of secondary sexual hair and testicular atrophy in men), palmar erythema, spider naevi (in the distribution of the superior vena cava), scleral icterus, ascites, and splenomegaly.

peripheral oedema

Patients with chronic HDV infection and decompensated cirrhosis may experience peripheral pitting oedema secondary to salt retention and reduced hepatic synthetic function leading to hypoalbuminaemia.

Risk factors

strong

HBV infection

The hepatitis D virus (HDV) requires hepatitis B virus (HBV) surface antigen to propagate. HDV infects susceptible hosts via simultaneous co-infection with HBV or via superinfection of an individual already infected with HBV. Around 5% of people infected with HBV (around 12 million people) have antibodies indicating infection with HDV. The majority have chronic HDV infection.[10]

increased likelihood of sexual exposure

Studies have shown sexual transmission of HDV in both heterosexual couples and in men who have sex with men. People deemed particularly at risk of HDV infection are those with increased likelihood of sexual exposure, including commercial sex workers, where reported prevalence may be up to 11%, with a pooled odds ratio of 18.7.[11][22][23] Increased likelihood of sexual exposure is also a risk factor for HBV infection, the presence of which is a requirement for HDV infection.[24][25]

injection drug use

Injection of drugs via shared needles can lead to percutaneous transmission of both HBV and HDV. Injection drug use has been reported in 18% of patients with a documented acute HBV infection.[24] One study of 652 patients, of which 91 had confirmed HDV, demonstrated that injection drug use was a significant predictor of HDV infection, with an adjusted odds ratio of 25.2 (95% CI 4.0 to 161.4, P=0.0007).[26] Injection drug use is also a risk factor for HBV infection, the presence of which is a requirement for HDV infection.[24][27]

weak

born or living in or travel to geographical regions where HDV is endemic

People born in regions of high incidence and prevalence (e.g., parts of western and mid-Africa, Mongolia, eastern Europe, and parts of the Mediterranean) are at increased risk of HDV infection.[11] People living in, or travelling to, highly endemic regions are also at greater risk.

history of incarceration

Since HDV infection occurs in the setting of HBV infection, patients with risk factors for HBV infection (e.g., injection drug use, increased likelihood of sexual exposure, being born in a highly endemic region) are also at risk for HDV infection.

Patients with a history of incarceration have a higher risk for HBV exposure due to associated risk factors (e.g., injection drug use, increased likelihood of sexual exposure, tattoos). In one systematic review in Europe, the highest prevalence of hepatitis B surface antigen among three high-risk groups (people who were incarcerated, men who have sex with men, and people who inject drugs) was found in those who were incarcerated (0.3% to 25.2%).[28]

family history of HBV/HDV infection, hepatocellular carcinoma, and/or chronic liver disease

People with a family history of HBV infection, HDV infection, hepatocellular carcinoma, and/or chronic liver disease have an increased risk of HDV infection.

perinatal exposure in an infant born to an HDV-infected mother

Vertical transmission of HDV is a rare but possible method of transmission. In one study of 36 children who were born to 22 mothers with HBV and HDV co-infection, only one child was found to be infected with HBV, and none had serological evidence of HDV.[29]

men who have sex with men

Many men who have sex with men are at a higher risk of contracting sexually transmitted infections and bloodborne pathogens, including HDV.[12]

household contact with HDV infection

Household contacts of people with HDV infection are at risk of becoming infected with HDV.[12] As with HBV infection, this may be due to continuous close, personal, or unnoticed contact of infective secretions with skin lesions or mucosal surfaces.[30]

healthcare workers

Healthcare and public safety workers who are at risk of occupational exposure to blood or blood contaminated fluids are at an increased risk of acquiring HDV infection.[12]

haemodialysis

The risk of acquiring HDV infection is increased in patients who receive haemodialysis.[12][31] One study that analysed the odds of anti-HDV detection in six selected populations relative to general populations or asymptomatic hepatitis B surface antigen (HBsAg)-positive people from the same geographical region found that anti-HDV prevalence was higher in haemodialysis recipients (pooled odds ratio 3.4).[11]

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