Hepatitis D natural history
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S. [2]; Jolanta Marszalek, M.D. [3]; João André Alves Silva, M.D. [4]
Overview
The clinical manifestations of HDV infection are similar to those of HBV infection, although infection with both may progress to more severe liver disease compared with HBV.
Natural History
HDV is a defective virus that requires individuals to be previously, or concomitantly, infected with HBV. After an initial incubation period of 3-7 weeks, the preicteric phase of acute HDV infection occurs with symptoms of fatigue, lethargy, anorexia and nausea, that last for 3 to 7 days. ALT and AST levels raise at this stage. Following the preicteric phase, the icteric phase is characterized by the manifestation of jaundice, acholic stools and dark urine. Serum bilirubin levels are also elevated at this stage. Fatigue and nausea continue to be present. In patients with acute, self-limiting infection, convalescence begins with the disappearance of clinical symptoms.[1]
Fulminant viral hepatitis is rare, however, its mortality rate may reach 80%, and is about 10 times more common in hepatitis D than in other types of viral hepatitis. It is characterized by:[1][2]
- Hepatic encephalopathy
- Sleep disturbances
- Confusion
- Concentration difficulties
- Abnormal behavior
- Somnolence
- Coma
About 60 to 70% of patients with chronic hepatitis D develop cirrhosis. Progression to cirrhosis usually takes 5 - 10 yrs, but it can appear 2 years after the onset of infection. Many of these patients die of hepatic failure.[1][3]
Coinfection
Coinfection with HBV and HDV results in both acute type B and type D hepatitis. The incubation depends on the HBV titer of the infective inoculum. One or two bouts of hepatitis may be seen depending on the relative titers of HBV and HDV.[4][5]
The host's response to HBV determines the fate of HDV. In more than 95% of adults, HDV is cleared, whereas the chronic form occurs in less than 5% of co-infected patients. Although disease presentation may differ greatly among patients, acute coinfection of HBV and HDV can result in a more severe disease state than acute mono-infection with HBV.[4][5]
Superinfection
HDV infection of a chronically infected HBV carrier frequently causes severe acute hepatitis with a short incubation period. The majority of cases lead to chronic hepatitis D.[4] This form of the disease often presents as acute hepatitis in a previously undiagnosed HBsAg carrier. Most times it is misdiagnosed as an acute form of HBV infection.[6]
Superinfection is associated with fulminant hepatitis and severe chronic active hepatitis, often progressing to cirrhosis. Less frequently, HDV replication stops and the natural history becomes that of the HBV infection. In cases where HDV replication stops, residual liver disease may still be more advanced. Superinfection can present as acute hepatitis in a previously undiagnosed carrier of HBsAg. It is sometimes misdiagnosed as acute HBV or as chronic HBV causing a worsening of the liver disease.[4]
Although it is associated with a higher rate of cirrhosis, a concomitant increase in the rate of HCC was not noted, possible due to the suppression of HBV replication, caused by HDV.[7]
Complications
Common complications of hepatitis D include:[5]
- Chronic active hepatitis
- Fulminant hepatitis
- Hepatic cirrhosis
- Hepatic failure
Hepatocellular Carcinoma
- Hepatocellular carcinoma (HCC) occurs in chronically infected HDV patients with advanced liver disease, with the same frequency as in those with hepatitis B.[1]
- HCC may be considered more a secondary effect of the associated cirrhosis than a direct carcinogenic effect of the virus, however further studies are required to evaluate this relationship.[1][8][9][10][11]
Prognosis
The mortality rate for HDV infections is between 2% and 20%. These values are ten times higher than those of hepatitis B.[1]
Patients with coinfection are more likely to have fulminant hepatitis than those with HBV infection alone. When acute infection with HDV occurs in a patient who has existing chronic HBV infection, especially in persons with progressive, symptomatic chronic disease, there is increased progression of hepatic cirrhosis and hepatic failure.[12]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf
- ↑ Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1451105630.
- ↑ Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1451105630.
- ↑ 4.0 4.1 4.2 4.3 World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf
- ↑ 5.0 5.1 5.2 Hughes SA, Wedemeyer H, Harrison PM (2011). "Hepatitis delta virus". Lancet. 378 (9785): 73–85. doi:10.1016/S0140-6736(10)61931-9. PMID 21511329.
- ↑ Farci P, Smedile A, Lavarini C, Piantino P, Crivelli O, Caporaso N; et al. (1983). "Delta hepatitis in inapparent carriers of hepatitis B surface antigen. A disease simulating acute hepatitis B progressive to chronicity". Gastroenterology. 85 (3): 669–73. PMID 6873613.
- ↑ Cross TJ, Rizzi P, Horner M, Jolly A, Hussain MJ, Smith HM; et al. (2008). "The increasing prevalence of hepatitis delta virus (HDV) infection in South London". J Med Virol. 80 (2): 277–82. doi:10.1002/jmv.21078. PMID 18098143.
- ↑ Heidrich B, Manns MP, Wedemeyer H (2013). "Treatment options for hepatitis delta virus infection". Curr Infect Dis Rep. 15 (1): 31–8. doi:10.1007/s11908-012-0307-z. PMID 23242761.
- ↑ Romeo R, Del Ninno E, Rumi M, Russo A, Sangiovanni A, de Franchis R; et al. (2009). "A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma". Gastroenterology. 136 (5): 1629–38. doi:10.1053/j.gastro.2009.01.052. PMID 19208358.
- ↑ Buti M, Homs M, Rodriguez-Frias F, Funalleras G, Jardí R, Sauleda S; et al. (2011). "Clinical outcome of acute and chronic hepatitis delta over time: a long-term follow-up study". J Viral Hepat. 18 (6): 434–42. doi:10.1111/j.1365-2893.2010.01324.x. PMID 20546496.
- ↑ Ji J, Sundquist K, Sundquist J (2012). "A population-based study of hepatitis D virus as potential risk factor for hepatocellular carcinoma". J Natl Cancer Inst. 104 (10): 790–2. doi:10.1093/jnci/djs168. PMID 22423008.
- ↑ Center for Substance Abuse Treatment. Screening for Infectious Diseases Among Substance Abusers. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 1993. (Treatment Improvement Protocol (TIP) Series, No. 6.) Chapter 15 - Viral Hepatitis D.