As with other types of viral hepatitis, (decompensated) cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality are potential complications of hepatitis D virus (HDV) infection.[66]Kamal H, Westman G, Falconer K, et al. Long-term study of hepatitis delta virus infection at secondary care centers: the impact of viremia on liver-related outcomes. Hepatology. 2020 Oct;72(4):1177-90.
https://www.doi.org/10.1002/hep.31214
http://www.ncbi.nlm.nih.gov/pubmed/32145073?tool=bestpractice.com
Patients with chronic HDV infection who have a higher risk of progression of liver disease include those with any of:[1]European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis delta virus. J Hepatol. 2023 Aug;79(2):433-60.
https://www.doi.org/10.1016/j.jhep.2023.05.001
http://www.ncbi.nlm.nih.gov/pubmed/37364791?tool=bestpractice.com
Elevated aminotransferases
Elevated gamma-glutamyl transpeptidase (GGT) levels
Advanced stage of liver disease
Persistent HDV viraemia
High serum hepatitis B virus (HBV) DNA levels
Viral co-infection
A history of other conditions associated with chronic liver disease (e.g., obesity, alcohol abuse, diabetes).
HDV infects susceptible hosts via simultaneous co-infection with HBV or via superinfection of an individual already infected with HBV. Very early studies suggest that both superinfection and co-infection with HDV increase the risk of fulminant hepatitis twofold compared with acute HBV infection alone.[67]Romeo R, Del Ninno E, Rumi M, et al. A 28-year study of the course of hepatitis delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009 May;136(5):1629-38.
https://www.doi.org/10.1053/j.gastro.2009.01.052
http://www.ncbi.nlm.nih.gov/pubmed/19208358?tool=bestpractice.com
The natural history of HDV infection is likely more severe than that of HBV infection alone and appears to be related to the degree of HDV replication.[18]Smedile A, Farci P, Verme G, et al. Influence of delta infection on severity of hepatitis B. Lancet. 1982 Oct 30;2(8305):945-7.
http://www.ncbi.nlm.nih.gov/pubmed/6127458?tool=bestpractice.com
[68]Fattovich G, Giustina G, Christensen E, et al. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep). Gut. 2000 Mar;46(3):420-6.
https://www.doi.org/10.1136/gut.46.3.420
http://www.ncbi.nlm.nih.gov/pubmed/10673308?tool=bestpractice.com
[69]Manesis EK, Vourli G, Dalekos G, et al. Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study. J Hepatol. 2013 Nov;59(5):949-56.
http://www.ncbi.nlm.nih.gov/pubmed/23850875?tool=bestpractice.com
An Italian study followed 299 patients with chronic HDV infections for almost 30 years and noted that 46 patients (15.4%) developed HCC, 43 (14.4%) developed ascites, 63 (21.1%) died, and 29 (9.7%) received liver transplantation. HDV replication was the only independent predictor of mortality.[18]Smedile A, Farci P, Verme G, et al. Influence of delta infection on severity of hepatitis B. Lancet. 1982 Oct 30;2(8305):945-7.
http://www.ncbi.nlm.nih.gov/pubmed/6127458?tool=bestpractice.com
Similar findings were noted in a Greek study of almost 5000 patients with chronic HBV infection. Patients with a positive anti-HDV (4.2%) had more active and advanced disease at baseline, were more likely to have cirrhosis at a younger age, and were more likely to develop a liver related event (20.0% vs. 8.5%) over a median follow-up of 4.2 years, compared with patients negative for anti-HDV.[69]Manesis EK, Vourli G, Dalekos G, et al. Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study. J Hepatol. 2013 Nov;59(5):949-56.
http://www.ncbi.nlm.nih.gov/pubmed/23850875?tool=bestpractice.com
After adjusting for clinical and serological differences, the increased risk of complications in patients with compensated cirrhosis with HDV/HBV co-infection compared with HBV infection alone were 3.2-fold for HCC, 2.2-fold for any decompensation, and 2.0-fold for mortality.[68]Fattovich G, Giustina G, Christensen E, et al. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep). Gut. 2000 Mar;46(3):420-6.
https://www.doi.org/10.1136/gut.46.3.420
http://www.ncbi.nlm.nih.gov/pubmed/10673308?tool=bestpractice.com
There are some geographical differences in the risk of complications, with studies in Taiwan, where genotype 2 HDV predominates, suggesting that the risk of fulminant liver failure and cirrhosis or HCC is decreased compared with genotype 1 disease (found mainly in North America, Europe, the Middle East, and north Africa).[7]Wu JC, Choo KB, Chen CM, et al. Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D. Lancet. 1995 Oct 7;346(8980):939-41.
http://www.ncbi.nlm.nih.gov/pubmed/7564729?tool=bestpractice.com
[8]Wu JC, Chen TZ, Huang YS, et al. Natural history of hepatitis D viral superinfection: significance of viremia detected by polymerase chain reaction. Gastroenterology. 1995 Mar;108(3):796-802.
http://www.ncbi.nlm.nih.gov/pubmed/7875481?tool=bestpractice.com
Conversely, genotypes 1 and 3 (which predominate in South America) lead to more severe disease and genotype 5 is associated with better response to therapy.[5]Majeed NA, Hitawala AA, Heller T, et al. Diagnosis of HDV: from virology to non-invasive markers of fibrosis. Liver Int. 2023 Aug;43(suppl 1):31-46.
https://www.doi.org/10.1111/liv.15515
http://www.ncbi.nlm.nih.gov/pubmed/36621853?tool=bestpractice.com
[6]Casey JL, Brown TL, Colan EJ, et al. A genotype of hepatitis D virus that occurs in northern South America. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9016-20.
https://www.doi.org/10.1073/pnas.90.19.9016
http://www.ncbi.nlm.nih.gov/pubmed/8415646?tool=bestpractice.com