Hepatitis D natural history: Difference between revisions

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==Overview==
==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.
[[HDV]] is a defective [[virus]] that requires individuals to be previously, or concomitantly, [[infected]] with [[HBV]].  The clinical manifestations of [[HDV infection]] are similar to those of [[HBV]], including: [[fatigue]], [[lethargy]], [[nausea]], [[jaundice]], [[acholic stools]] and [[dark urine]].  The disease progresses throughout 4 phases: incubation period; preicteric phase; icteric phase; and convalescence phase.  [[Infection]] with [[HDV]] may occur at the time of infection with [[HBV]], in which case both acute type B and type D hepatitis may develop.  95% of these patients will clear the [[infection]].  [[HDV]] may also infect a previous [[HBV]] carrier, often causing [[fulminant hepatitis]] and chronic active hepatitis, frequently progressing to [[cirrhosis]].  Complications of [[hepatitis D]] may include: chronic active hepatitis; [[fulminant hepatitis]]; [[hepatic cirrhosis]] and [[hepatic failure]]. The [[mortality rate]] for [[HDV infection]] is higher than that of [[hepatitis B]], between 2% and 20%.


==Natural History==
==Natural History==
HDV requires an associated HBV infection. 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]] lasting 3 to 7 days. [[ALT]] and [[AST]] levels elevate 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 elevate. [[Fatigue]] and [[nausea]] continue to be present. In patients with acute, self-limiting infection, '''convalescence''' begins with the disappearance of clinical symptoms. <ref name="WHO">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref>
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.<ref name="WHO">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref>


[[fulminant hepatitis|Fulminant viral hepatitis]] is rare, however, its [[mortality rate]] may reach 80%, and it is about 10 times more common in [[hepatitis D]] than in other types of [[viral hepatitis]]. It is characterized by:<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref>{{cite book | last = Fields | first = Bernard | title = Fields virology | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2013 | isbn = 1451105630 }}</ref>
[[fulminant hepatitis|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:<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref>{{cite book | last = Fields | first = Bernard | title = Fields virology | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2013 | isbn = 1451105630 }}</ref>
*[[Hepatic encephalopathy]] showing changes in personality
*[[Hepatic encephalopathy]]
*[[Sleep disturbances]]
*[[Sleep disturbances]]
*[[Confusion]]
*[[Confusion]]
Line 18: Line 18:
*[[Coma]]
*[[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]].<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref>{{cite book | last = Fields | first = Bernard | title = Fields virology | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2013 | isbn = 1451105630 }}</ref>


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 onset of [[infection]]. Many of these patients die of [[hepatic failure]].<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref>{{cite book | last = Fields | first = Bernard | title = Fields virology | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2013 | isbn = 1451105630 }}</ref>
===Coinfection===
[[Coinfection]] with [[HBV]] and [[HDV]] results in both acute type B and type D hepatitis. The [[incubation period|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]].<ref name="GAR">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref><ref name="pmid21511329">{{cite journal| author=Hughes SA, Wedemeyer H, Harrison PM| title=Hepatitis delta virus. | journal=Lancet | year= 2011 | volume= 378 | issue= 9785 | pages= 73-85 | pmid=21511329 | doi=10.1016/S0140-6736(10)61931-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21511329  }} </ref>
 
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]].<ref name="GAR">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref><ref name="pmid21511329">{{cite journal| author=Hughes SA, Wedemeyer H, Harrison PM| title=Hepatitis delta virus. | journal=Lancet | year= 2011 | volume= 378 | issue= 9785 | pages= 73-85 | pmid=21511329 | doi=10.1016/S0140-6736(10)61931-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21511329  }} </ref>


===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.<ref name="GAR">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref> 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]].<ref name="pmid6873613">{{cite journal| author=Farci P, Smedile A, Lavarini C, Piantino P, Crivelli O, Caporaso N et al.| title=Delta hepatitis in inapparent carriers of hepatitis B surface antigen. A disease simulating acute hepatitis B progressive to chronicity. | journal=Gastroenterology | year= 1983 | volume= 85 | issue= 3 | pages= 669-73 | pmid=6873613 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6873613  }} </ref>


===Coinfection===
[[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 these cases 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]].<ref name="GAR">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref>
[[Coinfection]] of [[HBV]] and [[HDV]] results in both acute type B and acute type D hepatitis. The [[incubation period|incubation]] depends on the [[HBV]] titer of the infecting [[inoculum]]. One or two bouts of hepatitis may be seen depending on the relative titers of [[HBV]] and [[HDV]]. 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 the 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]].<ref name="GAR">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref><ref name="pmid21511329">{{cite journal| author=Hughes SA, Wedemeyer H, Harrison PM| title=Hepatitis delta virus. | journal=Lancet | year= 2011 | volume= 378 | issue= 9785 | pages= 73-85 | pmid=21511329 | doi=10.1016/S0140-6736(10)61931-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21511329  }} </ref>


===Superinfection===
Although it is associated with a higher rate of [[cirrhosis]], a concomitant increase in the rate of [[HCC]] was not noted, possibly due to the suppression of [[HBV]] [[replication]], caused by [[HDV]].<ref name="pmid18098143">{{cite journal| author=Cross TJ, Rizzi P, Horner M, Jolly A, Hussain MJ, Smith HM et al.| title=The increasing prevalence of hepatitis delta virus (HDV) infection in South London. | journal=J Med Virol | year= 2008 | volume= 80 | issue= 2 | pages= 277-82 | pmid=18098143 | doi=10.1002/jmv.21078 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18098143  }} </ref>
[[HBV]] and [[HDV]] [[superinfection]] (HDV infection of a chronically infected HBV carrier) frequently causes a severe acute hepatitis with a short [[incubation period|incubation]] time. In the majority of cases, this leads to chronic type D hepatitis. [[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 often misdiagnosed as acute [[HBV]] or as chronic [[HBV]] causing a worsening of the [[liver disease]].<ref name="GAR">World Health Organization. Department of Communicable Disease Surveillance. Hepatitis Delta 2001. http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf</ref>


==Complications==
==Complications==
 
Common [[complications]] of [[hepatitis D]] include:<ref name="pmid21511329">{{cite journal| author=Hughes SA, Wedemeyer H, Harrison PM| title=Hepatitis delta virus. | journal=Lancet | year= 2011 | volume= 378 | issue= 9785 | pages= 73-85 | pmid=21511329 | doi=10.1016/S0140-6736(10)61931-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21511329  }} </ref>
*Chronic active hepatitis
*Chronic active hepatitis
*Fulminant hepatitis
*Fulminant hepatitis
*[[Hepatic cirrhosis]]
*[[Hepatic cirrhosis]]
*[[Hepatic failure]]
*[[Hepatic failure]]
*[[Hepatocellular carcinoma]]
 
===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]].<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref>
*[[HCC]] may be considered more a secondary effect of the associated [[cirrhosis]] than a direct [[carcinogenic]] effect of the [[HDV|virus]], however further studies are required to evaluate this relationship.<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref name="pmid23242761">{{cite journal| author=Heidrich B, Manns MP, Wedemeyer H| title=Treatment options for hepatitis delta virus infection. | journal=Curr Infect Dis Rep | year= 2013 | volume= 15 | issue= 1 | pages= 31-8 | pmid=23242761 | doi=10.1007/s11908-012-0307-z | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23242761  }} </ref><ref name="pmid19208358">{{cite journal| author=Romeo R, Del Ninno E, Rumi M, Russo A, Sangiovanni A, de Franchis R et al.| title=A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. | journal=Gastroenterology | year= 2009 | volume= 136 | issue= 5 | pages= 1629-38 | pmid=19208358 | doi=10.1053/j.gastro.2009.01.052 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19208358  }} </ref><ref name="pmid20546496">{{cite journal| author=Buti M, Homs M, Rodriguez-Frias F, Funalleras G, Jardí R, Sauleda S et al.| title=Clinical outcome of acute and chronic hepatitis delta over time: a long-term follow-up study. | journal=J Viral Hepat | year= 2011 | volume= 18 | issue= 6 | pages= 434-42 | pmid=20546496 | doi=10.1111/j.1365-2893.2010.01324.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20546496  }} </ref><ref name="pmid22423008">{{cite journal| author=Ji J, Sundquist K, Sundquist J| title=A population-based study of hepatitis D virus as potential risk factor for hepatocellular carcinoma. | journal=J Natl Cancer Inst | year= 2012 | volume= 104 | issue= 10 | pages= 790-2 | pmid=22423008 | doi=10.1093/jnci/djs168 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22423008  }} </ref>


==Prognosis==
==Prognosis==
The [[mortality rate]] for [[HDV]] [[infections]] is between 2% and 20%. These values are ten times higher than those of [[hepatitis B]].<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref>


Persons with an acute HDV infection usually get better over 2 to 3 weeks. Liver enzyme levels return to normal within 16 weeks. About 10% of those who are infected may develop long-term (chronic) liver inflammation (hepatitis).
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]].<ref>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.</ref>
 
Exposure to hepatitis D may worsen the symptoms of [[hepatitis B]]. Patients with co-infection are more likely to have fulminant hepatitis than those patients with HBV infection alone.
 
When acute infection with HDV occurs in the face of an existing chronic HBV infection, especially in persons with progressive, symptomatic chronic disease, there is increased progression of [[hepatic cirrhosis]] and [[hepatic failure]]. Both co-infection of hepatitis D and hepatitis B, as well as superinfection of hepatitis D, have been associated with fulminant hepatitis. Hepatitis D results in death in between 2 and 20 percent of patients with acute icteric hepatitis.<ref>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.</ref>


==References==
==References==
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{{reflist|2}}
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Latest revision as of 22:06, 29 July 2020

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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

HDV is a defective virus that requires individuals to be previously, or concomitantly, infected with HBV. The clinical manifestations of HDV infection are similar to those of HBV, including: fatigue, lethargy, nausea, jaundice, acholic stools and dark urine. The disease progresses throughout 4 phases: incubation period; preicteric phase; icteric phase; and convalescence phase. Infection with HDV may occur at the time of infection with HBV, in which case both acute type B and type D hepatitis may develop. 95% of these patients will clear the infection. HDV may also infect a previous HBV carrier, often causing fulminant hepatitis and chronic active hepatitis, frequently progressing to cirrhosis. Complications of hepatitis D may include: chronic active hepatitis; fulminant hepatitis; hepatic cirrhosis and hepatic failure. The mortality rate for HDV infection is higher than that of hepatitis B, between 2% and 20%.

Natural History

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]

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 these cases 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, possibly due to the suppression of HBV replication, caused by HDV.[7]

Complications

Common complications of hepatitis D include:[5]

Hepatocellular Carcinoma

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. ↑ 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
  2. ↑ Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1451105630.
  3. ↑ Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1451105630.
  4. ↑ 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. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.

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