CHAPTER 3: HEPATITIS D or Delta

 

In 1977 an Italian immunologist named Mario Rizzetto discovered a distinct immunological antigen-antibody system in the nuclei of the liver cells, in a patient with hepatitis B.  He decided it was a distinct virus and named it delta hepatitis. 

Delta, it turned out, is the smallest viral pathogen that infects humans.  It’s genome is a circular, single-strand of 1700 RNA nucleotides.. "The combination of HDV and HBV infection often causes a severe form of chronic viral hepatitis, and can cause liver-related death and hepatocellular carcinoma."

In the 25 years since it was recognized, eight genotypes have been identified.  Genotype 1, the most widely distributed, predominates in Europe and North America.

Genotype 3, present only in the Amazon basin, has been associated with outbreaks of fulminant hepatitis D, and the disease caused genotype 5 in Africa tends to be more benign and responds better to interferon than genotype 1.”

Worldwide the virus affects nearly 5% of people who have a chronic hepatitis B infection.   Some cases of chronic hepatitis D infection are the result of a situation where people with chronic hepatitis B are later infected with D.  Other cases occur when people are infected with a B virus that is already infected with delta.

(The virus was also discovered in 1977 in patients with chronic Hepatitis B virus (HBV) infection and was characterized .by Dr. Houghton when he was looking for the C virus at Chiron.)

Worldwide, the number of HDV infections has decreased since the 1980s, due mainly to a successful global HBV vaccination program.” 

In one study that lasted 1 to 15 years, histological deterioration was documented in 77% of Italian patients who were positive for anti-HDV antibodies, as compared with 30% of HBsAg carriers who did not have anti-HDV antibodies.   

In another study, HDV infection increased the risk of hepatocellular carcinoma by a factor of 3. And in another group  “75% of those with chronic hepatitis D develop liver cirrhosis within 15 years and had a much higher risk of developing liver cancer.”   

Chronic infection with hepatitis delta virus (HDV) affects between 12-20 million people worldwide

The hepatitis D virus (HDV), uses the surface proteins of the hepatitis B virus (HBV) as a vehicle to specifically enter liver cells. 

In recent years most American kids were vaccinated for B at birth.  Most adults weren’t.  Hepatitis B and D are usually acquired sexually or by drug injection but-- before you travel to Africa, Mongolia, the Amazon—or a number of other places--make sure you once had and fully recovered from hepatitis B--or that you were vaccinated for hepatitis B.  

For years the only treatment we had for D hepatitis was interferon, and it didn't work that well.  A recent study investigated the effect of a combination of the viral entry inhibitor bulevirtide 2 mg and 10 mg with and without PegIFN.  

Peg interferon alone worked in 17%  

2 mg bulevirtide worked in 32 % treated                

10m buleviride plus interferon worked in 46% 

--In a 48 week trial of 2mg and 10 mg of bulevirtide

The HDV RNA level at week 48 was undetectable in 12% in the 2-mg group

20% in the 10-mg group

The ALT level normalized in 12% of patients in the control group,

51% in the 2-mg group

56% in the 10-mg group

Loss of hepatitis B virus surface antigen (HBsAg) or an HBsAg level that decreased by at least 1 log10 IU per milliliter did not occur by week 48.

Headache, pruritus, fatigue, eosinophilia, injection-site reactions, upper abdominal pain, arthralgia, and asthenia were more common in the 2-mg and 10-mg groups combined than in the control group. No treatment-related serious adverse events occurred.

https://www.nejm.org/doi/full/10.1056/NEJMoa2213429

 

World Health Organization.https://www.who.int/news-room/fact-sheets/detail/hepatitis-d  

World Health Organization.https://www.who.int/news-room/fact-sheets/detail/hepatitis-d  

The, study was published in the New England Journal of medicine. Authors: Tarik Asselah, M.D and Mario Rizzetto, M.D. Published July 5, 2023 New England Journal of Med 2023;389:58-70

https://www.nejm.org/doi/full/10.1056/NEJMra2212151

https://www.nejm.org/doi/full/10.1056/NEJMra2212151\Hepatitis D Virus Infection: Pathophysiology, Epidemiology and Treatment. Report from the first International Delta Cure Meeting 2022  June 2023

Hepatitis D Virus Infection Tarik Asselah, M.D. https://orcid.org/0000-0002-0024-0595, and Mario Rizzetto, M.D. Published July 5, 2023 N Engl J Med 2023;389:58-70    https://www.ncbi.nlm.nih.gov/books/NBK470436/#:~:text=Hepatitis%20D%20virus%20(HDV)%20was,known%20as%20the%20delta%20agent


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