Etiology

The hepatitis D virus (HDV), initially called the delta agent and then the hepatitis delta virus, was first described in 1977 as a pathogen that superinfects some patients already infected with HBV. Persons with acute or chronic HBV infection, as demonstrated by serum HBsAg, can be infected with HDV. HBV is required as a so-called helper to initiate infection.

The HDV is a replication defective or incomplete RNA virus that by itself, is unable to cause infection. HDV consists of a single-stranded, circular RNA coated in HBsAg. HDV is interesting because it can force the host’s RNA polymerase to transcribe the HDV RNA genome.

Epidemiology

 Hepatitis D was originally described in Italy and appears to be most common in southern European countries. It also appears to be endemic among Indian tribes living in the Amazon basin. In the United States, Northern Europe, and Asia, infection is uncommon. In the United States, hepatitis D is seen predominantly in intravenous (IV) drug users and their sexual partners, but it has been reported in homosexual men and men with hemophilia. According to the Centers for Disease Control and Prevention (CDC), there are approximately 70,000 people with chronic HDV infection in the United States.

Hepatitis D is a severe and rapidly progressive liver disease for which no therapy has proven effective. Patients with this form of hepatitis are significantly more likely to have cirrhosis and liver failure and to require liver transplantation than patients with HBV infection alone. Chronic HDV infection is responsible for more than 1000 deaths/year in the United States. The mortality rate can be up to 20% of infected patients.

Hepatitis D virus is spread chiefly by direct contact of HBsAg carriers with HDV- or HBV-infected individuals. Family members and intimate contacts of infected individuals are at greatest risk. IV drug users and individuals with multiple sex partners are two other high-risk groups. Maternal-neonatal transmission is uncommon.

Hepatitis D can be acquired either as a co–primary infection (coinfection) with HBV (e.g., after inoculation with blood or secretions containing both agents) or as a superinfection in patients with established HBV infection (HBsAg carriers or patients with chronic hepatitis B). A superinfection can make an HBV infection worse by transforming a mild infection into a persistent infection in 80% of patients. In contrast, coinfection rarely leads to a chronic condition. Although HDV is dependent on HBV for its expression and pathogenicity, replication of HDV appears to be independent of the presence of its associated hepadnavirus.

Signs and Symptoms

Hepatitis D infection may be benign and brief, but fulminant hepatitis and chronic hepatitis have been attributed with increasing frequency to HDV. Chronic HDV infection is associated with increased hepatic damage and a more severe clinical course than is expected from chronic HBV infection alone. The occurrence of sequential attacks of HBV in the same patient is probably attributable in most cases to HDV infection superimposed on a previous acute HBV infection.

Infection with HDV agent can occur in several conditions; the symptoms would be typical of acute or chronic hepatitis, as follows:

• Acute hepatitis D with concurrent acute hepatitis B (coinfection)

 • Acute hepatitis D in a chronic HBsAg carrier

• Chronic hepatitis D in a chronic HBsAg carrier

Immunologic Manifestations

The HDV probably partially suppresses HBV replication. Hepatitis D infection is diagnosed by the appearance of HDV antigen in serum or the development of IgM or IgG HDV antibodies that appear sequentially in a time frame similar to that described for hepatitis A or B antibodies. HBsAg will also be present.

Coinfection With Hepatitis B Virus

In patients with acute, self-limited HDV coinfection with HBV, various serologic responses indicative of HDV infection have been identified. Serum HDV RNA and HDV antigen (HDAg) may be detected early, concurrently with the detection of HBsAg. HDAg disappears as HBsAg disappears and seroconversion to anti–hepatitis D (anti-HD; initially, IgM and later IgG) follows. The IgM reactivity usually appears several days to a few weeks after the onset of illness, whereas IgG anti-HD appears in the convalescent phase. In about 60% of coinfections, HDAg is not detected by anti-HD, but patients can manifest both IgM and IgG antibodies. IgM anti-HD in self-limited coinfections is usually transient. IgG anti-HD often disappears as well, but occasionally persists in declining titer for many months and may remain detectable as long as 1 to 2 years after the disappearance of HBsAg. In a small number of patients, the early appearance of isolated IgM anti-HD, or its appearance during convalescence of isolated IgG anti-HD, may be the only detectable marker of HDV infection.

Superinfection of Hepatitis B Carrier

Hepatitis D superinfection of HBV (HBsAg) carriers causes the appearance of HDAg and HDV RNA, a simultaneous reduction in HBV replication, and a consequent diminution in the titer of circulating HBsAg. Termination of the HBsAg carrier state appears to occur infrequently after HDV inhibition of HBV replication. Often, HDV infection becomes chronic and HDAg and HDV RNA may remain detectable at low levels in the serum; in persistent HDV infection, large quantities of HDAg can be detected in hepatocytes. High titers of IgM and IgG anti-HD are maintained in persistent infection, reflecting progressive, HDV-induced, chronic liver disease.

Diagnostic Evaluation

The HDV appears in the circulating blood as a particle with a core of delta antigen and a surface component of HBsAg. A person with hepatitis D will have detectable antigen in the liver and antibody in the serum. Test methodologies for HDV use the qualitative EIA (Fig. 1)

Fig1. Hepatitis delta virus (HDV) testing algorithm. (From ARUP Laboratories: Hepatitis delta virus [HDV] testing algorithm, 2012 [http://www. arupconsult.com/Algorithms/HDV.pdf].)

In addition, HDV antigen can be demonstrated in liver biopsies by double immunodiffusion (DIF) and immunoperoxidase and in serum by cloned DNA (cDNA). The importance of the detection of antibodies to HDV is largely prognostic. Detection of IgG anti-HDV in the presence of IgM anti-HBc antibody strongly suggests simultaneous infection (coinfection). Detection of IgM anti-HDV in a patient with chronic HBV infection is evidence of HDV superinfection.

Screening for total HDV antibodies in serum is important in the identification of a subpopulation of apparently healthy HBsAg carriers whose risk of serious liver damage is fourfold higher than that of anti-HDV–negative carriers. The combined presence of total anti-HDV antibody and abnormal liver function test results in a symptom-free carrier suggests parenchymal damage and is considered an indication for liver biopsy. Hepatic lesions in anti-HDV–positive carriers often consist of chronic active hepatitis or advanced cirrhosis. A positive test result for IgM anti-HDV increases the likelihood of occult active HBV infection.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم شؤون المعارف ينظم دورة متقدمة في تحقيق المخطوطات لملاكاته

قسم الشؤون الفكرية يصدر العدد العشرين من مجلة دراسات إفريقية

المجمَع العلمي يكرم الأساتذة المشاركين في مشروع الدورات القرآنية الصيفية في كربلاء

العتبة العباسية المقدسة تختتم فعاليات البرنامج المركزي الأسبوعي لمنتسبيها

المزيد

الآخبار الصحية

تحذير من "عدوى بكتيرية" تسبب نوبات قلبية

ماذا يحصل لجسمك عند التوقف عن استخدام الزيت في الطهي؟

الأمل في كبسولة.. "فيتامين شهير" يبطئ التقدم في العمر

اشتهاء أطعمة بشكل مفاجئ.. ناقوس خطر للسرطان ؟!

المزيد

الآخبار التكنلوجية

زلزال أفغانستان يحصد أكثر من ألف قتيل.. ويدمر آلاف المنازل !

ناجٍٍ وحيد من انزلاق أرضي.. دمّر قرية سودانية بأكملها !

نهر الفرات.. مورد مائي بين الندرة والتقاسم

ما السر وراء مشية إيلون ماسك الغريبة والسريعة ؟

المزيد

مواضيع ذات صلة

Pathogenesis and clinical significance of HIV

Transmission of HIV

HIV replication

Prevention and Treatment of hepatitis B

Differentiating Acute and Chronic Hepatitis and the Chronic Carrier State

Flaviviridae

Togaviridae

Caliciviridae

Picornaviridae

Laboratory Assays of Hepatitis B

Epidemiology of Hepatitis B

Hepatitis A