New epidemiology of hepatitis delta

Hepatitis D virus (HDV) is a defective pathogen that needs hepatitis B virus (HBV) for infection. Co‐infection of HBsAg‐positive individuals with HDV is commonly associated with a more rapid progression to cirrhosis, a higher incidence of hepatocellular carcinoma (HCC) and increased mortality. Initial studies have shown that about 5% of chronic HBV carriers worldwide (15‐20 millions) were also infected with HDV. However, recent studies suggest that the prevalence of HDV is at least two‐ to three‐fold higher than previous estimations. Improved diagnostic techniques have shown that HDV infection remains endemic in certain areas of the world. Injection drug users, individuals with high‐risk sexual behaviour and patients co‐infected with human immunodeficiency virus (HIV) represent the major reservoir of the disease in the Western world. Although the burden of HDV infection significantly decreased in Europe in the nineties, there has been no further decrease in the last decade, probably because of migration from HDV endemic countries. Until new and more effective therapies are available, public health measures should be reinforced by increasing prophylactic HBV vaccination programs, preventing transmission of the virus among parenteral drug users and implementing universal HDV screening of all HBV‐infected individuals.     

Nosocomial transmission of delta hepatitis

A previously asymptomatic carrier of hepatitis B virus receiving chronic hemodialysis developed acute delta hepatitis. The patient regularly received dialysis treatments on the same machine as a parenteral drug abuser with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis whose serum was strongly positive for delta antibody. The drug abuser had a major bleeding episode that caused extensive environmental contamination 3 months before onset of illness in the index patient. No other patients receiving dialysis or staff members had evidence of delta infection. A surgeon previously infected with hepatitis B from the same parenteral drug abuser also had delta antibody. Testing for delta virus is indicated for both HBsAg-positive parenteral drug abusers and patients with hemophilia receiving chronic hemodialysis. All patients who are HBsAg- and delta-positive should receive dialysis separately from patients who are HBsAg-positive and delta-negative. Susceptible patients on dialysis and staff should receive hepatitis B vaccine to protect against both hepatitis B and delta virus infection.     

Serologic diagnosis and epidemiology of acute delta hepatitis in Indre-et-Loire

A 6 years retrospective study (1981-1986) of 153 consecutive cases of HBsAg positive acute hepatitis was carried out to assess the prevalence of delta virus infections in the Indre-et-Loire a district of the Loire Valley in France. Diagnostic value of the various serum markers of delta infection, i. e. HDAg, anti-HD and anti-HD IgM, were evaluated using immunoenzyme assays. During the survey, 22 cases of delta hepatitis were diagnosed (12 co-infections, 10 superinfections). They all involved young adults, 21 of them were drug-addicts, and one young woman was the consort of a drug-addict. In Indre-et-Loire, delta virus infection was responsible for half of acute HBsAg positive hepatitis among drug-users in the last 3 years of our study. Clinical and biological features of acute delta hepatitis were compared to those of the other HBsAg positive hepatitis: two cases of fulminant hepatitis occurred among the 12 co-infections; 4 of 6 superinfection that could be followed up to 6 months developed biopsy-proven chronic active hepatitis. Delta Ag was found constantly during the first week of the disease, its disappearance was always followed by a seroconversion to anti-HD after four weeks. Anti-delta IgM was an inconstant and late marker: it was detected within the first 4 weeks in only one case (a co-infection); it persisted only in superinfections. Our study shows that delta Ag is an efficient serum marker for the early diagnosis of acute delta hepatitis.     

Intrafamilial transmission of hepatitis delta virus: molecular evidence

BACKGROUND/AIMS: Epidemiologic studies have suggested that transmission of hepatitis delta virus (HDV) occurs by intrafamilial routes in some populations in southern Italy, where HDV infection is endemic. To further evaluate intrafamilial transmission of HDV, we obtained the partial sequence of the viral genome from HDV-RNA positive members of families in which two or more immediate family members were positive for HDV-RNA. METHODS: The region analyzed was the semi-conserved region from nucleotides 908 to 1265. Sequences obtained from family members were compared with those obtained from a control group of 20 unrelated patients. RESULTS: The mean genetic divergence among HDV isolates was 2.8 +/- 1.7% within the 9 families analyzed, and 7.6 +/- 2.2% among the control group of unrelated individuals (p < 0.0001). A Receiver Operating Characteristic curve and Youden Index were used to define a cut-off value of 3.5% to discriminate sequence variations calculated within families and in the control group. CONCLUSIONS: The data indicate that in most family units, HDV-infected members harbored nearly identical strains of HDV, and provide molecular support that HDV infection can be transmitted within the family. Such spreading among family members highlights the role of inapparent transmission through personal contacts.     

HCV: epidemiology, modes of transmission and prevention of spread.

Approximately 3% of the world's population has been infected with the hepatitis C virus (HCV), which represents about 170 million chronic carriers at risk of developing serious complications. Following the introduction of screening of blood donors for infection the risk of transmitting HCV by blood products is presently at 1/200,000 units distributed. Intravenous (i.v.) drug users are currently the main risk group with a prevalence rate of about 80% and a yearly incidence varying between 4 and 6%. Vertical and sexual transmissions have also been implicated but data are limited and sometimes controversial. The source of infection for the 30% of cases without an identifiable risk factor remains to be clarified. Prevention of spread includes detailed information of persons at risk of being infected, screening of high-risk populations, strengthening of syringe exchanges among i.v. drug users and strict application of disinfection procedures for all invasive medical equipment.     

The epidemiology of hepatitis delta infection in Italy. Promoting Group.

The epidemiology of HDV infection in Italy was assessed in a retrospective study involving 1556 HBsAg chronic carriers on their first presentation at one of the 35 Liver Units in 1987. Total anti-HD was detected in 23.4% of HBsAg carriers and was significantly more frequent in southern than in northern Italy (26.6% vs. 19.1%, p less than 0.01). Age distribution showed that 73% of the anti-HD-positive subjects, but only 56% of the anti-HD-negative subjects, were under 40 years of age (p less than 0.01). Anti-HD prevalence increased with the severity of the liver disease from 3.8% in healthy carriers to 42.5% in cirrhosis. No geographical statistical difference was found among HBsAg healthy carriers or subjects with chronic persistent hepatitis (CPH), while among patients with chronic active hepatitis (CAH) or cirrhosis anti-HD prevalence was much higher in the south (p less than 0.01). The various potential risk factors were evaluated by multiple logistic regression analysis. HDV infection was independently related to young age, residence in the south, i.v. drug abuse, a large family and household contact with an anti-HD-positive carrier. No association was found with blood transfusion or male homosexuality. These findings confirm that HDV infection is endemic in Italy, particularly in some southern areas, where intrafamily contact probably at a young age may favour the spread of the infection.     

Worldwide epidemiology of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) continues to cause a heavy health and economic burden around the world. Recent studies have added evidence to the etiologic role of known and suspected risk factors for lung function decline and COPD, including smoking, occupational exposures, air pollution, airway hyperresponsiveness, and certain genetic variations. Among most populations, COPD prevalence and mortality are still increasing and will likely continue to rise in response to increases in smoking, particularly by women and adolescents. Resources aimed at smoking cessation and prevention and the early detection of COPD will be of the most benefit in our continuing efforts against this important cause of morbidity and mortality.     

The epidemiology and clinical outcome of hepatitis D virus (delta) infection in Jordan

The epidemiology and clinical outcome of hepatitis D viral infection in HBsAg-positive acute hepatitis, chronic liver disease, primary hepatocellular carcinoma and the symptomless carrier state was studied in Jordan. The prevalence of hepatitis D viral infection was significantly higher in patients with chronic liver disease (18/79, 23%) and acute hepatitis (17/108, 16%) than in symptomless HBsAg carriers (2/136, 2%). The highest prevalence of hepatitis D viral infection was found in patients with primary hepatocellular carcinoma (10/15, 67%) who were also significantly older than such patients without hepatitis D viral infection. Antihepatitis D virus IgM was detected persistently in 83% of patients with antihepatitis D virus-positive chronic liver disease and transiently in 41% of patients with acute hepatitis. A trend to increased mortality was observed in acute hepatitis D viral superinfection (25%) compared to hepatitis D viral coinfection (0%) and to antihepatitis D virus-negative HBsAg-positive acute hepatitis (4%). In patients with established chronic liver disease, however, neither survival nor histological parameters of disease activity were significantly different in the antihepatitis D virus-positive and antihepatitis D virus-negative groups. While the early stage of hepatitis D viral superinfection is associated with increased mortality, it appears that in patients with late-stage chronic liver disease, severe histological activity subsides, and survival is no longer influenced by the factor of hepatitis D viral infection. However, primary hepatocellular carcinoma appears to complicate the course of those antihepatitis D virus-positive patients surviving beyond this stage.     

Viroids and hepatitis delta virus

There is a subviral world, whose most prominent representatives are viroids. Despite being solely composed by a circular, highly structured RNA of ~250 to 400 nucleotides without protein-coding ability (all viruses code for one or more proteins), viroids can infect and incite specific diseases in higher plants. The RNA of human hepatitis delta virus (HDV), the smallest genome of an animal virus, displays striking similarities with viroids: It is circular, folds into a rodlike secondary structure, and replicates through a rolling-circle mechanism catalyzed by host enzymes and cis-acting ribozymes. However, HDV RNA is larger (~1700 nucleotides), encodes a protein in its antigenomic polarity (the ? antigen), and depends for transmission on hepatitis B virus. The presence of ribozymes in some viroids and in HDV RNA, along with their structural simplicity, makes them candidates for being molecular fossils of the RNA world that presumably preceded our extant world based on DNA and proteins.     

Worldwide epidemiology of liver hydatidosis including the Mediterranean area

The worldwide incidence and prevalence of cystic echinococcosis have fallen dramatically over the past several decades. Nonetheless, infection with Echinococcus granulosus (E. granulosus) remains a major public health issue in several countries and regions, even in places where it was previously at low levels, as a result of a reduction of control programmes due to economic problems and lack of resources. Geographic distribution differs by country and region depending on the presence in that country of large numbers of nomadic or semi-nomadic sheep and goat flocks that represent the intermediate host of the parasite, and their close contact with the final host, the dog, which mostly provides the transmission of infection to humans. The greatest prevalence of cystic echinococcosis in human and animal hosts is found in countries of the temperate zones, including several parts of Eurasia (the Mediterranean regions, southern and central parts of Russia, central Asia, China), Australia, some parts of America (especially South America) and north and east Africa. Echinococcosis is currently considered an endemic zoonotic disease in the Mediterranean region. The most frequent strain associated with human cystic echinococcosis appears to be the common sheep strain (G1). This strain appears to be widely distributed in all continents. The purpose of this review is to examine the distribution of E. granulosus and the epidemiology of a re-emerging disease such as cystic echinococcosis.     

Prevalence and epidemiology of autoimmune hepatitis

The incidence and characteristics of AIH differ in various geographic regions. Based on limited epidemiologic studies, the incidence of type 1 AIH among Caucasoid populations of Europe and North America ranges from 0.1 to 1.9/100,000/year. The disease is considerably less frequent in Japan. The relative proportion of AIH among cases with chronic hepatitis is low in regions with a high prevalence of viral hepatitis. Type 2 AIH is more frequent in southern Europe than in northern Europe, the United States, and Japan. The occurrence of anti-SLA/LP is also higher in European than in Japanese patients with type 1 AIH. The frequency of HLA markers that affect susceptibility to AIH varies between ethnic groups. DRB1*0301 (DR3) and DRB1*0401 (DR4) are the major risk factors for type 1 AIH in white European and North American populations. DRB1*0405 (DR4) is the principal risk factor in Japanese and adult Argentine patients with type 1 AIH, and DRB1*0404 (DR4) is the main susceptibility allele in Mestizo Mexicans. Children may have different clinical manifestations than adults, and the diagnoses of type 2 AIH, autoimmune sclerosing cholangitis, and APS1 should be considered. Uniform application of diagnostic criteria formulated by the International Autoimmune Hepatitis Group should strengthen future epidemiologic studies and extend awareness of AIH to yet unstudied minority groups.     

Treatment of chronic delta hepatitis

Chronic delta hepatitis (CDH) remains the most progressive form of chronic viral hepatitis and as such its successful treatment is important. However, in striking contrast to the situation in chronic hepatitis B and C, no new drugs for its treatment have been introduced in the recent past and interferons remain the only evidence-based effective treatment of CDH. However, results are far from optimal. Overall, around 25 to 30% of patients may have a sustained response after one year of conventional or pegylated interferon (Peg-INF) treatment and such treatment may favorably affect the natural history of the disease. The superiority of Peg-INF over its conventional form is possible, but has not been demonstrated in a clinical trial. Several unanswered questions remain in the context of INF treatment such as (1) the need for standardization of HDV-RNA quantitation, the most widely used surrogate marker of treatment efficacy; (2) validation of this treatment end point as an index of long-term containment of HDV; (3) optimal duration of treatment; (4) baseline and on-treatment parameters of treatment efficacy; and (5) development of new markers of treatment efficacy. Nucleos(t)ide analogs (NAs) have been widely tested in CDH, but they appear to be ineffective when used for a duration of up to 2 years. Combination treatment of NAs with INFs also proved to be disappointing. New approaches to treatment are hepatocyte entry inhibitors and prenylation inhibitors to be hopefully tested in human CDH in the not-too-distant future.     

Serum hepatitis delta virus RNA in patients with delta hepatitis and in liver graft recipients

We have investigated the usefulness of serum hepatitis delta virus (HDV) RNA detection using a slot hybridization analysis of serum samples from ten patients with acute hepatitis and delta markers (group I), from 28 patients with chronic delta hepatitis (group II) and from seven liver graft recipients with hepatitis B virus (HBV) and HDV related cirrhosis or fulminant hepatitis (group III). The slot-blots were hybridized with both HDV-complementary DNA and single-stranded RNA probes. With the single-stranded RNA probe, HDV RNA was detected in the first serum sample available in 9/10 of the patients with acute hepatitis (group I). In addition, HDV RNA was detected in 8/9 and 7/8 of the samples obtained within and after 1 month of the onset of hepatitis. Five of the ten patients scored positive for HDV RNA and negative for hepatitis delta antigen (HDAg) while one was negative for HDV RNA and positive for HDAg. The same RNA probe enabled the detection of serum HDV RNA in 21/28 chronic hepatitis patients (liver HDAg and/or IgM anti-HD positive) (group II). Among the liver graft recipients (group III), 7/7 had a recurrent delta infection. Serum HDAg, liver HDAg and anti-HD IgM were identified in 3/7, 6/7 and 5/7 of the patients, respectively. HDV RNA was detected in the seven patients with either persistent (4/7) or transient (3/7) positivity. In addition, HBsAg and HBV RNA were persistently shown in 4/7 patients with continuous HDV replication. In the remaining three patients, HDV RNA was detectable despite the absence of HBsAg.(ABSTRACT TRUNCATED AT 250 WORDS)