HDV Superinfection Research Articles

HCV, HIV, HBV and HDV infections in intravenous drug addicts.

Hepatitis viruses and the acquired immunodeficiency viruses often infect intravenous drug addicts (IVDAs). Our study includes 255 IVDAs (26 females and 229 males, aged 20-35 years) from Cagliari. Of 255 subjects examined, 207 (81.1%) were positive for anti-HCV and 84 (32.9%) for anti-HIV. Nineteen (7.4%) subjects were HBsAg carriers, and 12 of these (63%) had an HDV superinfection. Markers of previous HBV infections were tested in 223 cases and 137 (61.4%) were found positive; of these 14 (10.2%) also had HDV infection. Of the 223 drug addicts examined for all infection markers, 18 (8%) were negative to all markers, 46 (20.6%) were positive to only one, 89 (39.9%) were positive to two, 64 (28.7%) to three and 6 (2.6%) were positive to all. Subjects with a single infection were significantly fewer than those with multiple infections. The correlations studied among the various markers did not point out any statistically significant associations. Even so, a previous HBV infection was more common while active HBV/HDV infections were less common among subjects with anti-HCV; HDV infection was more common among HIV-positive subjects. In HBsAg carriers neither HBV-DNA nor HCV-RNA was detected; HCV-RNA was found more frequently in anti-HIV positive subjects than in subjects with the anti-HCV isolate.

Role of hepatitis delta virus infection in hepatocellular carcinoma.

Hepatitis B virus (HBV) DNA integrates into the host DNA and shows a series of potentially oncogenetic properties, but HBV is not an acutely transforming virus, because HCC develops decades after infection. Other factors, namely cirrhosis, inflammation, alcohol intake, and viral superinfections, could promote the oncogenetic process induced by HBV-DNA integration. We studied the impact of HDV infection in the pathogenesis of HCC in 62 consecutive patients. Their mean age was 59 years (range 25-75 years), 54 were male and eight female; 58 had cirrhosis. The findings suggest that HBsAg-positive patients with HDV superinfection developed cirrhosis and HCC at an earlier age than HBsAg carriers without HDV infection. HDV appears to represent a "promotion" factor for HCC in subjects with an oncogenic risk induced by HBV. A long-lasting necroinflammatory lesion of the liver substained by productive HBV and HDV infections may be a major pathogenetic mechanism.

Chronic Evolution of Acute Hepatitis B: The Significance of Simultaneous Infections with Hepatitis C and D

Seventy-six of 77 consecutive patients with hepatitis B surface antigen (HBsAg)-positive acute hepatitis were reevaluated using anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), and IgM anti-hepatitis B core (HBc) testing. Anti-HCV and/or anti-HDV was found in 32 patients (42%). The presence of these markers was significantly associated with intravenous drug abuse (p less than 10(-6). Sixty-nine patients were IgM anti-HBc-positive, of whom two (3%) (95% confidence limits, 1-12%) became chronic HBsAg carriers with histologically verified chronic liver disease; both were anti-HCV and anti-HDV-negative. Among the remaining 67 IgM anti-HBc-positive patients 8 had HBV and HDV co-infection, 3 had HBV and HCV co-infection, and 1 had HBV, HCV, and HDV co-infection. Twenty-two had evidence of preceding or past HCV infection; two developed chronic active hepatitis in spite of HBsAg clearance. Seven patients with IgM anti-HBc negative. One was a chronic HBsAg carrier with HDV superinfection. One had subclinical acute HBV infection and became a chronic HBsAg carrier. In a further two patients reactivation of replication in a chronic HBV infection could not be disregarded. Three patients could not be classified; all had acute recent onset of symptoms, cleared HBsAg within 6 months, but lacked IgM anti-HBc. It is concluded that HCV and HDV superinfections in HBV carriers mimicking acute HBV infection with chronic evolution are rarely encountered in the present population in spite of high frequency of both HCV and HDV markers.

Hepatitis B virus clearance from serum and liver after acute hepatitis delta virus superinfection in chronic HBsAg carriers

Clinical, virological, and histological findings in four HBsAg chronic carriers who cleared HBV markers from both serum and liver following HDV superinfection are described. The patients were long-term HBsAg carriers and all were HBV-DNA/HBeAg positive. Liver biopsy, obtained from three of the patients between 5 and 15 months prior to HDV superinfection, showed chronic persistent hepatitis in two and chronic active hepatitis in one. During the follow-up of 9-19 months, the patients completely recovered from acute delta hepatitis with termination of HBsAg carriage and regression of the histological feature of chronic liver damage. These data demonstrate that sometimes HDV is able to induce a permanent inhibition of its helper virus. HDV superinfection probably enhances the immune clearance of infected cells during the replicative phase of chronic HBV infection.

HEPATITIS B LIVER DISEASE IN CYCLOSPORINE-TREATED RENAL ALLOGRAFT RECIPIENTS

To establish the impact of cyclosporine on the development of chronic hepatitis in hepatitis B surface antigen (HBsAg)-positive renal allograft recipients, the incidence and outcome of chronic hepatitis in 20 cyclosporine-treated patients (CsA group) were compared with 13 azathioprine-treated patients (AZA group). All 33 patients had a functioning graft for 2 years or longer. Twenty-nine of the 33 patients were HBsAg-positive prior to the initiation of hemodialysis. The difference in the incidence of chronic hepatitis between these 2 groups was not statistically significant (78.6% in the AZA group vs. 52.4% in the CsA group, P = 0.12). In the CsA group, 3 patients (15%) developed liver cirrhosis, and there was a 5% mortality. The AZA group had a 7.7% mortality, and 4 patients (30.8%) developed liver cirrhosis. Serial serum samples obtained from these 33 HBsAg-positive renal allograft recipients were analyzed for antibody to hepatitis D virus (anti-HD). Anti-HD was found in 3 patients. Two of them developed anti-HD seroconversion after renal transplantation during a mean follow-up of 4 years. All 3 patients developed chronic hepatitis and 2 of them have subsequently developed liver cirrhosis. There was a mortality of 6.1% in 33 HBsAg-positive patients compared with a 5.3% mortality in 57 HBsAg-negative renal allograft recipients. The difference was not statistically significant. We conclude from this study that (1) CsA-treated HBsAg-positive renal allograft recipients have a tendency to develop chronic hepatitis like AZA-treated patients; (2) HBsAg-positive patients have an increased risk of HDV superinfection after renal transplantation, and this may result in rapid progression to liver cirrhosis; (3) HBsAg-positive patients who acquire HBsAg prior to renal transplantation have a low overall mortality, including death due to liver disease, for a mean follow-up of 4 years.

Type D (Delta) Hepatitis-Reply

In Reply.— Caredda et al are correct to point out that not all cases of acute HDV coinfection and superinfection will test positive for HBsAg. In HDV coinfection, HBsAg may have already disappeared by the time the patient is cared for. Furthermore, in HDV superinfection, HBsAg titers may fall transiently to undetectable levels. Thus, testing for antibody to HDV (anti-HDV) in HBsAg-negative patients may occasionally provide evidence of delta infection. In these situations, however, one does not know whether anti-HDV indicates recent or distant infection; more direct markers of delta replication (HDV RNA, HDV antigen, or IgM anti-HDV) would be better evidence that the acute hepatitis is caused by HDV. In this regard, recent evidence suggests that HDV does not require HBsAg for replication , but rather for entry and exit from the hepatocyte. Thus, in some cases of liver transplantation for delta hepatitis, HDV antigen or RNA in the absence

Liver HBV replication in HBsAg + patients with and without HDV superinfection

Liver HBV replication in HBsAg + patients with and without HDV superinfection

Hepatitis δ virus infection in India

Serological markers of hepatitis δ virus (HDV) and hepatitis B virus (HBV) infection were studied in 87 HBsAg positive patients, comprised of 18 patients with uncomplicated acute viral hepatitis (AVH), 34 patients with fulminant hepatic failure (FHF), 18 patients with subacute hepatic failure (SAHF) and 17 patients with chronic active hepatitis (CAH). The prevalence of HDV infection was found to be 27.8%, 20.6%, 16.7% and 11.8%, respectively in these four groups. Co‐infection of HDV and HBV was common amongst patients with AVH but superinfection by HDV in chronic HBV carriers was the predominant form of infection in patients with FHF, SAHF and CAH. HDV superinfection in these groups did not significantly alter the common tests of liver function or the DNA‐polymerase positivity.

Hepatitis D virus infection in children with acute or chronic hepatitis B virus infection in Taiwan

To investigate the prevalence and clinical features of hepatitis D virus infection (HDV) in childhood, total antibody to hepatitis D antigen (anti-HD) in serum samples from 247 children (29 with acute hepatitis B, 68 with chronic hepatitis B, and 150 with asymptomatic hepatitis B surface antigen (HBsAg) carriers with normal liver function profiles) were studied using solid-phase competitive radioimmunoassay. Anti-HD was detected in three of the 29 children with acute hepatitis B and in only one of the 68 with chronic hepatitis B; none of the serum specimens from 150 asymptomatic carriers with normal liver function profile showed detectable anti-HD. All three children with HDV coinfection cleared HBsAg and seroconverted to anti-HBs, whereas one with superinfection finally had normal liver function without clearance of HBsAg. To identify possible sources of HDV infection, HBV markers and anti-HD in family members were also examined. One 4-month-old infant boy became infected through a blood transfusion from his hepatitis B e antigen (HBeAg)-positive carrier father, who had anti-HD. A 4-month-old infant girl was infected through close contact with her HBeAg-negative carrier father, who had HDV superinfection. The infection sources remained undefined in another two patients. The mothers of these four children were seronegative for anti-HD, indicating that perinatal transmission is not the usual mode of HDV infection in Taiwan. The natural course of either acute or chronic HBV infections in childhood in Taiwan may be more closely related to HBV itself, or to some other yet unrecognized factor, rather than to HDV infection.

Beneficial effect of recombinant α 2A interferon in a patient with can due to recent HDV superinfection

Beneficial effect of recombinant α 2A interferon in a patient with can due to recent HDV superinfection

In vitro interleukin-2 and interleukin-2 receptor responses to alpha-interferon in HBsAg+ patients with and without HDV superinfection

In vitro interleukin-2 and interleukin-2 receptor responses to alpha-interferon in HBsAg+ patients with and without HDV superinfection

Recombinant α2c-interferon therapy in fulminant viral hepatitis

Recombinant alpha 2c-interferon was administered to 12 consecutive patients with fulminant viral hepatitis. The disease was caused by coinfection by HBV and HDV in seven patients, by HDV superinfection of a chronic HBV carrier in two, by HBV alone in two and by HAV in one. Eight patients were drug addicts. Interferon administration was initiated shortly after the onset of hepatic encephalopathy and no patient was in grade IV coma at the beginning of therapy. Ten patients died and only two survived. One of the survivors was an asymptomatic HBV carrier superinfected by HDV in whom treatment with interferon for 3 months did not prevent the development of chronic delta infection and liver cirrhosis. These results show that alpha 2c-interferon does not have significant therapeutic value in fulminant viral hepatitis, particularly if it is caused by HDV.

Therapeutic potential of acyclovir and of the interferons in HBV-related chronic active hepatitis due to HBV with or without HDV superinfection

Acyclovir only demonstrated activity in CAH patients with low HBV replication (DNA-p less than or equal to 80 cpm). In those, oral acyclovir 4 g/day for 4 months was able to permanently inhibit DNA-p in 5/5 cases without significant side-effects.