Seroepidemiological study of hepatitis delta virus infection in Okinawa, Japan

A seroepidemiological study on hepatitis delta virus (HDV) infection was conducted in the Okinawan islands, the area of Japan where hepatitis B virus infection is most prevalent. The subjects of this study included 116 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 48 patients with chronic hepatitis (CH), 19 with liver cirrhosis (LC), and 11 with hepatocellular carcinoma (HCC). Among the 194 serum samples examined, a total of 10 (5.2%) were anti-HDV seropositive. Anti-HDV was detected in 2 (1.7%) of the 116 asymptomatic HBsAg carriers, in 3 (6.3%) of the 48 patients with CH, and in 5 (26.3%) of the 19 with LC. However, none of the patients with HCC had detectable anti-HDV. Eight of the 10 were born in the Miyako island group and the remaining 2 on the main island of Okinawa. Since the subjects included 34 individuals who were living and/or born in the Miyako islands, the positive rate of anti-HDV in the islands was 23.5%. This study demonstrates the existence of an endemic area of HDV infection in Japan.     

The intrahepatic expression of the hepatitis B virus in chronic delta hepatitis

In order to evaluate the interference of hepatitis delta virus (HDV) in hepatitis B viral particle (HBsAg, HBcAg) expression in the liver of chronic HDV patients, 39 and 81 liver biopsies of HBsAg carriers seropositive for anti-HDV and anti-HDV negative controls, respectively, were studied. HBcAg was positive in 16.7% of the HBeAg-positive patients with HDAg in the liver and in 91,4% of controls. In contrast, in HBeAg- and anti-HDV negative patients the intrahepatic expression of HBcAg was detected in 32.6%. In anti-HDV negative patients the HBcAg liver expression correlated significantly with the HBeAg in serum (p < 0.00001). The distribution of HBcAg was exclusively cytoplasmatic in 30% of HDV-infected patients but mixed nuclear and cytoplasmic in 38.3% of the controls. The nuclear expression of HBcAg was decreased in chronic HDV infection. HBsAg was positive in 70.3% of patients who were anti-HDV positive and in 82.3% of controls. The membranous expression of HBsAg was detected less frequently in HDV-infected patients (p < 0.05) than in controls, while associated with HBeAg in serum of HBV carriers without HDV superinfection (p < 0.00001). The prevalence and the HBsAg cytoplasmic expression was not different for the chronic HDV infection or controls. Our results show: 1) decreased intrahepatic expression of HBcAg and membranous HBsAg in HBV carriers superinfected with HDV, suggesting decreased HBV replication in the liver of these patients. 2) the changing of HBcAg and HBsAg expression in the liver of HDV-infected patients, suggest not so much a decrease but rather a modulation in HBV replication.     

Determination of hepatitis delta virus (HDV)-RNA in asymptomatic cases of HDV infection

OBJECTIVES: To assess the frequency of hepatitis delta virus (HDV) viremia in asymptomatic cases of HDV infection and the clinical significance of the HDV viremia, we conducted a cross-sectional, community-based study. METHODS: Of 2207 examinees, 210 (9.5%) were found to be positive for hepatitis B surface antigen (HBsAg). Antibody to HDV was detected in 47 (22.4%) of the 210 examinees, and 43 of the 47 were further evaluated for serum HDV-RNA by polymerase chain reaction. RESULTS: Twenty-one (48.8%) of the 43 had detectable levels of HDV-RNA in serum, and 22 (51.2%) were negative for serum HDV-RNA. The majority (61.9%) of the HDV-RNA-positive HBsAg carriers had high levels of serum ALT. In contrast, the frequency of an abnormally high level of serum ALT was only 9.1% in the HBsAg carriers positive for HDV antibody but negative for HDV-RNA, and the frequency did not differ from that seen in the HBsAg-negative individuals. The semiquantified HDV-RNA levels did not correlate with the serum ALT levels. CONCLUSION: Seropositivity of HDV-RNA was strongly associated with liver cell damage, even in asymptomatic cases. The absence of a detectable level of serum HDV-RNA might be related to previous HDV infection.     

Viral hepatitis delta in the republic of Belarus

26,740 blood donors and persons of high risk groups with respect to HBV infection, residing in different regions of Belarus, were examined for the presence of HBsAg in 1983-1997. Of these, 1372 persons (5.1%) were found to have HBsAg, and out of 1081 HBsAg-positive persons anti-HDV antibodies (Ab) were detected in 96 persons (8.9%). In spite of a decrease in acute virus hepatitis B morbidity and in HBsAg carriership, the occurrence of anti-HBV Ab remained stable during the period of 16 years and was equal, on the average, about 4% among asymptomatic HBsAg carriers. Patients having tuberculosis, rheumatoid arthritis, diabetes mellitus, hematological diseases, chronic hepatitides and cirrhosis of the liver were an important reservoir of HBV and HDV infections for regions with the low level of the spread of HBV. A decrease in the detection rate of anti-HDV Ab in patients with cirrhosis of the liver from 47.6% to 15.4% was noted. In 1991-1997 a decrease in the detection rate of anti-HDV Ab in patients with chronic hepatic lesions in comparison with 1983-1990 was observed, and in the age group older than 50 years this decrease was from 33.3% to 8.3%. This difference was particularly pronounces in patients with cirrhosis of the liver: 53.9% and 7.7% respectively.     

Molecular biology of hepatitis D virus: research and potential for application

Superinfection by hepatitis D virus (HDV) leads to acute hepatitis and causes progression to liver cirrhosis in a significant proportion of hepatitis B surface antigen (HBsAg) carriers. Current regimens (interferon) to treat hepatitis D patients has only transient but no lasting effects. New approaches are, therefore, warranted. Recently, several laboratory studies have discovered interesting properties of HDV that may become targets for antiviral chemicals. Viral replication requires the small hepatitis delta antigen (s-HDAg). The s-HDAg is a nuclear phosphoprotein. There is evidence indicating that phosphorylation is important for HDV replication. A second step of replication requires HDV-RNA self-cleavage and self-ligation. Interestingly, one group of antibiotics, the aminoglycosides, exerts strong suppression effects on HDV ribozyme activities. In the following stage of viral assembly, two post-translational modifications, namely isoprenylation of large HDAg and glycosylation of HBsAg are involved. Agents capable of blocking the two modifications should reduce viral production. These four possible targets are reviewed. For prevention, effective vaccines are not yet available. Two novel approaches are discussed. The first demonstrates the immunogenicity of a nucleic acid vaccine in mice. The second approach assembled an empty HDV particle in yeast. Advances on such laboratory investigations may provide new methods for the control of hepatitis D in the future.     

Self-expanding metal oesophageal endoprostheses: which is best?

The main problem of children with HBeAg positive hepatitis B and associated hepatitis D is progression to liver cirrhosis with decompensation of liver function and need for liver replacement therapy within 15-20 years after infection. To determine whether interferon-alpha (IFN-alpha) therapy has a positive effect on HBV replication and inflammatory activity, we evaluated clinical and serological data of 8 children treated with IFN-alpha and 6 historic control patients without treatment. 4 of the nontreated patients seroconverted from HBeAg to anti-HBe between 7 to 17 years after initial diagnosis and showed decreased inflammatory activity in the liver. In the treatment group, the rate of seroconversion to anti-HBe (3 early, 2 late seroconverters) corresponded well to former trial results obtained in patients exclusively infected by HBV. Serum aminotransferase levels decreased or normalized in seroconverted children. In chronic HBV infection with associated hepatitis D (HDV) infection--compared to the spontaneous course of the disease--IFN-alpha therapy reduced inflammatory activity by earlier seroconversion to anti-HBe in responding patients. Moreover, viral replication and infectivity of hepatitis B was markedly reduced, but no effect on replication of HDV could be documented. Although long-term effects cannot be exactly estimated, at present IFN-alpha remains the only available treatment for HBeAg and anti-HDV positive children and seems to be of benefit for responding patients.     

Neonatal type 1 pneumococcal meningitis and maternal septicemia

Over a period of ten months, all the patients admitted for drug dependence were tested for HBsAg. The positive cases were tested for anti-HDV. The anti-HDV-positive patients were further tested for liver function tests (LFTs) and anti-HCV. A total of one thousand three hundred and twenty one patients were tested. Out of this, 1038 were intravenous drug users (IDUs) and 283 were non-IDUs. Eighty one patients were HBsAg positive (75 IDUs and six non-IDUs). Eleven patients were anti-HDV positive--all were IDUs. The overall prevalence of anti-HDV among HBsAg-positive patients was 13.6%. Among HBsAg-positive IDUs, it was 14.7% and it was 0.0% for HBsAg-positive non-IDUs. Nine (81.8%) of the eleven anti-HDV-positive patients were also positive for anti-HCV and eight (72.7%) had abnormal LFTs. In view of the association of hepatitis B, C and D viruses with chronic liver disease recommendations have been made to control the spread of these viruses and to prevent liver disease.     

Absenteeism in the workforce, Klang Valley, Malaysia--preliminary report

OBJECTIVE: We aimed to assess the seroprevalence of HBV, HCV and HDV virus markers in multi-transfused patients from Cluj-Napoca. MATERIAL AND METHODS: Stored serum samples of 105 multi-transfused patients (25 children, 19 adults and 61 chronically hemodialyzed patients) have been tested for HBsAg, anti-HBs, total anti-HBc, anti-HCV, total anti-HDV by automated ELISA (Sanofi Diagnostics Pasteur kits). RESULTS: HVC infection has been observed in 4/25 (16%) children, 14/19 (74%) multi-transfused adults and 48/61 (79%) haemodialysis patients. 8/25 (32%) children, 17/19 (89%) adults and 47/61 (77%) haemodialysis patients had HBV infection markers. Anti-HDV have not been found in HBV infected multi-transfused children and adults, respectively. Only 2/47 (4.25%) HBV infected haemodialysis patients had HDV infection markers. The prevalence of double infection (HCV and HBV) was high (4%, 84.2% and 67.2% in children, adults and haemodialysis patients). The prevalence of viral hepatitis markers correlated to the amount of transfused blood, and in haemodialysis patients also correlated to the duration on dialysis. CONCLUSIONS: In multi-transfused patients from Cluj area, the prevalence of viral hepatitis markers is high. The double infection (HCV and HBV) is frequent, especially in adults. The prevalence of HDV infection markers in HBV infected patients is low, in contrast with previously reported results.     

The immunological diagnosis of chronic viral hepatitis

Chronic viral diseases of the liver are associated with changes in immune reactions mediated by T and B lymphocytes and dependent in severity on etiological factor (virus of hepatitis B, delta, C, their combination), the disease stage (hepatitis, cirrhosis), the process activity, kind of immune correction. HBsAg, viral hepatitis B marker, was detected in 21.2% of 1400 cases with chronic active hepatitis and liver cirrhosis. 32% of HbsAg-seropositive patients had antibodies to delta-antigen. Antibodies to HBsAg, HCV were found in 27.7 and 14.9% of the above patients. Chronic viral diseases of the liver with persistence of HBV, HDV and HCV markers are characterized by a complex of immune disorders, including a moderate rise in peripheral blood of IgM, IgG, IgA, IgE, Ig kappa, lambda, immune complexes, cryoglobulins, autoantibodies to subcellular structures as well as changes in regulatory (suppressor, helper) and effector (lymphokine-producing) functions of T lymphocytes, inhibition of phagocytosing capacity. The above shifts in immune status, clinical and biochemical activity of the disease are more pronounced in chronic active hepatitis with HCV markers compared to BHV. Of maximal intensity they were in combined viral infection HBV+HDV or HBV+HCV.     

Recurrence of hepatitis D (delta) in liver transplants: histopathological aspects

BACKGROUND: The viral/pathological correlates of recurrent hepatitis delta virus (HDV) disease in orthotoptic liver transplants are reported. METHODS: We examined the histological features of recurrent HDV disease in nine patients with transplants for terminal HDV cirrhosis were examined; intrahepatic HDV and hepatitis B virus (HBV) antigens were detected by immunoperoxidase techniques. Sera were tested for the battery of HDV and HBV markers. RESULTS: In four patients, HDV reinfection was accompanied by the recurrence of an HBV infection with features of active viral replication. In the other five, HDV reinfection was accompanied by an atypical recurrence of HBV infection without evidence of active HBV replication (no expression of intrahepatic hepatitis B core antigen). In four of the latter patients, the atypical HBV pattern changed during the follow-up into a pattern of active viral replication accompanied by chronic necroinflammation detected during histology. CONCLUSION: The pattern of recurrent HBV infection can influence the pathological aspects of the relapses of HDV disease in liver grafts.     

Pneumococcal infections: penicillin resistance and therapeutic implications]

OBJECTIVE: We studied the prevalence of viral hepatitis B, C and D markers in chronic hepatopathies from Cluj. MATERIAL AND METHODS: Sera of 297 patients with chronic hepatopathies (236 adults and 61 children) have been tested for viral hepatitis markers: HBsAg, anti-HBc, anti-HBs, HBeAg, anti-HBe, anti-HDV, anti-HCV, by automated ELISA. RESULTS: HBV infection markers in 32% (adults) and 4.9% (children), and HDV infection markers in 11.8% (adults) and 26.3% (children). Double (HBV and HCV) and triple infection (HBV, HDV and HCV) were observed in 28.4% (adults), 4.9% (children), and 3.4% (adults), 0% (children), respectively. CONCLUSIONS: Hepatitis virus infection markers, especially HBV and HCV play an important role in the determinism of chronic hepatopathies from Cluj area, both in children and adults.     

The clinical importance of carpal instabilities following distal radial fractures

The association of viremia, elevated serum alanine aminotransferase (ALT) levels, and hepatocyte inflammatory activity in hepatocellular carcinoma (HCC) patients was studied. Serum samples from 114 HCC patients undergoing surgery were assayed for hepatitis B, C, and D viral nucleic acids by polymerase chain reaction (PCR) prior to surgery. Of these patients, 65 had HBV infection alone, 15 had HCV infection alone, 4 had HDV infection, 20 had HBV and HCV superinfection, 1 had triple viral infection, and 9 were negative for HBV and HCV infections. The prevalence of active viral replication was significantly higher in HCV than in HBV (92% versus 70%; P = 0.006) patients, and significantly higher mean serum ALT levels were also noted in the HCV group than in the HBV group (P = 0.02). The incidence of marked ALT elevation (>200 U/l) was highest in the HCV (27%) and the HDV (25%) groups. Patients in the HCV group were 10 years older than those in the HBV group. Viral superinfection did not accelerate the development of HCC. Viral replication persisted in a significant portion of HCC patients and a higher prevalence of hepatic inflammation was noted in patients with HCV- and, possibly, HDV-related HCC.     

Human fascioliasis: comparison of a fasciolicidal effect of bithionol and praziquantel

BACKGROUND: The frequency of gliadin antibody (GA) positivity has been found to be increased among patients with chronic liver disease, as has that of coeliac disease (CD). CD has also been found to be increased among patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). METHODS: To investigate these relationships further, a micro-enzyme-linked immunosorbent assay and immunofluorescence tests for GAs and endomysial antibodies (EMAs) were performed in large subgroups of patients representing various chronic liver diseases and in healthy blood donors. RESULTS: As compared with blood donors (among whom it was 5%) the frequency of IgA GA positivity was higher in all patient subgroups: alcoholic liver disease, 20% (22 of 110, P < 0.001); PBC, 16% (16 of 101, P < 0.001); PSC, 24% (19 of 80, P < 0.001); chronic hepatitis, 19% (13 of 70, P < 0.001); and hepatitis C virus infection, 11% (11 of 104, P < 0.01). Two patients with autoimmune chronic hepatitis were EMA-positive, and in both cases the presence of CD was verified by small-bowel biopsy. CONCLUSIONS: IgA GA positivity generally occurs at increased frequency among patients with chronic liver disease and may represent non-specific immune activation. In liver disease GA testing is not useful in screening for CD, whereas the EMA test seems to be highly specific. CD is more prevalent than expected among patients with autoimmune chronic hepatitis but not among those with PBC or PSC.     

GB virus-C/hepatitis G virus infection in an area endemic for viral hepatitis, chronic liver disease, and liver cancer

BACKGROUND & AIMS: GB virus-C/hepatitis G virus (GBV-C/HGV) is a newly identified flavivirus, and little is known about its clinical significance. GBV-C/HGV was investigated in different populations, and its coinfection was investigated in patients with liver disease in Taiwan where hepatitis B and C are endemic. METHODS: Viral RNA was studied in 70 high-risk individuals, 20 patients with chronic non-B, non-C hepatitis, 13 with non-A-E fulminant hepatitis, 100 with asymptomatic hepatitis B surface antigen carriage, 120 with hepatitis B surface antigen-positive chronic liver disease and hepatocellular carcinoma, 100 patients with chronic hepatitis C, and 100 healthy adults. RESULTS: GBV-C/HGV infection was more frequent in high-risk groups (15%-30%) and hepatitis C virus carriers (10%) than in healthy adults (1%) and hepatitis B virus carriers (3.2%). Eighty-three percent of those infected had undergone blood transfusions previously. The prevalence in hepatitis B virus carriers increased with the severity of liver disease, being 1% in asymptomatic carriers and 10% in hepatocellular carcinoma. In chronic hepatitis C, clinical and virological data were comparable between those with and without coinfection. CONCLUSIONS: In Taiwan, GBV-C/HGV infection is common in high-risk groups, and its coinfection seems to not aggravate the course of chronic hepatitis B or C.     

An evaluation of the degree of the morphological activity and the stage of the process in patients with chronic liver diseases caused by coinfection with the hepatitis B, C and/or D viruses

In order to determine the differences in histological grade of activity and the stage of fibrosis in patients with chronic liver diseases due to multiple hepatitis virus infection and single infection of HBV and HCV we assessed the 68 liver biopsies samples according to Knodell and Scheuer scoring systems. Retrospectively, 216 liver biopsies reports from consecutive patients with chronic viral hepatitis were analysed. Histological activity index (HAI) in HBV/HCV coinfection was higher than in a single HCV infection; it did not differ in groups of HBV/HBC and HBV. The difference was due to the interface hepatitis; lobular activity and portal inflammation were the same. In HDV superinfection HAI was high due to both portal-periportal and lobular hepatitis. HAI depended mainly upon the presence of HBV replication; in patients with chronic hepatitis C with HBV-DNA HAI was also higher than in single HCV group. No difference in HAI between triple and dual hepatitis virus infection was found. In patients with HBV/HCV coinfection and especially with HDV superinfection the advanced stages occurred more than often than in patients with single infections.     

Fine needle aspirative biopsy of the liver in HBsAG-positive patients with end-stage renal failure

HBsAg-positive patients with end-stage renal failure have a high prevalence of asymptomatic chronic hepatitis. In order to determine the usefulness of hepatic cytology in the diagnosis of liver disease, the findings of hepatic needle core biopsy (NCB) and fine needle aspirative biopsy (FNAB) were compared in 15 HBsAg-positive uremic patients. The patients, aged 42 +/- 12 years, 14 males, were on hemodialysis for periods ranging from 13 to 105 months. The NCB was processed by standard histologic and immunohistochemical techniques and FNAB by the conventional technique, using the total corrected increment score (TCI). Plasma samples were collected for evaluation of hepatic function and for viral serologic tests. In 15 patients a diagnosis was made by NCB: normal, 7 cases; chronic persistent hepatitis, 4 cases; and chronic active hepatitis, 4 cases. When the patients were allocated into two groups according to the severity of the liver histologic findings [group I--minor changes (normal+chronic persistent hepatitis), 11 patients; group II--major changes (chronic active hepatitis), 4 patients], statistically higher values were found in the major changes group for alanine aminotransferase (49 +/- 33 vs. 24 +/- 11, p = 0.04), gamma-glutamyl transpeptidase [148 +/- 53 vs. 38 +/- 28, p < (minor) 0.02] and TCI (3.7 +/- 1.2 vs. 2.5 +/- 0.8, p = 0.04). In conclusion, liver FNAB can be useful as a screening procedure for the identification of liver histologic changes (minor or major) in uremic HBsAG-positive patients.     

Detection of replicative form of HCV RNA in peripheral blood leukocytes and its clinical significance

Nested RT-PCR, done by using degenerated primer pair, was used to detect hepatitis C virus RNA (HCV RNA) in serum, plasma, liver and peripheral blood leukocytes (PBLC) of 30 patients with acute and chronic posttransfusion hepatitis C and 7 asymptomatic anti-HCV positive subjects. The results showed that the percentage of positive HCV RNA in PBLC, including both the plus and minus strands, in patients with chronic hepatitis C was significantly higher than that in acute hepatitis C and asymptomatic anti-HCV positive subjects (P < 0.05-0.001). All the 7 asymptomatic anti-HCV positive subjects did not have detectable minus strand of HCV RNA in their PBLC, serum or plasma. In 17 patients who had liver histologic examination, the positive rate of both strands of HCV RNA in PBLC of acute hepatitis (AH) was lower than that of chronic active hepatitis (CAH) (P < 0.05). Both strands of HCV RNA were detected in the liver of one AH and 6 CAH patients. The present data confirmed that PBLC of patients with hepatitis C were indeed infected by HCV. The longer the infection time, the more the chance of PBLC being infected by HCV. Patients with active liver disease (CAH) had usually higher positive rate of minus strands of HCV RNA in PBLC. In the serum and plasma of all the 37 cases, minus strand of HCV RNA was not detected and the positive rate of the plus strand of HCV RNA in their serum and plasma was similar. Futhermore, the positive rate of both plus and minus strands of HCV RNA in PBLC of 30 patients with chronic hepatitis C was also similar. It is suggested that HCV not only may infect PBLC, but also replicate in PBLC and that the occurrence of minus strand of HCV RNA is associated with activity of liver disease.     

Interrelationship between beta-amyloid deposition and complement-activated oligodendroglia

PURPOSE: To assess the reliability of the size-overestimation ratio obtained from spiral CT arterial portography (CTAP) and spiral equilibrium-phase CT (EPCT) in distinguishing malignant focal hepatic lesions from benign ones. METHODS: The CTAP images and EPCT images obtained five minutes after CTAP in 39 patients with focal hepatic lesions were retrospectively analyzed. Fifty-eight lesions (hepatocellular carcinoma [HCC], 33; metastasis, 10; liver cyst, 10; cavernous hemangioma, 2; adenomatous hyperplasia [AH], 2; focal nodular hyperplasia [FNH], 1) had their sizes measured on CTAP and EPCT images using the calipers on the CT console. RESULTS: The size-overestimation ratios (CTAP/EPCT) were 1.24+/-0.15 in HCC, 1.28+/-0.26 in metastasis, 1.02+/-0.23 in liver cyst, 0.98+/-0.34 in cavernous hemangioma, 0.94+/-0.39 in AH, and 1.00 in FNH. Mean size-overestimation ratios for benign- and malignant-lesion groups were 1.00+/-0.37 and 1.25+/-0.18, respectively (p < 0.0001). When a cutoff level was set at 1.05, sensitivity and specificity for malignancy were 91% and 93%, respectively. CONCLUSIONS: In comparison with EPCT, CTAP significantly overestimates the size of malignant hepatic tumors. This phenomenon may be an indicator of hepatic malignancy.     

Rapamycin: distribution, pharmacokinetics and therapeutic range investigations: an update

The prevalence of hepatitis C virus (HCV) infection increases with advancing age, but the disease has been poorly studied in the elderly. A population-based study was therefore carried out to investigate the prevalence of HCV infection and the severity of HCV-related chronic liver disease in the elderly. One thousand and sixty-three people (> or = 60 years of age) were screened for antibodies to HCV (anti-HCV) and for possible abnormalities of common liver function tests. Positive subjects and sex and age-matched anti-HCV-negative controls were recalled 12 months later for measurements of liver enzymes, confirmatory testing of anti-HCV, HCV RNA analysis and HCV genotyping. All subjects answered a specific questionnaire concerning medical history and possible risk factors. Forty-four subjects were positive for anit-HCV, the prevalence being 4.1%. Thirty-five positive subjects and 35 controls were investigated further. Risk factors for acquiring HCV were found to be: blood transfusion, surgical intervention and the use of non-disposable syringes. Abnormal alanine aminotransferase levels were found in 13 patients (37.1%). HCV RNA genotyping showed type 1b in three (15.8%), type 2a in 13 (68.4%) and not classified in three (15.8%) patients. There was no relationship between abnormalities of serum aminotransferase, the rate of HCV RNA positivity and HCV genotypes. Ultrasound abnormalities were present in 13 (37.1%) patients. In this elderly population the relatively high prevalence of HCV infection was thought to be caused by previous parenteral exposure. The low incidence of liver disease could be related to the prevalence of HCV genotype 2a in the majority of these patients, and hints at the possibility of an HCV carrier state in elderly individuals.     

Modeling perceived relationships between melody, harmony, and key

A small open reading frame (ORF) was found in the hepatitis delta virus (HDV) antigenomic RNA encoding a short peptide that shares structural similarity with a region of the hepatitis B virus terminal protein. Analysis of all published HDV genome sequences indicates a high degree of conservation for the small ORF. This ORF is located at the 3'-terminal region of the gene encoding the hepatitis delta antigen (HDAg). We speculated that a peptide encoded by this ORF can be represented as the C-terminal domain of a new protein called HDAg'. This protein contains almost the entire sequence represented in the small form of HDAg and a peptide as an additional 'extension' sequence at the C-terminus. Two long synthetic peptides representing the two different types of peptides encoded by the small ORF were synthesized. These peptides were used for the development of an immunoassay for the detection of antibody to the HDAg' specific domain in sera of patients with HDV infection. Among 162 serum samples analyzed, 13 were found to be positive for an antibody reactive with these synthetic peptides. These antibodies were identified in patients with HDV infections and were not found in patients infected with hepatitis B virus, hepatitis C virus, or non-A,non-B,non-C virus. Thus, these data support the identification and existence of a new antigen encoded by the antigenomic RNA of the HDV.