Antigen-positive Chronic Hepatitis Research Articles

Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis: A prospective study

A prospective surveillance of hepatocellular carcinoma (HCC) using serum α-fetoprotein and high-resolution, linear-array, real-time ultrasonography was carried out in 432 patients with clinicopathologically proven chronic type B hepatitis. During a follow-up period of 6–85 mo (median 23, mean 26.9 ± 16.8 mo), asymptomatic HCC was identified in 8 patients, with a calculated annual incidence of 826/100,000, and 2768/100,000 for patients over age 35 yr. The relative risk of developing HCC in hepatitis B surface antigen-positive chronic hepatitis patients was 2 when compared to those that were hepatitis B surface antigen-negative, and was 5 when compared in patients over age 35 yr. Hepatocellular carcinomas detected by these methods were in a relatively early stage as most tumors were small, only 50% were associated with cirrhosis, 37.5% were positive for hepatitis B e antibody, and most were still resectable. We, therefore, recommend a combination of α-fetoprotein and ultrasonography surveillance in patients with chronic hepatitis in order to improve the chance of early HCC detection as well as the chance for successful resection. In addition, the low incidence of cirrhosis and hepatitis B e antibody in these patients with “early” HCCs and the occurrence of hepatitis B e antigen/hepatitis B e antibody seroconversion after HCC had developed suggest that the development of HCC and progression from hepatitis to cirrhosis were two independent (though related) sequelae of chronic hepatitis B virus infection.

Clinical, serologic, and immunologic effects of human leukocyte interferon in HBsAg-positive primary hepatocellular carcinoma.

Five patients with hepatitis B surface antigen (HBsAg) positive chronic hepatitis and histologically confirmed primary hepatocellular carcinoma (PHC) were treated with 3 X 10(6) units/day of partially purified human leukocyte interferon intramuscularly for 2 consecutive months. During interferon therapy, one patient had stable disease, while the remaining four patients had progressive disease. Following interferon therapy no changes were noted in the hepatitis B viral markers or in serum alphafetoprotein levels. Data on the effects of human leukocyte interferon on lymphocyte subpopulations and on the cytotoxic activity of peripheral blood mononuclear cells against a hepatitis B surface antigen expressing primary hepatocellular carcinoma cell line are presented.

Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B: A controlled study

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4–8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.

Recombinant Leukocyte A Interferon Treatment in Patients With Chronic Hepatitis B Virus Infection: Pharmacokinetics, Tolerance, and Biologic Effects

Large doses of recombinant leukocyte A interferon were administered to 20 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis B to study the maximum tolerated dose, its pharmacokinetics, and its antiviral activity. The first group of 5 patients received a constant dose of 36 X 10(6) U/day for 28 consecutive days. When it was well tolerated, the second, third, and fourth groups (5 patients each) received 50, 72, and 100 X 10(6) U/day, respectively. All 20 patients completed the 28-day treatment. Hourly and daily profile of serum interferon level showed a dose-dependent effect with an increasing dosage, and cumulative effects during the treatment. The mean peak serum interferon concentration ranged from 93 U/ml on day 1 in the first group to 1271 U/ml on day 28 in the fourth group. Inhibition of serum deoxyribonucleic acid polymerase activity and hepatitis B virus-deoxyribonucleic acid during the treatment was compared between the groups with low doses (36 and 50 X 10(6) U) and high doses (72 and 100 X 10(6) U). Low doses of interferon suppressed deoxyribonucleic acid polymerase activity to the same extent as did the high doses. Prednisolone withdrawal was combined with interferon in 5 patients. Three patients treated with such combination became seronegative for hepatitis B e antigen during the treatment, whereas all 15 with interferon alone remained seropositive. These results suggest that a maximum antiviral effect of recombinant leukocyte A interferon is below the maximum tolerated doses.

Long-term delta superinfection in hepatitis B surface antigen carriers and its relationship to the course of chronic hepatitis

To assess the prevalence and clinical significance of δ-infection in chronic hepatitis B surface antigen carriers, we examined 326 liver biopsies from 192 retrospectively selected carriers by immunofluorescence. Delta antigen was detected in 102 specimens from 50 carriers (26.2%) with peak prevalence in patients with active cirrhosis (51.5%) and generally in close association with progressive liver disease (94%). The antigen was located in the nuclei of 2%–50% of the hepatocytes, without any disease-specific pattern of fluorescence. Patients with intrahepatic delta-antigen, however, had more severe liver disease than those without it. Histologic follow-up of 101 cases showed that the rates of worsening of the liver disease were similar in delta-antigen-positive and in delta-antigen-negative patients. It is concluded that delta-superinfection does play a role in worsening the histologic picture of hepatitis B surface antigen-positive chronic active hepatitis, possibly by liver injury induced acutely at the moment of infection.

Virus-Associated Receptors for Polymerized Human Serum Albumin in Acute and in Chronic Hepatitis B Virus Infection

The receptor for polymerized human albumin, recently identified on the hepatitis B virus, was studied by hemagglutination in 89 patients with acute and chronic hepatitis B virus infection. The receptor, which was differentiated from antialbumin antibodies by immunofluorescence and hemagglutination inhibition, was detected mainly in patients with active virus replication, independently of hepatitis B surface antigen titer. Thirteen of 20 uncomplicated acute hepatitis B cases were positive at clinical onset (mean log2 titer +/- SD: 4.20 +/- 2.46) but became negative during the acute phase, while 5 patients who progressed to chronic hepatitis had significantly higher receptor titers at onset (7.0 +/- 0.0, p less than 0.01) and remained positive afterwards. In chronic hepatitis B virus infection, the receptor was detected in 17 of 30 patients with chronic active hepatitis, in 5 of 12 with chronic persistent hepatitis, and in 2 of 16 healthy carriers. Among hepatitis B e antigen positive cases a wide range in receptor levels was observed, and in longitudinal studies most patients with low initial titers seroconverted to hepatitis B e antibody while patients with higher titers remained persistently hepatitis B e antigen positive. These results indicate that the virus receptor for polyalbumin may represent a useful marker in hepatitis B e antigen positive acute and chronic hepatitis B.

Therapeutic effect of a low dosage of human leukocyte interferon on chronic hepatitis B virus infection.

A low dosage of human leukocyte interferon was intramuscularly given to 47 patients with hepatitis B surface antigen (HBsAg) positive chronic active hepatitis once a week for 4 consecutive weeks (10 X 10(5), 5 X 10(5), 2 X 10(5) and 1 X 10(5) U). After treatment, a reduction of serum HBsAg was observed in 26 patients; 3 of them showed no serum HBsAg and 1 of the 3 appeared to produce antibody to HBsAg. 31 of 34 patients investigated showed a significant decrease in Dane particle-associated DNA-polymerase activity (p less than 0.001). Among 17 patients positive for hepatitis B e antigen (HBeAg), 10 of them seroconverted to anti-HBe. Serum transaminase levels also significantly improved in 34 of 38 patients (p less than 0.001). Our findings indicate that a low dosage of human leukocyte interferon such as 18 X 10(5) U, administered in progressively decreasing doses, may be effective in the treatment of chronic hepatitis B virus infection.

Electron and Immunoelectron Microscopic Study of Dane Particle Formation in Chronic Hepatitis B Virus Infection

The site of Dane particle formation in hepatocytes was studied by routine electron and immunoelectron microscopy of liver biopsy specimens from 10 patients with hepatitis B e antigen-positive chronic active hepatitis. With routine electron microscopy, core particles were abundant in cytosol, often adjacent to the cell membrane, and occasionally in the microvilli. Figures suggestive of budding of endoplasmic reticulum with a core particle into the cisternae of endoplasmic reticulum were observed frequently. There were also figures suggestive of direct budding with a core particle from the surface of the cell. With the immunoelectron microscopy, the core particles were found to be positive for hepatitis B core antigen and the endoplasmic reticulum and the plasma membrane were positive for hepatitis B surface antigen. These findings suggest that the most plausible mode of formation of the Dane particle is by budding of hepatitis B surface antigen-positive endoplasmic reticulum membrane into the cisternae. In addition, formation of the Dane particle may also take place at the surface of the hepatocyte by a similar mechanism.

The diagnostic value of the ratio of serum gamma-glutamyl transpeptidase to alkaline phosphatase in alcoholic liver disease.

A prospective study of the initial liver laboratory tests was carried out in the following patients: 55 patients with alcoholic liver disease, 53 with cholangitis, 41 with hepatocellular carcinoma, 65 with acute viral hepatitis, and 49 with hepatitis-B surface antigen-positive chronic active hepatitis. There was considerable overlap in the levels of the serum gamma-glutamyl transpeptidase (GT) and alkaline phosphatase (AP) among the five groups. However, the ratio of GT to AP was significantly higher in the group with alcoholic liver disease than in any of the other four groups. When the ratio was higher than 1.4, the diagnostic efficiency for distinguishing the alcohol group from the other four groups was 78% (the normal upper limit for GT and AP being 35 and 115 U/1, respectively). A possible explanation for this higher ratio in alcoholic liver disease is suggested. We conclude that when the GT and AP is greater than 1.4, it is of greater diagnostic value than either variable alone in differentiating alcoholic from other liver diseases.

Failure to detect naturally occurring serum inhibitors of hepatitis B virus deoxyribonucleic acid polymerase.

Sera of patients with past or ongoing hepatitis -B virus infection were tested for the presence of inhibitors of hepatitis -B virus-specific deoxyribonucleic acid (DNA) polymerase activity. None of the sera tested, which included those from anti-hepatitis B surface- and anti-hepatitis B core antigen-positive hemophiliacs, anti-hepatitis Bc antigen-positive hepatitis B surface antigen carriers, patients with hepatitis B surface antigen-positive chronic active hepatitis, hepatitis B surface antigen-positive hemodialysis patients, tumor patients with minimal hepatitis, patients with acute type B, type A, and type non-A, non-B hepatitis and individuals with autoimmune phenomena, contained inhibitors of DNA polymerase activity. This implies that the DNA polymerase test is not affected when utilized to quantitate DNA-containing Dane particles. In addition, there is no evidence that inhibitors of DNA polymerase activity play some pathogenic role in the course of hepatitis B virus infection.

Electron microscopy of hepatitis B virus components in chronic active liver disease.

Eighteen liver biopsy specimens from patients with hepatitis B surface antigen (HBsAg) positive chronic aggressive hepatitis were studied by electron microscopy. All cases were selected on the basis of positive liver cell membrane fluorescence for HBsAg on immunohistochemical investigation. Striking changes in the morphology of the liver cell membrane were observed in nearly all cases. Furthermore, a dual aspect of hepatitis B core antigen (HBcAg) is described. HBcAg particles may occur as either 'naked' or 'cloudy' particles surrounded by semi electron dense material. The nature of the 'cloud' remains to be identified.

Reversibility of hepatitis B virus-induced glomerulonephritis and chronic active hepatitis after spontaneous clearance of serum hepatitis B surface antigen

A patient presenting with nephrotic syndrome was found to have hepatitis B surface antigen-positive chronic active hepatitis and membranoproliferative glomerulonephritis. Glomeruli stained positive for hepatitis B surface antigen, IgG, and C1q. After spontaneous clearance of hepatitis B surface antigen both the glomerulonephritis and the chronic active hepatitis improved. The natural history, pathogenesis, and treatment of this disease complex are discussed.

Electron microscope study of a case of Australia antigen-positive chronic hepatitis.

The laboratory findings in a case of Australia antigen (Au-Ag) positive chronic hepatitis in a 4-year-old boy are given. Studies by the electron microscope technique of thin sectioning revealed the presence of 200A particles in the nuclei of hepatocytes. These particles are identical to those described previously in occasional specimens of Au-Ag-positive liver tissue. However, the pattern found here differs from previous descriptions inasmuch as no heavily infected nuclei could be found but almost all nuclei could be shown to contain extremely small numbers of these particles. The significance of this finding is discussed and the danger that it would be easy to obtain false negatives in similar tissue pointed out.

Dane particles in the sera of patients with chronic aggressive hepatitis.

Dane particles were observed electron microscopically in sera of all 10 patients with Australia (Au) antigen-positive chronic aggressive hepatitis. Massive Dane particles were demonstrated in sera of a patient at the early phase of the elevation of serum glutamic pyruvic transaminase. The inner body of a Dane particle was shown as a typical icosahedral symmetry by rotation technique.