A prospective clinical trial of D-penicillamine in the treatment of primary biliary cirrhosis.

We conducted a prospective clinical trial to assess the relative efficacy and safety of high- vs. low-dose D-penicillamine in patients with primary biliary cirrhosis. Following clinical tests and liver biopsy diagnostic of primary biliary cirrhosis, 56 patients were randomized to receive either 250 or 750 mg D-penicillamine daily.

Detection of two forms of HBeAg (free-and IgG-bound HBeAg) in patients with HBe antigenemia using staphylococcus bearing protein A.

Protein A-bearing Staphylococcus aureus organisms (STA) were used to separate free HBeAg from IgG-bound HBeAg. Free HBeAg was detected in the supernate while IgG-bound HBeAg could be liberated from the pellets using MgCl2 or a glycine buffer. HBeAg was determined by radioimmunoassay and the results expressed as patient's cpm/normal control's cpm ratio (S/N ratio).

Randomized controlled trial of quinacrine for the treatment of HBsAg-positive chronic hepatitis.

Several drugs which react with DNA decrease hepatitis B viral (HBV) DNA polymerase activity in vitro. Because such an alteration of viral replication, if produced in patients with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis, may lead to elimination of viral infection, we conducted a controlled trial of the use of the intercalating agent, quinacrine hydrochloride, in treatment of HBsAg-positive chronic hepatitis. No patient converted from HBsAg positive to negative during the trial and no consistent effect on HBV DNA polymerase activity was noted.

Circulating complement fixing immune complexes in chronic hepatitis. Use of anti-C3 enzyme immunoassay to define antibody class and nature of antigen.

An anti-C3 enzyme immunoassay (anti-C3 EIA) was used to identify the antigen and antibody of immune complexes (IC). HBsAg, liver cell membrane antigens (LSP and LP-2), IgA, IgG and IgM were determined in IC of 258 patients with chronic active hepatitis (CAH) and 31 patients with chronic persistent hepatitis (CPH). IC that contained an antibody of either IgG, IgM or IgA class were detected in all types of CAH and CPH investigated.

In vitro synthesis of IgG and IgM in patients with HBsAg-positive and HBsAg-negative chronic active hepatitis.

Spontaneous and PWM-driven IgG and IgM synthesis was investigated in the PBMC of 15 patients with HBsAg-negative CAH and six HBsAg-positive patients with CAH. PBMC from patients with HBsAg-positive CAH show an impaired IgG synthesis upon stimulation with PWM but an IgM increase similar to that of control subjects. In contrast, PBMC from HBsAg-negative patients with CAH show a trend to spontaneous increased synthesis of IgG and a decrease or lack of IgG and IgM synthesis upon PWM stimulation.

Geographic differences in HBV related, autoimmune, and cryptogenic chronic active hepatitis.

To clarify the importance of ethnic and geographic factors in chronic active hepatitis (CAH), HBV markers and autoantibodies (AMA, ANA, SMA), have been compared in 158 patients with biopsy-proven CAH from New York City and in 92 patients with CAH from Milan. HBsAg-positive CAH was more frequently observed in Milan (49%) than in New York City (27%). However, among HBsAg-positive patients, HBcAg, HBeAg, and epidemiologic risk factors for acquisition of HBV infection were more frequently found in New York than in Italy.

Radioimmunoassay for hepatitis B core antigen.

Serum hepatitis B core antigen (HBcAg) is an important marker of hepatitis B virus replication. We describe an easy, sensitive radioimmunoassay for determination of HBcAg in detergent-treated serum pellets containing Dane particles. Components of a commercial kits for anti-core determination are used, and HBcAG is measured by competitive inhibition of binding of 125I-labeled antibodies to HBcAg with HBcAg-coated beads.

Cell-mediated immunity to HBcAg and HBsAg in patients with chronic hepatitis.

The leukocyte adherence technique (LAT) has been utilized to assess cell-mediated immunity (CMI) to HBcAg and HBsAg in patients with chronic (CH) and acute viral (AVH) hepatitis. All patients with AVH type B and 91.6% of patients with HBV-related CH displayed reactivity to both HBcAg and HBsAg, whereas healthy controls and patients with liver disease not related to HBV failed to show reactivity to these antigens.

A radioisotopic leukocyte adherence test.

A modification of the leukocyte adherence inhibition method is described which utilizes 51Cr-labeled blood mononuclear cells placed in microwells. The test is reproducible, objective, employs approximately 2,000 cells per well, and allows multiple replicates of several antigens. With the two antigens tested, SK-SD and PPD, both increases and decreases of leukocyte adherence are observed.

Dane particles-associated hepatitis B core antigen in patients with HBsAg-positive chronic hepatitis.

Dane particles-associated hepatitis B core antigen (HBcAg) was determined by radioimmunoassay in 61 patients with hepatitis B surface antigen (HGsAg)-positive chronic hepatitis. HBc antigenemia was observed in 61% of patients, especially in those with epidemiological risk factors. Patients with chronic active hepatitis as well as those with chronic persistent hepatitis may have HBc antigenemia.

Immune response to hepatitis B virus in children with papular acrodermatitis.

Papular acrodermatitis of childhood (PAC) is characterized by papular eruption of skin, lymphadenopathy, and acute hepatitis B surface antigen (HBsAg)-positive anicteric hepatitis. To study the course of hepatitis B virus infection we followed 16 patients with PAC, 2 to 7 years of age, for periods ranging from 6 to 46 months. All patients tested developed hepatitis B surface antigenemia subtype ay, and produced antibody to hepatitis B core antigen with the highest incidence after 3 to 5 months.

T and B lymphocytes in patients with chronic active hepatitis (CAH).

Absolute numbers of T and B lymphocytes as well as active E rosette-forming cells were measured in twenty-seven patients with chronic active hepatitis (CAH), and in thirty control patients. In patients with CAH without cirrhosis, active E rosette-forming cells (a subpopulation of T lymphocytes considered to be actively involved in cell-mediated immune reactions) as well as lymphocytes with surface markers for IgA, IgM and IgG were increased. In patients with CAH and cirrhosis, total T lymphocytes were decreased.

Antibodies to hepatitis B core antigen in hepatitis B surface antigen-positive and -negative chronic hepatitis.

Antibody to hepatitis B core antigen (anti-HBc) is a sensitive indicator of hepatitis B virus (HBV) infection. However, anti-HBc has been found in only a few patients with chronic hepatitis. Therefore, we tested for anti-HBc in 124 sera from 67 patients with histologically proven chronic hepatitis by the indirect fluorescent antibody technique.

Extrahepatic malignancy in chronic liver disease: report of six cases.

Six patients are described with chronic liver disease, 3 with primary biliary cirrhosis and 3 with chronic active hepatitis, all of whom developed malignant disease in organs other than the liver. Two malignancies were mixed histiocytic-lymphocytic lymphomas. All patients had received corticosteroid or azathioprine therapy.

Immune complexes in hepatocytic nuclei of HB ag-positive chronic hepatitis.

To localize immune complexes in viral hepatitis Type B and to assess their pathogenic role, we examined by the direct fluorescent-antibody technic 21 liver specimens with hepatitis B core antigen (HBc Ag) in hepatocytic nuclei from 10 patients with HBs Ag-seropositive acute viral hepatitis and from 11 patients with HBs Ag-seropositive chronic active hepatitis. IgG with in vitro fixation of complement was demonstrated in HBc Ag-containing hepatocytic nuclei of all patients with chronic active, but not in those with acute viral hepatitis. All patients except for one had antibody to HBc Ag in the serum as determined by indirect immunofluorescence.

Hepatitis B surface antigen and antibody. A prospective study in asymptomatic drug abusers.

The course of reactivity of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in 238 asymptomatic heroin addicts entering methadone maintenance was followed up for periods of one to four years. On initial determination, HBsAg was seen in 39.1%, anti-HBs in 10.

Cell-mediated immune reactivity to hepatitis B surface antigen in liver diseases.

The cellular immune reactivity to hepatitis B surface antigen (HBsAg) was studied in patients with liver diseases using a purified preparation of HBsAg and the leukocyte-migration agarose test. Inhibition of leukocyte migration by HBsAg was found in all 9 patients in the acute phase of viral hepatitis but not during convalescence. HBsAg inhibited migration of leukocytes in only 1 of 15 patients with chronic persistent hepatitis, in none of 16 with chronic periportal hepatitis, and in 2 of 21 with nonhepatic liver diseases.

Incidence and nature of cytoplasmic hepatitis B antigen in hepatocytes.

Hepatitis B antigen (HB Ag) in the hepatocytic cytoplasm is detected by immunofluorescence after reaction with fluoresceinated antiserum to HB Ag or by electron microscopy as numerous 20- to 30-nm. tubular and circular structures in dilated cisternae of excess endoplasmic reticulum. On light microscopy, these hepatocytes can be recognized because their cytoplasm has a ground-glass appearance and stains with Gomori's aldehyde fuchsin.