ElizabethA. Fagan

SERUM AMYLOID-A PROTEIN CONCENTRATION IN INFLAMMATORY DISEASES AND ITS RELATIONSHIP TO THE INCIDENCE OF REACTIVE SYSTEMIC AMYLOIDOSIS

Serum amyloid-A protein (SAA) is the putative precursor of amyloid-A (AA) protein which forms the fibrils in reactive systemic or secondary amyloidosis. By means of a novel immunoradiometric assay, the concentration of SAA was found to be greatly elevated in patients with rheumatoid arthritis and juvenile chronic arthritis and correlated with activity of their primary disease. However, in patients with systemic lupus erythematosus SAA levels were only modestly raised, even in those with severe active disease, unless significant intercurrent microbial infection was also present. In Crohns disease SAA levels showed a pattern similar to that seen in rheumatoid arthritis, whereas in ulcerative colitis it resembled that of systemic lupus erythematosus. The level of SAA response in these different disorders corresponds with the incidence of reactive systemic amyloidosis in them. These observations support the view that major increases in SAA levels are a necessary condition for the deposition of this form of amyloid and suggest that prospective monitoring of the SAA concentration in predisposing diseases may help to identify those individuals who are most at risk for amyloidosis.

FULMINANT HEPATITIS B IN SUCCESSIVE FEMALE SEXUAL PARTNERS OF TWO ANTI-HBe-POSITIVE MALES

In two separate families, consecutive, unrelated female sexual partners of a symptom-free, male, HBsAg-positive carrier died of fulminant hepatitis B. Although one man was HBeAg positive on the first occasion, both men were considered of low infectivity, being anti-HBe positive, negative for serum DNA polymerase activity, and negative for serum hepatitis B virus (HBV) DNA when their second partners presented with fulminant hepatitis B. By means of molecular hybridisation techniques, both men were found to have HBV DNA (3.2 kb) in seminal fluid, sputum, saliva, peripheral blood leucocytes, and liver.

A controlled trial of 6 months thrice weekly lymphoblastoid interferon versus no therapy in chronic hepatitis B virus infection: A preliminary analysis of the first 32 patients

A controlled trial of lymphoblastoid interferon versus no therapy in patients positive for HBsAg, HBeAg and DNA polymerase activity with separate randomisation for sexual preference and histology is underway. Thirty two patients have been followed for a minimum period of 6 months of whom 15 have been randomised to receive interferon thrice weekly for 6 months after a 5-day induction phase. Five treated patients developed an hepatitis-like illness during the 3rd month of therapy concurrent with an abrupt and complete loss of DNA polymerase activity from serum. In 3 this was permanent and anti-HBe subsequently developed; 2 of these have also lost HBsAg. In the other 2 patients inhibition of viral replication was transient. In 5 further treated patients DNA polymerase activity was completely inhibited throughout treatment only to return as soon as interferon was withdrawn. In this group serum aminotransferase became normal during treatment. In the remaining 5 treated patients, inhibition of DNA polymerase activity was never complete and serum aminotransferases were unaffected. All the control patients remain seropositive for HBsAg, HBeAg and DNA polymerase activity. The low seroconversion rate in treated patients and the absence of seroconversion in the control group are probably a reflection of the exclusion of patients with marked elevation of serum aminotransferases. The occurrence of an hepatitis-like illness in the 3rd month of therapy in a third of the patients and the loss of HBsAg in 2 of 3 who eventually seroconverted are likely to be a consequence of therapy rather than spontaneous events.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled trial of acyclovir in stable chronic HBsAg, HBeAg-positive carriers

Histological remission is recognised to follow loss of viral replication in chronic hepatitis B virus infection. The aim of antiviral therapies has been to accelerate seroconversion from HBeAg to anti-HBe, but so far none has been shown to be of significant advantage in adequate, controlled trials and toxicity has been common. A randomised controlled trial of acyclovir, 45 mg/kg/day by continuous intravenous infusion for 28 days versus no therapy has been completed in 30 patients positive for HBsAg and HBeAg for a minimum of 6 months. Patients were stratified for sex, histology and homosexual activity. Twenty-eight days therapy was associated with only a modest reduction in serum markers of viral replication. At 12-months DNAp was lost in 5/15 treated and 2/11 of the untreated group, while of the latter, 2 patients initially negative became positive. Seroconversion from HBeAg to anti-HBe had occurred in 4 of 15 treated and 1 of 15 untreated patients (95% confidence limits 12% and 51%) and was associated with histological improvement. Acyclovir had only a weak effect on viral replication and did not significantly accelerate the rate of seroconversion to anti-HBe.

Differential effect of ARA-AMP on serum DNA polymerase activity and serum HBV-DNA in chronic hepatitis B virus infection: A possible reason for lack of efficacy

An uncontrolled pilot study of adenine arabinoside monophosphate intramuscularly (ARA-AMP) for 5 days at 10 mg/kg/day and 23 days at 5 mg/kg/day in divided doses, was conducted in 15 consecutive patients known to be HBeAg-positive for a minimum of 12 months. Two patients were lost to follow-up (1 having developed an hepatoma). Of the remaining 13, 11 remained HBeAg-positive at 1 year. During treatment, the median serum DNA polymerase (DNAp) activity fell from 592 cpm to 203 cpm/200 microliters. Of 12 patients initially positive for DNA polymerase, complete inhibition during treatment occurred in 6 and was permanent in 2, who developed anti-HBe. In the remaining 4 and in 6 further patients in whom inhibition was substantial but incomplete, DNAp activity rose to pretreatment levels within 1 month of completing treatment. All these patients remained DNAp + HBeAg-positive at one year. Serum HBV-DNA was measured in 7 patients, 6 who were initially DNAp-positive and 4 of whom had complete inhibition of DNAp during treatment. All 7 remained positive for HBV-DNA during treatment. Although side-effects were common there were no significant changes in biochemical or haematological parameters during or subsequent to therapy. Over the subsequent 48 months 2 more patients have developed an hepatoma and a further 5 have lost HBeAg; the 4 patients who remain alive and HBeAg-positive all had chronic persistent hepatitis initially.(ABSTRACT TRUNCATED AT 250 WORDS)