Long term response to therapy of chronic anti-HBe-positive hepatitis B is poor independent of type and schedule of interferon.

OBJECTIVE: The response rate to alpha interferon (IFN) of chronic anti-HBe-positive hepatitis B is variable. We studied whether type, dose, and schedule of IFN, and type and frequency of posttreatment monitoring, influence the response rate. METHODS: Seventy-two consecutive anti-HBe-positive chronic hepatitis B patients (59 male and 13 female, median age 41 yr) stratified by sex and histology were randomly allocated to three treatment arms. Twenty-seven patients (A) received 10 million units alpha-N1 IFN i.m. t.w. for 24 wk (total dose: 720 million units); 21 (B) received 9 million units alpha-2a IFN i.m. t.w. for 4 wk, followed by 18 million units for 12 wk and 9 million units for 8 wk (972 million units); 24 (C) received 2 alpha-2a IFN courses (9 million units i.m. t.w. for 16 and 12 wk separated by a 6-month interval [756 million units]). Primary response was defined by normal ALT and serum HBV-DNA levels below 10 pg/ml at the end of therapy and sustained response by normal ALT (tested monthly), undetectable HBV-DNA and IgM anti-HBc (<7 I.U. Paul Ehrlich Institute) (tested every 3 months) during the posttreatment follow-up. RESULTS: At the end of treatment, 12, 8, and 13 patients from groups A, B, and C, respectively, were responders. At the 18-month follow-up, two patients in group A and only one in groups B and C maintained the response. Overall, after 34 months (median posttreatment follow-up), three patients were long term responders, whereas three showed a sustained remission after relapse. CONCLUSIONS: The rate of long term response to interferon of anti-HBe-positive chronic hepatitis B is poor, independent of IFN type, dose, or schedule; the more stringent the monitoring, the higher the relapse rate.

Metabolism of odd-numbered, normal fatty acids in Tetrahymena pyriformis W.

Tetrahymena pyriformis W cells were grown with short- and long-chain, odd and even normal fatty acid supplements. Tris acetate addition had no effect on the fatty acyl composition of the glycerophospholipids or sphingolipids, while Tris propionate supplementation led to a marked increase in odd normal fatty acids at the expense of even normal acids in both classes of complex lipids. This enhancement of odd normal acids permitted the identification of 17:1 delta 9(n), 17:2 delta 6,9(n), 17:2 delta 9,12(n), 17:3 delta 6,9,12(n), 19:1 delta 9(n), 19:2 delta 9,12(n) and 19:3 delta 6,9,12(n) by oxidation with periodate-permanganate and examination of the short-chain fragments. Supplementation with pentadecanoic acid (15:0(n)) led to an increase in the proportions of normal C15, C17 and C19 acids. The increase in C15 acids primarily reflected a rise in 15:0(n), whereas the rise in the levels of C17 and C19 acids was accounted for by an elevation of unsaturated acids. Growth with heptadecanoic acid (17:0(n)) resulted in substantial increases in unsaturated normal C17 and C19 fatty acids, while nonadecanoic acid (19:0(n)) addition led only to an increase in the proportion of unsaturated C19 acids. Retroconversion of these saturated, odd normal long chain fatty acid supplements was limited. Supplementation with arachidic acid (20:0(n)) resulted in only a marginal increase (1.4%) in normal C20 fatty acids of both the glycerophospholipids and the mild alkali labile neutral lipids and provided no evidence that desaturation occurred. The release of 14CO2 from [1-14C]arachidic acid when incubated with the ciliates indicated that this long-chain saturate is accumulated, activated and degraded. Normal C16-C19 saturated fatty acids are substrates for the delta 9 desaturase. The delta 11 isomers arise by chain elongation. Normal C16-C19 delta 9 monoenoic acids are substrates for the delta 12 desaturase. Normal C16-C18 delta 9 monoenes, normal C16-C19 delta 9,12 dienes and 18:1 delta 11(n) are desaturated at the C-6,7 position.