iron hepatotoxicity in post-menopausal donors with hepatitis c but its absence in pre-menopausal...
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HEPATOLOGY Vol. 22, No. 4, Pt . 2, 1995 A A S L D A B S T R A C T S 4 2 7 A
1281 CHANGES IN RESPIRATORY QUOTIENT (RQ) WHILE RESTING AND DURING EXERCISE IN CIRRHOTICS WITH LONG-TERM SUPPLEMENTION OF BRANCHED CHAIN AMINO ACID (BCAA) OR PLACEBO. T. Hatori. T. Okaiima, K. Hosaka. S. Su~ano. 2nd Dept. of Internal Medicine, Toho University, Tokyo and Saiseikai Wakakusa Hospital, Yokohama, Japan
We studied BCAA's effect on RQ while resting and during physical exercise in cirrhotics. We used a treadmill with a mod, ified four-stage Bruce protocol. Measurements of oxygen consumption (VOz) and carbon dioxide production (VCO2) were taken every 3-minutes for 12 minutes. RQ was calculated from VCO2/~O 2. Subjects were 12 patients with histologically proven liver cirrhosis (LC) (age 60 :t..5, 10M, 2F, all HCV related, Child A, POz normal) and 5 healthy controls (age 65 + 10, 4M, 1F). Measurements were performed after a 3-month diet of either BCAA- enriched nutrient mixture (n=6, 150g, dally) or placebo (n=6) given orally. Dietary group assignment was double-blinded. The table summarizes the mean RQ at rest and during exercise.
RQ Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 At rest 3rain 6min 9min 12rain
Controls 0.85+0.04 0.85-+0.07 0.92+0.09 0.95+0.11 1.01+0.15 LC+placebo 0.81+0.05 0.77+0.08 0.84+0.06 0.87+0.06 0.92-+0.08 LC+BCAA 0.93+0.08 0.86+0.11 0.89+0.05 0.92+0.05 0.96+0.07
Comparisons were made by Student's t test p< 0.05 LC+BCAA vs. LC+placebo of stage 0, 1, 2 and 3
Resting RQ of the BCAA-diet-group increased significantly compared with those of the placebo-group. On exercise, a significant difference of RQ was found until 9 rain between the groups. RQ decreased temporarily at 3 rain in both groups. We found that, BCAA supplement may increase glycogen stores, the BCAA-group preferentially used glucose whereas the placebo-group used fat as an energy source.
1282 CALCITONIN THERAPY DOES NOT PREVENT TIlE EARLY BONE LOSS AFTER LIVER TRANSPLANTATION IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS OR PRIMARY SCLEROSING CHOLANGITIS. JE Hay. ER Dickson. MK Poravko. S Khosla, RH Wiesner, D Kaese, M Malinchoc. RAF Krom. Mayo-Clinic, Rochester, MN.
Liver transplantation (OLT) for chronic cholestatic liver disease is frequently complicated by worsening osteopenic bone disease; rapid bone loss and fractures are especially common in the first 6 months after transplantation. The aim of this study was to determine if calcitonin (CT), a powerful inhibitor of bone resorption, can prevent early post- OLT bone loss. Sixty consecutive consenting adults with chronic cholestatic liver disease (24 pts with PBC and 36 pts with PSC) were randomized immediately after OLT to receive (a) 100 IU salmon CT daily subeu-taneously for the first 6 months after OLT or (b) no therapy. All pts received calcium supplements and adequate vitamin D therapy to maintain normal serum levels. Bone density of the lumbar spine (BMD- LS) was measured pre-OLT, and at 4 months and 12 months after OLT by dual-energy absorptiometry. Results: 28 pts have been randomized to receive CT therapy (10 PBC, 18 PSC) and 32 pts (14 PBC, 18 PSC) assigned to the control group; the two groups were matched for age, sex, menopausal status for females, biochemical parameters of liver function and pre-OLT BMD-LS. Fifty-six pts have been followed to 4 months and 49 to 1 year post OLT.
Mean BMD-LS, g/era 2 pre-OLT 4 mos _ _ 12 mos
CT (28 pts) 0.87 0,82* 0.84 Ctrls (32 pts) 0.86 0.82* 0.84 * significantly different from pre-OLT values
Conclusions: Post-OLT therapy with salmon CT is ineffective in preventing the early bone loss after liver transplantation and treated patients showed the same pattern of bone loss and recovery as the control group.
1283 PYRIDINOLINE COLLAGEN CROSS-LINKS IN THE LIVERS FROM PATIENTS WITH CHRONIC VIRAL HEPATITIS AND
CIRRHOSIS. A Havasaka 1, S Iida 2, N Suzuki 5, F Kondo 3, M
Mivazaki 4, H Yonemitsu 2 and M Ohto 1.1 First Department of Medicine;
2Department of Laboratory Medicine; 4Second Department of
Pathology; 5First Department of Surgery, Chiba University School of
Medicine, Chiba; and 3Department of Medicine, Kimitsu Chuo Hospital, Kisarazu, Japan.
Since collagen cross-links confer resistance to collagen degradation, the pyridinoline cross-links measurement has been reported as an important criterion in assessing the irreversibility of alcoholic and alveolar echinococosis-related liver fibrosis.To evaluate whether the extent of hepatic pyridinoline cross-links is associated with the irreversibility of viral liver fibrosis, we quantitated the extent of the pyridinoline collagen cross-links in 6 normal control livers, 75 reversible fibrotic livers with various degrees of fibrosis (chronic viral hepatitis) and 13 irreversible fibrotic livers (viral cirrhosis). Collagen and pyridinoline contents were determined by high-performance liquid chromatography. Both the contents per liver weight were increased in an order of the degree of the fibrosis Significantly high levels of pyridinoline cross-links per a collagen molecule were found in the viral cirrhotic livers (0.60 [0.46, 0.65] pmol/pmol of collagen; median [25%, 75%]) compared with those in normal livers (0.39 [0.24, 0.43], P=0.03491) But no differences were found in the levels between cirrhosis and chronic hepatitis with various degrees of fibrosis (no, 055 [051, 058]; mild, 041 [0.28, 0.68]; moderate, 0.47 [0.36, 0.56]; severe, 0.47 [040, 0.64]) The result suggests that the extent of pyridinoline cross-links of collagen may be a marker of chronic fibrosis, but seems to be a less important factor to determine the irreversibility of liver fibrosis, at least, of hepatitis virus origin
1284 IRON HEPATOTOXICITY IN POST-MENOPAUSAL DONORS WITH HEPATITIS C BUT ITS ABSENCE IN PRE-MENOPAUSAL ONES. H Hayashi, T Takikawa, N Nishimura, M Yano*. S Kato**, M Arao** Dept. of Med., Hokuriku Univ., *Third Dept, of Int. Med., Nagoya Univ. and **Dept. of Med., Inazawa City Hospital, Japan
Remarkable reduction of liver enzymes after phlebotomy is evidence of iron hepatotoxicity in chronic hepatitis C (CHC). Therefore, gender difference in CHC might be explained by iron cytotoxicity.
Blood samples of female donors with antibodies to hepatitis C virus and male ones were tested for alanine aminotransferase (ALT) activities and ferritin concentrations. First, each 100 consecutive samples were compared for the prevalence of hepatitis (ALT >__ 30 U/l). Then, subjects with hepatitis were divided into 2 groups by a ~ (< 45 yrs, > 45 yrs). The biochemical index of each group was examined by Studeht's t test. Correlations between the two indices were tested after adjustment for a normal distribution of donors with various ALT levels. When correlation was good, AALT/Aferritin was used to express iron cytotoxicity.
Hepatitis was found in 7 % in females and 19 % in males. Young females showed the lowest ferritin levels among the groups and no correlation was seen between the two indices (Table). In contrast, there was a correlation between the index of the older females and that of the male groups; correlation coefficient (r) was almost the same for the 3 groups. The ferritin levels and AALT/Aferritin of older females were lower than those of male groups.
ALT (U/l) ferrifin (ng/ml) AALT/Aferritin r females <45 yrs (n = 56) 58 + 38 47 --+ 48 not calculated 0.364 females >45 yrs (n = 54) 58+31 111+ 90 0.434 0.583 males <45 yrs (n = 73) 81 +44 227--+291 0.466 0.573 males _>_45 yrs (n = 51) 74+49 258+325 0.486 0.609
While the positive rate of antibodies in the general population is 0.83 % for females and 0.93 % for males, the prevalence of hepatitis in females is less than half that in the males. Analysis of subjects with hepatitis suggests that females with mensWaation are free from iron hepatotoxicity, but that hepatotoxicity of post-menopansal females is partially iron-dependent as in the male groups. The change with aging is due to the iron store in women after menopause. Iron load with late occurrence may explain the low prevalence of CHC in female patients.