Appendicectomy and perioperative mortality in patients with liver cirrhosis.
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Adult↗
Biomedical subjects
H Vilstrup
Publications and source records attributed to H Vilstrup.
GH decreases hepatic amino acid degradation after small bowel resection in rats without enhancing bowel adaptation.
Growth hormone (GH) treatment in short bowel syndrome is controversial, and the mechanisms of a possible positive effect remain to be elucidated. Rats were randomly subjected to either an 80% jejunoileal resection or sham operation and were given either placebo (NaCl) or biosynthetic rat GH (brGH). The in vivo capacity of urea nitrogen synthesis (CUNS) and the expression of urea cycle enzymes were measured and related to changes in body weight and adaptive growth in ileal segments on days 7 and 14. Ileal segments were examined by unbiased stereological techniques. brGH treatment decreased CUNS among the resected rats by 19% (P<0.05) and 36% (P<0.05) on days 7 and 14, respectively. The mRNA levels of urea cycle enzyme genes were not influenced by brGH treatment. brGH treatment did not increase the adaptive growth in the ileal segments. In conclusion, we found that GH treatment decreased the accelerated postoperative hepatic amino acid degradation in experimental short bowel syndrome without enhancing the morphological intestinal adaptation.
Amino Acids↗
[Positron-emission tomography of liver tumors].
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Bile Duct Neoplasms↗
Effects of laparotomy vs pneumoperitoneum on the hepatic catabolic stress response in ambulatory and stationary settings in pigs.
BACKGROUND: We recently demonstrated that laparoscopic cholecystectomy is followed by a much smaller hepatic catabolic stress response than conventional cholecystectomy. It is not known what is responsible for this difference. METHODS: Thirty pigs were randomly allocated to the following five treatment groups: (1) laparotomy, (2) pneumoperitoneum, (3) pneumoperitoneum with insertion of four trocars, (4) laparotomy, (5) pneumoperitoneum. Groups 1-3 were operated on in an ambulatory setting, whereas groups 4 and 5 were operated on in a stationary setting. Urea synthesis, as quantified by functional hepatic nitrogen clearance, and the response of stress hormones and cytokines were assessed. RESULTS: Laparotomy increased the functional hepatic nitrogen clearance by 195% (p < 0.001); pneumoperitoneum and trocars increased it by 145% (p < 0.001); and pneumoperitoneum alone increased it by 113% (p < 0. 001). The difference between laparotomy and both pneumoperitoneum groups was significant. If the stress factor of ambulatory surgery was eliminated, the increase in functional hepatic nitrogen clearance was reduced to 87% (p < 0.01) after laparotomy and 38% (NS) for animals subject to pneumoperitoneum. There were significant differences in concentrations of stress hormones, tumor necrosis factor alpha, and interleukin 8 among groups intra- and postoperatively. CONCLUSIONS: The magnitude of the postoperative hepatic stress response after laparotomy compared to pneumoperitoneum with and without insertion of trocars seems to be caused by the greater trauma to the abdominal wall. Furthermore, an ambulatory setting seems to be an important postoperative stress factor in itself.
Ambulatory Care↗
Hepatic amino- to urea-N clearance and forearm amino-N exchange during hypoglycemic and euglycemic hyperinsulinemia in normal man.
BACKGROUND/AIMS: Hypoglycemia has well-described effects on glucose metabolism, whereas the possible effects on hepatic amino nitrogen conversion in relation to muscle amino nitrogen flux are more uncertain. METHODS: We studied six healthy young male subjects three times, i.e. for 6 h in the basal state, during a 6-h euglycemic hyperinsulinemic (1.5 mU/kg/min) clamp and during a 6-h hypoglycemic (plasma glucose below 2.8 mmol/l) clamp. Alanine (2 mmol/kg body weight/h) was infused for 3 h to describe the relationship between blood amino nitrogen concentrations and hepatic ureagenesis estimated from urea urine excretion and accumulation in body water. The slope of this relationship is denoted functional hepatic nitrogen clearance (FHNC) and quantifies substrate-independent alterations in hepatic amino nitrogen degradation. In parallel, amino nitrogen balances across muscles were estimated by the forearm flux method. RESULTS: Euglycemia decreased circulating glucagon values (100+/-25 ng/l vs. 160+/-30 ng/l), whereas hypoglycemia doubled glucagon (350+/-45 ng/l, p<0.05). Hepatic nitrogen clearance (FHNC) decreased during hyperinsulinemic euglycemia (19.5+/-3.4 l/h vs. 30.6+/-5.7 l/h, p<0.01), whereas forearm net uptake of amino nitrogen increased (130+/-40 nmol/100 ml x min vs. control: -10+/-4 nmol/100 ml x min). During hypoglycemia there was a 3-fold increase in hepatic nitrogen clearance up to 83.0+/-16.8 l/h (p<0.01) and increased release of amino nitrogen from the forearm (-100+/-30 nmol/100 ml x min, p<0.01). CONCLUSION: Hypoglycemia in man induces a marked increase in hepatic amino- to urea-N clearance. This catabolic response to hypoglycemia in the liver may be of primary importance for muscle amino acid release. Our data are compatible with the notion that liver and muscle together are responsible for catabolism during hypoglycemia, and that glucagon may be the primary mediator via its effect on liver metabolism.
Adult↗
Acute non-traumatic pain increases the hepatic amino- to urea-N conversion in normal man.
BACKGROUND/AIM: Severe stress results in a catabolic state with nitrogen (N) loss via hepatic urea synthesis, and in most situations a sensation of pain. Our purpose was to establish whether pain per se upregulates liver function as to urea synthesis. METHODS: Ten healthy male volunteers were investigated on 3 occasions in a crossover design. Self-controlled electrical pain was applied to the abdominal skin for 30 min to an intensity of 8 on a visual analogue scale from 0 to 10. Next, the electric profile was reproduced during local analgesia (mepivacaine 2.5 mg/kg bw), and the pain was scored to only 0.5. Finally, there was a control experiment with no intervention. Alanine infusion (1 mmol/kg/h) was started 2 h before intervention and continued throughout the investigation. Urea-N synthesis rate (UNSR) was estimated hourly as urinary excretion corrected for accumulation in body water and gut hydrolysis. RESULTS: Pain increased the Functional Hepatic Nitrogen Clearance (FHNC) assessed by the ratio UNSR/AAN (in the 3 h following pain) by 20% (22.7+/-1.2 vs 19.0+/-0.7 l/h (control), p<0.05). FHNC during local analgesia was in between (21.1+/-1.1 l/h) but not significantly different from either of the two other experiments. Mean blood amino-N concentration (AAN) and mean UNSR were comparable in the three situations. There was no difference in serum glucagon among experiments, but pain increased serum cortisol (452+/-15 vs 233+/-20 nmol/l (control), p<0.001) and plasma adrenaline (104+/-16 vs 58+/-9 pg/ml (control), p<0.05). CONCLUSION: Acute, severe atraumatic pain induces an increase in the ability of the liver to convert amino- to urea-N, and thus acts as a catabolic stimulus via regulation of liver function. The measurements of known endocrine regulators of urea synthesis do not explain the phenomenon. The present data, however, suggest the hypothesis that the effects of pain were attenuated by local analgesia. If this is confirmed by further experiments, it would indicate a signal transmission to the liver which has not been previously described.
Acute Disease↗
Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy. EuroMap Study Group.
We studied the association between acetaminophen exposure during pregnancy and the prevalence of congenital abnormalities and fetal growth. Our study included 123 women who had received a prescription of acetaminophen during pregnancy and/or 30 days before conception and 13,329 controls who did not receive any prescription at all. We found more malformations among those who received a prescription with an odds ratio of 2.3 (95% CI 1.0-5.4), but the type of malformations did not indicate a causal link. When restricting the study to first time pregnancies, we identified 58 women who received a prescription of acetaminophen during pregnancy and 30 days before conception and 7472 controls. We found no excess risk of malformation [OR = 0.7 (95% CI 0.1-5.5)], and no evidence that acetaminophen should influence fetal growth.
Abnormalities, Drug-Induced↗
Changes in liver-derived enzymes and self-reported alcohol consumption. A 1-year follow-up study in Denmark.
BACKGROUND: The association between alcohol intake and liver disease is well known, but little is known about alcohol consumption and changes in liver-derived enzymes within 1 year. In a 1-year follow-up study we examined changes in liver-derived enzymes and their association with self-reported alcohol consumption. METHODS: We recorded liver-derived enzyme values, self-reported alcohol consumption, and potential confounder variables at base line and at a 1-year follow-up in a representative sample of 822 persons (aged 30-50 years) from the survey of The Ebeltoft Health Promotion Project in Denmark, by using questionnaires, health examinations, and blood samples. RESULTS: The prevalence of increased liver-derived enzyme values was 11.1% at base line and 11.8% at the 1-year follow-up. The incidence rate of increased liver-derived enzyme values was 5.1 per 100 person-years, and 34% of the cases of increased liver-derived enzyme values returned to normal within I year. We found an odds ratio of 4.0 for men and 8.0 for women of developing increased liver-derived enzyme values if alcohol consumption was more than 21 units a week. The risk seemed to be dose-dependent. CONCLUSIONS: The prevalence of increased liver-derived enzyme values in the population was high and increased slightly during the study period. There was a strong association between the incidence rate of increased liver-derived enzyme values and self-reported alcohol consumption in a dose-dependent relationship, also when adjusted for confounding by smoking and obesity. The persons with persistently increased enzyme values had a higher weekly alcohol consumption than the rest of the study population.
Adult↗
Acute pain induces an instant increase in natural killer cell cytotoxicity in humans and this response is abolished by local anaesthesia.
We have investigated the effect of pain without tissue injury on natural killer (NK) cell activity in peripheral blood in humans and the effect of local anaesthesia on the response. Ten subjects were investigated during two sessions. First, self-controlled painful electric stimulation was applied to abdominal skin for 30 min to an intensity of 8 on a visual analogue scale (0-10). Next, the electric intensity profile was reproduced during local anaesthesia (mepivacaine 10 mg ml-1 s.c. to a total dose of 2.5 mg kg-1). NK cell cytotoxicity was measured using a 4-h 51Cr-release assay against K562 target cells. NK cell activity increased from mean 22 (SEM 4)% (baseline) to 35 (6)% and 36 (5)% after 15 and 30 min of painful stimulation, respectively (P < 0.02). A simultaneous increase in the number of CD56+ cells in peripheral blood during pain was found. Stimulation after local anaesthesia did not change either NK cell activity or number. Parallel and significant increases in concentrations of plasma epinephrine and serum cortisol were observed. These changes were abolished by local anaesthesia. We conclude that acute severe pain without tissue injury markedly increased NK cell cytotoxicity. Local anaesthesia completely abolished this immunological and hormonal response.
Adult↗
Waist circumference and body mass index as predictors of elevated alanine transaminase in Danes aged 30 to 50 years.
INTRODUCTION: We examined whether waist circumference and waist-to-hip circumference ratio were a better predictor for elevated alanine transaminase level than body mass index. METHODOLOGY: In a cross-sectional survey we examined body mass index, waist circumference, waist-to-hip ratio, alcohol consumption, and alanine transaminase level in a random sample of 903 men and women aged 30 to 50 years from The Ebeltoft Health Promotion Project in Denmark. RESULTS: Body mass index, waist circumference and waist-to-hip ratio explained an approximate 12% variation in alanine transaminase in men and 4% in women, whereas waist-to-hip circumference ratio explained a 2% variation in women. The risk of elevated alanine transaminase level in men, calculated as odds ratio, with a body mass index (kg/m2) above 30, or a waist circumference above 102 cm, or a waist-to-hip circumference ratio above 0.9 was 9.3 (95% confidence interval [CI], 3.6-24.1), 5.6 (95% CI, 2.5-12.5) and 2.7 (95% CI, 1.3-5.3) respectively, but there was no elevated risk among women. CONCLUSIONS: Waist circumference and body mass index were both predictors in men. Waist-to-hip ratio was also a predictor in men, but not as strong a predictor as waist circumference and body mass index. No association was found in women. This difference is probably explained by differences in the accumulation of intra-abdominal adipose tissue among men and women with the same degree of obesity.
Adult↗
[Alcohol drinking patterns of the Danes 1979-1992].
A questionnaire-based interview on alcohol drinking pattern in a random sample of 4,016 men and 4,179 women in 1992 was compared to an identical interview from 1979. In coherence with alcohol sale statistics, the average alcohol intake was unchanged in the population. Nevertheless, during the period drinking patterns have changed among Danes. Thus, 20 to 39 year-olds drank less, 40 to 59 years-olds drank more, fewer Danes drank during daytime, and fewer drank on weekdays at the second survey.
Adult↗
[TIPS--a therapeutic progress in portal hypertension].
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Esophageal and Gastric Varices↗
Decreased muscle strength in patients with alcoholic liver cirrhosis in relation to nutritional status, alcohol abstinence, liver function, and neuropathy.
To study motor function quantitatively in alcoholic liver cirrhosis muscle strength, liver function, peripheral nerve function, and nutrition were assessed in 24 patients. Isokinetic strength of flexion and extension at elbow, wrist, hip, knee, and ankle and of shoulder abduction and adduction was evaluated and compared with findings in 24 matched healthy subjects. Degree of liver disease was assessed with the Child-Pugh score and the galactose elimination capacity (GEC). Nutritional status was evaluated with an estimation of lean body mass (LBM) from 24-hour urinary creatinine excretions. Peripheral nerve function was evaluated with neurological symptom and disability scores, nerve conduction studies, and quantitative sensory tests summed to obtain a neuropathy rank-sum score (NRSS) for each patient. Combined muscle strength at hip, knee, ankle, shoulder, elbow, and wrist were weakened with 34% (P < .005), 35% (P < .001), 35% (P < .01), 34% (P < .01), 29% (P < .01), and 29% (P < .02), respectively. The median Child-Pugh score was 7 (range, 5-12), and the median duration of alcohol abstinence was 90 days (range, 5-960 days). After multiple linear regression analysis including LBM, Child-Pugh score, GEC, duration of alcohol abstinence, and NRSS, only LBM was correlated to the strength at the knee (r=.79; P < .0001) and at the ankle (r=.63; P < .01). It is concluded that muscle strength is weakened substantially in alcoholic patients with liver cirrhosis and that weakness is related to the severity of malnutrition but not to the severity of liver disease, duration of alcohol abstinence, or neuropathy.
Adult↗
Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark.
Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer.
Adult↗
Risk of breast cancer in men with liver cirrhosis.
OBJECTIVE: Liver cirrhosis is associated with increased levels of estrogens, which may be causally related to breast cancer. Because background estrogen levels are lower in men than in women, an estrogen-mediated link between liver cirrhosis and breast cancer would be easier to detect in men. METHODS: Men hospitalized with liver cirrhosis in Denmark from January 1, 1977, to December 31, 1989, were followed up, through record linkage, until the end of December 1993 for the possible occurrence of breast cancer. RESULTS: A total of 11,642 men with liver cirrhosis were identified and were followed for a mean period of 4.3 yr, for a total of 49,687 person-years. Three cases of male breast cancer were observed whereas 0.75 was expected, for a standardized incidence ratio of 4.0 (95% confidence interval, 0.8-11.7). CONCLUSIONS: Cirrhosis, possibly via high levels of endogenous estrogens, increases the risk of breast cancer in men.
Breast Neoplasms, Male↗
Effects of growth hormone on steroid-induced increase in ability of urea synthesis and urea enzyme mRNA levels.
Growth hormone (GH) reduces the catabolic side effects of steroid treatment due to its effects on tissue protein synthesis/degradation. Little attention is focused on hepatic amino acid degradation and urea synthesis. Five groups of rats were given 1) placebo, 2) prednisolone, 3) placebo, pair fed to the steroid group, 4) GH, and 5) prednisolone and GH. After 7 days, the in vivo capacity of urea N synthesis (CUNS) was determined by saturating alanine infusion, in parallel with measurements of liver mRNA levels of urea cycle enzymes, N contents of organs, N balance, and hormones. Prednisolone increased CUNS (micromol . min-1 . 100 g-1, mean +/- SE) from 9.1 +/- 1.0 (pair-fed controls) to 13.2 +/- 0.8 (P < 0.05), decreased basal blood alpha-amino N concentration from 4.2 +/- 0.5 to 3.1 +/- 0.3 mmol/l (P < 0.05), increased mRNA levels of the rate- and flux-limiting urea cycle enzymes by 20 and 65%, respectively (P < 0. 05), and decreased muscle N contents and N balance. In contrast, GH decreased CUNS from 6.1 +/- 0.9 (free-fed controls) to 4.2 +/- 0.5 (P < 0.05), decreased basal blood alpha-amino N concentration from 3. 8 +/- 0.3 to 3.2 +/- 0.2, decreased mRNA levels of the rate- and flux-limiting urea cycle enzymes to 60 and 40%, respectively (P < 0. 05), and increased organ N contents and N balance. Coadministration of GH abolished all steroid effects. We found that prednisolone increases the ability of amino N conversion into urea N and urea cycle gene expression. GH had the opposite effects and counteracted the N-wasting side effects of prednisolone.
Animals↗
Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites.
This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.
Adult↗
A comparative study of scientific evaluation of abstracts submitted to the 1995 European Association for the Study of the Liver Copenhagen meeting.
OBJECTIVE: Peer review is an important part of the publication of scientific results. We analysed the peer review process of abstracts submitted to the European Association for the Study of the Liver (EASL) congress in Copenhagen in 1995. DESIGN: Comparative study. All abstracts were reviewed by all six members of the EASL scientific committee. Furthermore, each abstract was evaluated by three to six experts within 17 specific study fields, appointed by the scientific committee. All abstracts received a score on a scale from 1 to 5, one being the best. For each abstract the average was calculated for the scores of the committee members and the expert reviewers separately. MAIN OUTCOME MEASURE: Abstract score. RESULTS: There was a significant difference in the scores between the committee members, who scored 3.31 on average, and the expert reviewers, who scored 3.02 on average. Within most of the study fields the tendency was that the expert reviewers gave the highest scores. Moreover, there was a significant variation in the estimates among the individual reviewers as well as between the 2 groups of reviewers. Only 25% of the abstracts that received the best scores by the expert reviewers were classified in the same way by the committee members. The predictive value of a positive evaluation by the committee members was 0.6, the predictive value of a negative evaluation was 0.90. CONCLUSIONS: There was a considerable variation in the peer review process for abstracts submitted to the 1995 EASL congress depending on selection of reviewers. Various types of peer review strategies should be tested and evaluated to secure the highest possible scientific quality of published research results.
Denmark↗