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Biomedical subjects

J Ribalta

Publications and source records attributed to J Ribalta.

At least 37 records · Page 2Linked to original sources
PubMed1997

Progesterone metabolites and bile acids in serum of patients with intrahepatic cholestasis of pregnancy: effect of ursodeoxycholic acid therapy.

The concentrations in serum of sulfated metabolites of progesterone are known to be elevated in patients with intrahepatic cholestasis of pregnancy (ICP). The profiles of these metabolites and conjugated bile acids were analyzed in serum from 11 patients with ICP before and during administration of ursodeoxycholic acid (UDCA) (8 patients) or placebo (3 patients). The clinical condition of 7 of the patients given UDCA improved markedly, and 1 patient given placebo had a spontaneous remission of the disease. The total concentration of conjugated bile acids in the 11 patients was 25 +/- 6 micromol/L (mean +/- SEM) and decreased to 6.3 +/- 3.5 micromol/L in the 7 patients responding to treatment with UDCA. The level of 7alpha-hydroxy-4-cholesten-3-one was significantly lower (7.2 +/- 2.2 ng/mL) in patients with ICP than in healthy pregnancy (18 +/- 4.6 ng/mL) (P < .05). The concentrations of 5alpha-pregnane-3alpha,20alpha-diol mono- and disulfates decreased by 52% +/- 7.9% and 68% +/- 5.5%, respectively, in the patients responding to treatment. Similar decreases were observed for the mono- and disulfates of 5alpha-pregnane-3alpha,20alpha,21-triol and 5beta-pregnane-3alpha,20alpha-diol. The disulfate of 5alpha-pregnane-3beta,20alpha-diol showed a smaller decrease, while glucuronidated steroids were not affected. The 3alpha-/3beta-hydroxysteroid ratio and di-/monosulfate ratio decreased significantly during UDCA. The magnitudes of the changes of bile acid and steroid concentrations during UDCA were not correlated to each other. The results suggest that UDCA stimulates the biliary excretion of steroids with a 3alpha-sulfoxy group and disulfates. This effect seems to be independent of the effect on bile acid excretion, indicating the use of different transport proteins. The possibility of an effect of UDCA on the formation of the steroid sulfates cannot be excluded.

Bile Acids and Salts↗
PubMed1997

Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo.

BACKGROUND/AIMS: Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset. METHODS: Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery. RESULTS: Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52+/-42 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 micromol/l vs 55.0+/-44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery. CONCLUSIONS: Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.

Adult↗
PubMed1997

Effects of ursodeoxycholic acid on conjugated bile acids and progesterone metabolites in serum and urine of patients with intrahepatic cholestasis of pregnancy.

BACKGROUND/AIMS AND METHODS: The mechanism(s) behind the effects of ursodeoxycholic acid on serum steroid sulphate profiles in patients with intrahepatic cholestasis of pregnancy is not clear. Conjugated progesterone metabolites and bile acids have therefore been analysed in serum and urine of patients with intrahepatic cholestasis of pregnancy before and during treatment with ursodeoxycholic acid using chromatographic and mass spectrometric methods. RESULTS: The concentration of glycine-/taurine-conjugated bile acids decreased from 8.9+/-3 micromol/l (mean+/-SEM) before treatment to 1.8+/-0.6 micromol/l during treatment with ursodeoxycholic acid. The total bile acid excretion in urine decreased from 56+/-14 to 32+/-5.6 micromol/g creatinine. The proportion of cholic acid in serum and urine, and of 1beta-, 2beta- and 6alpha-hydroxylated cholic acids in urine decreased markedly during ursodeoxycholic acid while the percentages of 3alpha,12alpha-dihydroxy-3-oxo-4-cholenoic acid and chenodeoxycholic acid were unchanged. The levels in serum and excretion in urine of sulphated steroids decreased during ursodeoxycholic acid, by 45-49% for disulphates and 33-35% for monosulphates. The ratios of 3alpha- to 3beta-hydroxysteroid disulphates were lowered by ursodeoxycholic acid from 1.1 (mean) to 0.68 in serum, and from 1.2 to 0.70 in urine. The corresponding ratios for monosulphates before and during ursodeoxycholic acid were 6.9 and 4.5, respectively, in serum, and 21 and 5.2, respectively, in urine. The major monosulphates in urine, dominated by 5alpha-pregnane-3alpha, 20alpha-diol, were also conjugated with N-acetylglucosamine. The excretion of these double conjugates decreased from 27+/-8.4 to 15+/-5.3 micromol/g creatinine during ursodeoxycholic acid. In contrast to sulphated steroids, the concentrations of glucuronides were unchanged in serum and their excretion in urine tended to increase during ursodeoxycholic acid. The metabolism of ursodeoxycholic acid was similar to that described in nonpregnant subjects. In addition to metabolites hydroxylated in the 1beta-, 5beta-, 6alpha/beta and 22-positions, a 4-hydroxy-ursodeoxycholic acid was tentatively identified. This occurred predominantly as a double conjugate with glycine/taurine and glucuronic acid, as did other 4-hydroxylated bile acids of probable foetal origin. CONCLUSIONS: The results are compatible with the contention that ursodeoxycholic acid stimulates the biliary excretion of sulphated progesterone metabolites, particularly those with a 3alpha-hydroxy-5alpha(H) configuration and disulphates. The effect(s) appears to be independent of the stimulation of bile acid secretion. An effect of ursodeoxycholic acid on the reductive metabolism of progesterone cannot be excluded.

Bile Acids and Salts↗
PubMed1997

Profiles of bile acids and progesterone metabolites in the urine and serum of women with intrahepatic cholestasis of pregnancy.

BACKGROUND/AIMS AND METHODS: The etiology of intrahepatic cholestasis of pregnancy (JCP) is unknown. We have performed comprehensive chromatographic and mass spectrometric analyses of progesterone metabolites and bile acids in serum and urine of six patients in order to characterize changes that might be of importance for the development of the disease. RESULTS: Conjugated bile acids were increased in serum and urine of patients with ICP while the levels of unconjugated bile acids were similar in healthy pregnancies and ICP. Unconjugated and conjugated 7 alpha, 12 alpha-dihydroxy-3-oxo-4-cholenoic acid was excreted in urine both in healthy pregnancies and in ICP, possibly indicating a rate limitation of 3-oxo-delta 4-steroid 5 beta-reductase in pregnancy. The serum levels and urinary excretion of total sulfated progesterone metabolites were increased in ICP while the glucuronides were unchanged or low. Confirming previous results, the fraction of metabolites with 3 alpha-hydroxy-5 alpha(H) configuration was increased. The urinary excretion of 5 alpha-pregnane-3 alpha, 20 alpha-diol 3-sulfate, 20-N-acetylglucosaminide was greatly increased in ICP, as was that of 3 alpha-hydroxy-5 alpha-androstane-17 beta-carboxylic acid, assumed to be a progesterone metabolite. CONCLUSIONS: The combined results of this and previous studies are compatible with a primary change in the reductive metabolism of progesterone in ICP, resulting in increased formation of metabolites with a 3 alpha-hydroxy-5 alpha(H) configuration and a larger fraction of sulfates. There also seems to be a selective defect in the biliary secretion of sulfated metabolites, particularly disulfates.

Bile Acids and Salts↗
PubMed1997

Physicochemical changes in HDL3 after bezafibrate treatment: influence on free cholesterol efflux from human fibroblasts.

The effects of bezafibrate, a well-used fibric acid hypolipidemic agent, were investigated in 10 moderately hypertriglyceridemic patients. The aim was to quantify the physico-chemical modifications to high-density lipoprotein subfraction 3 (HDL3) induced by treatment and to assess, in vitro, the alterations in its principal physiological function, the efflux of intracellular free cholesterol. Treatment (200 mg/thrice/d for 3 months) resulted in a 48% decrease in plasma triglycerides, with an increase in the HDL cholesterol, due mainly to an increase in the HDL3 (P < 0.01). Composition analysis of HDL3 indicated an increase in cholesterol esters (P < 0.01), free cholesterol (P < 0.01), and phospholipids (P < 0.01), coupled with a decrease in the protein content of the molecule compared with pretreatment values. Fluorescence anisotropy at 24 degrees C was significantly higher post-treatment than pretreatment (P < 0.01). The cholesterol effluxing capacity of pretreatment HDL3 was 28%, and post-treatment this increased to 50% (P < 0.01). Multivariate analyses indicated that the increased capacity of HDL3 to promote free cholesterol efflux was, in part, due to increased HDL3 phospholipid content and a more adequate fluidity of the molecule. These findings suggest that bezafibrate induces a lowering of plasma triglycerides and that the resultant physico-chemical alterations of the HDL3 molecule make it more efficient as an acceptor of intracellular free cholesterol.

Adult↗
PubMed1997

A variation in the apolipoprotein C-III gene is associated with an increased number of circulating VLDL and IDL particles in familial combined hyperlipidemia.

Detailed plasma lipoprotein analyses were conducted on 16 familial combined hyperlipidemic (FCHL) probands, all their available family members (n = 106) together with 12 normolipidemic control families (n = 68), and the results were assessed in relation to a C1100-T polymorphism in exon 3 of the apoC-III gene. The frequency of the T1100 genotype (CT+TT) was significantly elevated in the probands relative to control subjects (0.64 vs. 0.36; P < 0.01) and was associated with elevated concentrations of plasma triglyceride (P < 0.02) and apoC-III (P < 0.03), VLDL cholesterol (P < 0.005), VLDL triglyceride (P < 0.009), IDL cholesterol (P < 0.01). and IDL triglyceride (P < 0.007). The T1100 genotype was also associated with elevations in VLDL-apoB (P < 0.005) and IDL-apoB (P < 0.04) indicating a relationship between this variation and an increased number of triglyceride-rich particles. These findings were confined to the hyperlipidemic members of the FCHL families and showed a strong genotype-status interaction (P < 0.001). It is considerable clinical relevance that the apoC-III gene may be acting as a modifier gene that is only expressed in the presence of other factors (e.g., increased VLDL flux, low LPL activity) and therefore may predispose those members of FCHL families carrying the T1100 allele to express the FCHL phenotype.

Adolescent↗
PubMed1997

Low plasma vitamin A concentrations in familial combined hyperlipidemia.

As many as 20% of the survivors of acute myocardial infarction present with the heritable form of hyperlipidemia, termed familial combined hyperlipidemia (FCHL). Some of the genes reported to be involved in this disorder, such as those for lipoprotein lipase (LPL) and apolipoprotein (apo) C-III, are controlled by a peroxisome proliferator-activated receptor (PPAR)/retinoic acid receptor X (RXR) regulatory system, which is retinoic acid dependent. If, as we hypothesized, the availability of retinoic acid or its precursor retinol (vitamin A) could be altered in FCHL, this could help explain some aspects of the phenotypic expression of the disease. We therefore measured plasma retinol concentrations in 30 FCHL subjects and 56 controls. Plasma retinol concentrations in FCHL subjects were significantly lower than that of control subjects (1.96 +/- 0.83 mumol/L vs 2.91 +/- 1.23 mumol/L, respectively; P < 0.0001). This novel finding of significantly decreased concentrations of plasma retinol in FCHL relative to control subjects gives support to the hypothesis that vitamin A might be involved in the expression of this disorder.

Adult↗
PubMed1997

[Hepatitis C virus infection presenting as a polyarthritis: report of 2 cases].

Several disease have been associated with hepatitis C virus infections, including rheumatologic, hematologic and neoplastic disorders. We report two women, aged 57 and 39 years old whom the initial presentation of hepatitis C virus infection was an arthritis resembling rheumatoid arthritis. Laboratory work up revealed abnormal liver function tests, stimulating the search for hepatitis C virus infection, having both patients positive ELISA tests. Detection of this agent is extremely important when selecting a therapy for the articular disease, since several drugs used in the treatment of rheumatic disorders are potentially hepatotoxic and immunosuppression is risky in the setting of a viral hepatitis.

Adult↗
PubMed1995

[Can a selenium deficiency affect the pathogenesis of cholestasis in pregnancy?].

UNLABELLED: In search of an environmental factor which modulates the expressivity of cholestasis of pregnancy and explains the seasonal and annual variations observed in Finland and Chile, the authors measured selenium (Se) concentration in the plasma and erythrocytes by atomic absorption spectrophotometry and the activity of the glutation peroxidase enzyme dependent on Se (GSH-Px) by a spectrophotometric method in 10 patients with cholestasis of pregnancy, 22 normal pregnant women, 43 non pregnant women and in 15 men, all of whom had normal weight/height, and similar ages, ethnic and geographic origin. Blood samples were obtained weekly from the pregnant women during the third trimester and 24-72 hours postpartum. RESULTS: In non pregnant women and in men plasma Se was 0.83 +/- 0.02 mumol/l (range 0.6-1.2) and the GSH-Px activity was 306 +/- 5 U/L (range 203-459). Both parameters were correlated and were similar to those of other populations whose ingestion of Se is low (Finland, New Zealand, and certain regions of China). In normal pregnant women studied between weeks 20 and 32, the plasma Se and GSH-Px activity were lower than in non pregnant women (0.71 +/- 0.02 mumol/l and 260 +/- 5 U/l, respectively) with both progressively decreasing at the end of pregnancy and rapidly recovering post partum. The erythrocytic GSH-Px activity was similar in normal pregnant women than in non pregnant women (27.7 +/- 0.8 versus 28.1 +/- 0.6 U/g Hb). In patients with cholestasis of pregnancy, plasma and erythrocytic Se and GSH-Px activity were lower than in normal pregnant women (p < 0.05 in similar stages of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

Chile↗
PubMed1995

Is dietary erucic acid hepatotoxic in pregnancy? An experimental study in rats and hamsters.

The hypothesis that dietary erucic acid may contribute to the pathogenesis of intrahepatic cholestasis of pregnancy has been examined in pregnant rats and hamsters after prolonged feeding of diets containing 25% rapeseed oil rich in erucic acid (40% of fatty acids) or corn oil, without erucic acid. Both dietary oils were well tolerated, although weight gain was 17% to 20% less in animals receiving rapeseed oil. Rats and hamsters were studied on the last day of pregnancy and compared with age- and diet-matched nonpregnant animals. Histological examination showed no major morphologic abnormalities in liver, heart, kidneys, and adrenals. Similar microscopic deposits of fat were found in the livers and hearts of pregnant hamsters of both dietary groups. Chromatographic analysis of fatty acids in liver, heart, and kidney homogenates of hamsters and in isolated rat liver cells reflected the fatty acid composition of the dietary oils: oleic (18:1) and linoleic (18:2) acids were among the predominant fatty acids. Erucic acid was found in a higher proportion in the heart (14% by weight of total fatty acids) than in the liver (3%) and kidneys (3%) of animals fed rapeseed oil. Bile flow and biliary lipid composition was similar in rats and hamsters fed rapeseed or corn oil. Bile flow tended to be less in pregnant than in nonpregnant animals. Pregnant hamsters fed rapeseed oil tended to have the lowest bile flow. The lithogenic index of bile was slightly decreased in pregnant rats and increased in pregnant hamsters, although these proportional changes were similar for both diets. In all circumstances the lithogenic index remained below a value of 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Acute fatty liver of pregnancy: a clinical study of 12 episodes in 11 patients.

Twelve episodes of acute fatty liver of pregnancy (AFLP) were diagnosed in 11 patients during the past 18 years in a general hospital in Santiago, Chile, with a prevalence of 1 per 15,900 deliveries. Acute fatty liver of pregnancy started between the 31st and 38th weeks of pregnancy, with malaise, vomiting, jaundice, and lethargy as the main clinical manifestations. Polydipsia (in nine episodes) and skin pruritus (in seven episodes) were unusual clinical findings. In two patients, pruritus started two and four weeks before AFLP, suggesting that an intrahepatic cholestasis of pregnancy preceded AFLP in those patients. Considering the current prevalence of both diseases in Chile, their association should be considered fortuitous. In another patient, two consecutive pregnancies were affected by AFLP, raising to three the number of reported patients with recurrent AFLP. In 11 episodes, liver biopsies supported the diagnosis of AFLP by showing small and midsized vacuolar cytoplasmic transformation as the most prominent histopathological feature. Positive intracellular fat staining was found in the four samples analysed. Studies by electron microscopy showed megamitochondria with paracrystalline inclusions in four samples. All the mothers survived, but fetal mortality was 58.3%. Several extrahepatic complications delayed maternal recovery for up to four weeks after delivery. This study confirms an improvement in maternal prognosis in AFLP, discusses the possibility of an epidemiological association with intrahepatic cholestasis of pregnancy, and increases the number of patients reported with recurrent AFLP.

Acute Disease↗
PubMed1992

Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy.

The efficacy and safety of ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy was investigated in an open pilot study. Five patients received 1 gm/day of ursodeoxycholic acid during 20 days and another three patients received two identical periods of treatment separated by a 14-day interval free of the drug. Pruritus and serum levels of total bile salts and glutamic-pyruvic transaminase improved significantly during treatment with ursodeoxycholic acid. In the three patients who received two periods of treatment with ursodeoxycholic acid, pruritus and the laboratory alterations relapsed in the second week after the drug was discontinued, but they improved again when ursodeoxycholic acid was readministered. No adverse reactions were detected in the mothers or in their babies. All newborns were thriving normally during a follow-up period that lasted 5 mo after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its promising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials.

Adult↗
PubMed1992

[Symptomatic effect of epomediol in patients with cholestasis of pregnancy].

Epomediol is a terpenoid that prevents and reverses cholestasis induced by ethinylestradiol in the rat, apparently by improving liver cell membrane fluidity. Assuming that the pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is related with increased estrogen levels, we studied the effects of epomediol in this disease. Patients hospitalized due to ICP received epomediol 900 mg/day (n = 7), or 1,200 mg/day (n = 4) orally, during 15 days. Biochemical parameters of liver dysfunction (serum bilirubin, bile salts, aminotransferase, alkaline phosphatases) were not modified during nor after epomediol administration. The severity of pruritus was significantly reduced in comparison to pretreatment status, with both doses of epomediol. A greater amelioration of pruritus was observed in patients treated with epomediol 1,200 mg/day than in patients who received 900 mg/day (to 20.7 +/- 6.2, as percent of pre-treatment severity score, versus 48.8 +/- 7.5 respectively; p < 0.05). After epomediol administration was stopped, pruritus relapsed in 6 patients; 3 of them had received the higher drug dose. After delivery, pruritus vanished and liver function tests returned to normal, in all patients. No adverse effects attributable to the drug were observed in the mothers or in their babies. The beneficial effect of epomediol on pruritus in patients with ICP appeared greater in this study than that observed recently in similar patients who received a placebo.

Bile Acids and Salts↗
PubMed1991

[Effects of ursodeoxycholic acid in patients with cholestasis of pregnancy].

In an open, pilot study, the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy was investigated. Four patients received 1 g/day of UDCA during 20 days and another 2 patients received 2 identical periods of treatment separated by a 14-day interval free of drug. Pruritus and serum levels of total bile salts and glutamic-pyruvic transaminase improved significantly during treatment with UDCA. Although pruritus and the laboratory alterations had a relapse in the second week after UDCA was discontinued, they improved again in the 2 patients who received a second treatment with UDCA. No adverse reactions were detected in the mothers or in their babies. All newborns are thriving normally, in a follow-up that lasted 3 to 6 months after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its promising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials.

Adult↗
PubMed1991

S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results.

S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy.

Apgar Score↗
PubMed1990

[Primary biliary cirrhosis. The clinical experience in 31 patients].

We analyzed 31 patients with a diagnosis of primary biliary cirrhosis, 29 of them males, aged 23 to 72 years. Liver biopsy was diagnostic in all showing initial findings of the disease in 5. Echotomography and cholangiography demonstrated a patent biliary, tract. Anti-mitochondrial antibodies were present in 94% of patients. Alkaline phosphatase and biliary acid levels were useful for diagnosis. Pruritus was present with varying intensity in all patients, with premenstrual exacerbations in 5 females who had cholestasis of pregnancy or hepatitis caused by progestin drugs before developing cirrhosis. Recurrent urinary tract infection was present in 8 patients, osteoporosis in 24, Sjogren's syndrome in 24 and Crest syndrome in 4. Survival ranged from 1 to 12 years, death being caused by ruptured esophageal varices in 12 patients and by liver failure in 7. Persistence of pruritus and altered liver function tests after cholestasis of pregnancy or hepatitis caused by progestins should lead to investigation of biliary cirrhosis.

Adult↗