rifampin and Cholestasis--Intrahepatic

Pruritus in cholestatic liver diseases can be a major burden and dramatically impair the quality of life of those affected. Here, we provide an update on the latest insights into the molecular pathogenesis of and novel therapeutic approaches for cholestasis-associated itch. Endogenous and exogenous small-molecule pruritogen candidates bind to their receptors on unmyelinated itch C-fibres in the skin. Candidate pruritogens in cholestasis include certain lysophospholipids and sulfated progesterone metabolites, among others, whereas total bile acid or bilirubin conjugates seem unlikely to have a dominant role in the pathogenesis of cholestasis-associated pruritus. Transmission of itch signals via primary, secondary and tertiary itch neurons to the postcentral gyrus and activation of scratch responses offer various targets for therapeutic intervention. At present, evidence-based treatment options for pruritus in fibrosing cholangiopathies, such as primary biliary cholangitis and primary sclerosing cholangitis, are the peroxisome proliferator-associated receptor (PPAR) agonist bezafibrate and the pregnane X receptor (PXR) agonist rifampicin. In pruritus of intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is recommended and might be supported in the third trimester by rifampicin if needed. Alternatively, non-absorbable anion exchange resins, such as cholestyramine, can be administered, albeit with poor trial evidence. Liver transplantation for intolerable refractory pruritus has become an extremely rare therapeutic strategy.

Topics: Cholestasis; Cholestasis, Intrahepatic; Cholestyramine Resin; Female; Humans; Pregnancy; Pruritus; Quality of Life; Rifampin

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease during pregnancy, characterized by otherwise unexplained pruritus in late second and third trimester of pregnancy and elevated bile acids and/or transaminases. ICP is associated with an increased risk of adverse perinatal outcomes for the fetus and the later development of hepatobiliary disease for the mother. Bile acids should be monitored throughout pregnancy since fetal risk is increased at serum bile acids >40 µmol/l. Management of ICP consists of treatment with ursodeoxycholic acid, which reduces pruritus. Early elective delivery is common practice but should be performed on an individualized basis as long as strong evidence supporting this practice is lacking. Mothers should be followed-up for normalization of liver function tests 6-12 weeks after delivery. Future research in large-scale studies is needed to address the impact of ursodeoxycholic acid and early elective delivery on fetal outcome.

Topics: Antifibrinolytic Agents; Bile Acids and Salts; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Female; Fetal Death; Histamine Antagonists; Humans; Labor, Induced; Nucleic Acid Synthesis Inhibitors; Pregnancy; Pregnancy Complications; Premature Birth; Pruritus; Rifampin; Ursodeoxycholic Acid; Vitamin K

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive inherited disorder characterized by intermittent episodes of cholestatic jaundice. For the patients, the disease is a physical and psychological challenge. There is no curable treatment, but symptomatic relief is described following treatment with rifampicin or plasmapheresis.. Five patients suffering from BRIC followed up for 17 years by one consultant are described. Two patients were treated with rifampicin and plasmapheresis, two with rifampicin alone, and one with plasmapheresis.. The treatments showed symptomatic relief, effect on biochemical parameters, and earlier clinical remission compared with no treatment or treatment with other substances like cholestyramine, antihistamines, and ursodeoxycholic acid.. Both rifampicin and plasmapheresis represent important therapeutic options of acute cholestatic attacks in patients with BRIC. As a noninvasive treatment, rifampicin may be the first choice.

Topics: Adult; Antibiotics, Antitubercular; Bilirubin; Cholestasis, Intrahepatic; Combined Modality Therapy; Follow-Up Studies; Humans; Male; Middle Aged; Plasmapheresis; Recurrence; Rifampin; Treatment Outcome; Ursodeoxycholic Acid; Young Adult

The treatment of cholestatic pruritus in children is reviewed.. Cholestasis is characterized by an accumulation of substances that are normally secreted in the bile. Pruritus is a well-known feature of chronic cholestasis in both adults and children and has been reported as the most incapacitating symptom in children with chronic liver disease. Traditional agents, such as antihistamines, are typically ineffective as monotherapy in controlling cholestatic pruritus. As a result, clinicians have looked to other agents, such as rifampin, phenobarbital, ursodiol, opioid antagonists, and bile-binding resins, for attaining better control of pruritic symptoms. Each agent demonstrates different levels of efficacy in pediatric and adult literature. There are no guidelines or algorithms to guide therapy with these agents for children. As a result, an agent should be selected based on the patient's concurrent diseases and current medication regimen. Cholestyramine and ursodiol are both safe and inexpensive, with documented efficacy for cholestatic pruritus in children. Because cholestatic pruritus is likely a result of multiple mechanisms, combination therapy with agents that have differing mechanisms of action might be beneficial and could capitalize on potential synergy between the agents used. Future therapy for cholestatic pruritus may include serotonin antagonists, selective serotonin-reuptake inhibitors, and leukotriene antagonists.. Depending on the underlying disease state resulting in cholestasis, phenobarbital, ursodiol, bile sequestering agents, and opioid antagonists appear to be most effective for treating pruritus related to intrahepatic cholestasis. Alternatively, rifampin appears to be the only agent with reported treatment efficacy for pruritus related to extrahepatic cholestasis.

Topics: Antipruritics; Child; Cholagogues and Choleretics; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Cholestyramine Resin; Histamine H1 Antagonists; Humans; Narcotic Antagonists; Phenobarbital; Pruritus; Rifampin; Ursodeoxycholic Acid

Recent progress has enhanced our understanding of the pathogenesis of cholestatic liver diseases. Mutations in genes encoding for hepatobiliary transport systems can cause hereditary cholestatic syndromes and exposure to cholestatic agents (drugs, hormones, inflammatory cytokines) can lead to reduced expression and function of hepatic uptake and excretory systems in acquired forms of cholestasis. In addition to transporter changes which cause or maintain cholestasis, some alterations in transporter gene expression can be viewed as hepatoprotective mechanisms aimed at reducing intrahepatic accumulation of toxic biliary constituents such as bile acids and bilirubin. Alternative excretion of bile acids via the basolateral membrane into the systemic circulation facilitates the renal elimination of bile acids into urine. Moreover, increased bile acid hydroxylation, sulfation and glucuronidation by phase I and II metabolizing enzymes renders bile acids more hydrophilic and less toxic. These molecular changes are mediated by specific nuclear receptors which are regulated by bile acids, proinflammatory cytokines, drugs, and hormones. In addition to transcriptional changes, reduced transporter protein insertion to or increased retrieval from the cell membrane as well as other mechanisms such as altered cell polarity, disruption of cell-to-cell junctions and cytoskeletal changes are involved in the pathogenesis of cholestasis. Understanding the detailed mechanisms regulating expression of transport systems and enzymes is essential for the development of novel therapeutic agents. Such future approaches could specifically target nuclear receptors thus restoring defective transporter expression and supporting hepatic defense mechanisms against toxic bile acids.

Topics: ATP-Binding Cassette Transporters; Bile Acids and Salts; Bilirubin; Cholestasis, Intrahepatic; DNA Mutational Analysis; Hepatocytes; Humans; Inactivation, Metabolic; Liver; Membrane Transport Proteins; Receptors, Cytoplasmic and Nuclear; Rifampin; Risk Factors; Syndrome; Ursodeoxycholic Acid

The etiology and the pathogenesis of different forms of hepatotoxicity are discussed; case reports are included to illustrate the importance of history-taking and examination of liver tissue in establishing a specific diagnosis. The role of alcohol as a hepatotoxin as well as an enzyme-inducing agent is stressed. Genetic factors have been identified that may determine susceptibility to alcoholism and the hepatotoxic effects of alcohol and other compounds. Some cases of drug-induced cholestasis may be explained by disturbances in the known pathways of bile acid uptake, transport, and excretion. The importance of small duct destruction in patients with progressive drug-induced cholestasis is discussed. Finally, the potential hepatic complications of some nonprescription remedies used by adherents of "alternative medicine" are described, emphasizing the relevance of thorough etiological inquiry in all patients presenting with hepatic dysfunction.

Topics: Acetaminophen; Acetylcysteine; Adenoma, Liver Cell; Adult; Amoxicillin; Anabolic Agents; Beverages; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Contraceptives, Oral; Female; Humans; Isoniazid; Liver Diseases; Liver Diseases, Alcoholic; Liver Neoplasms; Male; Nonprescription Drugs; Propylthiouracil; Rifampin

Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach.. We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool.. Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial.. Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

Topics: Antipruritics; Australia; Cholestasis, Intrahepatic; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Rifampin; Treatment Outcome; Ursodeoxycholic Acid

Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) improve symptoms and biochemical markers of liver injury in cholestatic liver diseases by largely unknown mechanisms. We aimed to study the molecular mechanisms of action of these drugs in humans.. Thirty otherwise healthy gallstone patients scheduled for cholestectomy were randomized to RIFA (600 mg/day for 1 week) or UDCA (1 g/day for 3 weeks) or no medication before surgery. Routine biochemistry, lipids, and surrogate markers for P450 activity (4beta-hydroxy cholesterol, 4beta-OH-C) and bile acid synthesis (7alpha-hydroxy-4-cholesten-3-one, C-4) were measured in serum. Bile acids were analyzed in serum, urine, and bile. A wedge liver biopsy specimen was taken to study expression of hepatobiliary ABC transporters as well as detoxification enzymes and regulatory transcription factors.. RIFA enhanced bile acid detoxification as well as bilirubin conjugation and excretion as reflected by enhanced expression of CYP3A4, UGT1A1, and MRP2. These molecular effects were paralleled by decreased bilirubin and deoxycholic acid concentrations in serum and decreased lithocholic and deoxycholic acid concentrations in bile. UDCA on the other hand stimulated the expression of BSEP, MDR3, and MRP4. UDCA became the predominant bile acid after UDCA treatment and lowered the biliary cholesterol saturation index.. RIFA enhances bile acid detoxification as well as bilirubin conjugation and export systems, whereas UDCA stimulates the expression of transporters for canalicular and basolateral bile acid export as well as the canalicular phospholipid flippase. These independent but complementary effects may justify a combination of both agents for the treatment of cholestatic liver diseases.

Topics: Biological Transport; Cholelithiasis; Cholestasis, Intrahepatic; Dose-Response Relationship, Drug; Drug Administration Schedule; Elective Surgical Procedures; Female; Follow-Up Studies; Humans; Inactivation, Metabolic; Liver Circulation; Male; Middle Aged; Preoperative Care; Reference Values; Rifampin; Risk Assessment; Severity of Illness Index; Treatment Outcome; Ursodeoxycholic Acid

Chronic cholestatic liver disease in children frequently results in severe intractable pruritus. Current forms of therapy, including cholestyramine, are usually ineffective. Therefore, a 6-wk, double-blind, crossover study was designed to test the ability of rifampin to relieve pruritus in children with chronic cholestasis. Rifampin proved effective in alleviating pruritus in all five children tested compared with a placebo-treated group. After the 6-wk study period, rifampin was continued for 6 mo, and its effectiveness was maintained. No complications resulted from rifampin use. This study and a similar study in older patients with primary biliary cirrhosis suggest that a highly effective form of therapy is available for treatment of severe pruritus in patients with chronic cholestasis. These patients must be carefully selected and frequently monitored.

Topics: Adolescent; Child; Cholestasis, Intrahepatic; Chronic Disease; Double-Blind Method; Humans; Pruritus; Randomized Controlled Trials as Topic; Rifampin

Patients with benign recurrent intrahepatic cholestasis (BRIC) suffer from recurrent episodes of cholestatic jaundice. Treatment options remain limited and are mainly symptomatic. In case reports rifampicin, plasmapheresis, and nasobiliary drainage have been reported to be effective. In this case series, we present long-term experience indicating disease-modifying effects of non-invasive treatment with rifampicin for recurrent cholestasis in BRIC type 1 (BRIC1).. We included all adult BRIC1 patients diagnosed and followed up at a single centre in Bergen, Norway. Data regarding clinical and biochemical features during BRIC attacks with and without rifampicin treatment were retrieved from medical journals and a data registry.. Five males with BRIC1 were included. Median age at diagnosis was 22 years (range 15-41). Together they had suffered from 65 cholestatic attacks (including four documented abortive attacks). Twenty-eight attacks were treated with rifampicin alone over the last 12 years; all cases showed symptomatic relief and reduction in the levels of bilirubin and alkaline phosphatase in blood. The attacks treated with rifampicin seemed to have shorter duration and were less likely to result in complications or hospitalization compared to attacks prior to the introduction of rifampicin. No side effects attributable to rifampicin were noted.. Episodic treatment of recurrent BRIC1 attacks with rifampicin seems to ameliorate severity and shorten the duration of attacks. Timely diagnosis and effective treatment are of major importance in BRIC, not only to decrease complications but also improving patients' quality of life.

Topics: Adolescent; Adult; Cholestasis, Intrahepatic; Follow-Up Studies; Gastrointestinal Agents; Humans; Male; Quality of Life; Recurrence; Rifampin; Young Adult

Topics: Adenosine Triphosphatases; ATP-Binding Cassette Transporters; Cholestasis, Intrahepatic; Humans; Mutation; Rifampin

Topics: Cholestasis, Intrahepatic; Female; Humans; Pregnancy; Pregnancy Complications; Rifampin

Topics: Cholestasis, Intrahepatic; Humans; Pregnancy Complications; Rifampin

Intrahepatic cholestasis of pregnancy is an incompletely understood disease that poses significant fetal risks, including stillbirth. Treatment of intrahepatic cholestasis of pregnancy is aimed at relieving maternal symptoms and improving fetal outcomes.. A 21-year-old gravid woman, 3 para 0111, presented at 27 2/7 weeks of gestation with severe intrahepatic cholestasis of pregnancy. Her clinical course was refractory to first-line therapy with ursodiol, and she was started on rifampin with rapid improvement of symptoms and transaminitis. Despite maternal improvement, she was delivered at 31 weeks of gestation for persistent nonreassuring fetal status.. Rifampin may be an effective adjunctive therapy for intrahepatic cholestasis of pregnancy refractory to ursodiol alone. Additional research is needed to assess short-term and long-term maternal and newborn outcomes, because fetal deterioration still occurred in spite of maternal improvement.

Topics: Cholagogues and Choleretics; Cholestasis, Intrahepatic; Drug Therapy, Combination; Female; Humans; Nucleic Acid Synthesis Inhibitors; Pregnancy; Pregnancy Complications; Rifampin; Ursodeoxycholic Acid; Young Adult

In vitro studies have suggested that 4-phenylbutyrate (PBA) may rescue missense mutated proteins that underlie some forms of progressive familial intrahepatic cholestasis. Encouraging preliminary responses to 4-PBA have been reported in liver disease secondary to mutations in ABCB11 and ATP8B1. A 4-year-old boy with Byler disease was treated with 4-PBA in the forms of sodium PBA (5 months) and then glycerol PBA (7 months) as part of expanded access single patient protocols. During this therapy serum total bilirubin fell and his general well-being was reported to be improved, although total serum bile acids were not reduced. Discontinuation of rifampin therapy, which had been used to treat pruritus, resulted in reversible severe acute liver injury that was potentially the result of phenylacetate toxicity. Interactions between 4-PBA and cytochrome P450 enzymes should be considered in the use of this agent with special attention to potential phenylacetate toxicity.

Topics: Antineoplastic Agents; Bilirubin; Chemical and Drug Induced Liver Injury; Child, Preschool; Cholestasis, Intrahepatic; Humans; Infant; Liver; Liver Function Tests; Male; Phenylacetates; Phenylbutyrates; Pruritus; Rifampin

Obstetric cholestasis is a pregnancy-related disorder associated with an adverse pregnancy outcome. It is characterized by generalized pruritus, elevated bile acids, and abnormal liver enzymes. Recent publications show that obstetric cholestasis is associated with, and likely to potentiate, the risk of developing gestational diabetes mellitus.. This case describes an unusual pattern of the disease, in which obstetric cholestasis occurred in five consecutive pregnancies with a different course of the disease in the fifth pregnancy.. A patient with recurrent cholestasis of pregnancy had worsening disease in her first four pregnancies. In her fifth pregnancy, treatment for gestational diabetes mellitus with metformin was associated with a lowering effect on bile acids and liver enzymes, indicating a possible role for metformin in the management of obstetric cholestasis.

Topics: Adult; Bile Acids and Salts; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Diabetes, Gestational; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Metformin; Pregnancy; Pregnancy Complications; Recurrence; Rifampin; Ursodeoxycholic Acid

To describe the use of combined ursodeoxycholic acid (UDCA) and rifampicin treatment in intrahepatic cholestasis of pregnancy (ICP).. A questionnaire survey of 27 women with 28 affected pregnancies identified via the UK and International Obstetric Medicine forum. The clinical case notes of women with ICP treated with combined UDCA and rifampicin therapy were reviewed, and data regarding maternal and perinatal outcomes extracted.. Serum bile acids remained high whilst taking UDCA as monotherapy. In 14 pregnancies (54%) serum bile acids decreased following the introduction of rifampicin. In 10 pregnancies (38%), there was a 50% reduction in serum bile acids. There were no adverse effects reported with either drug.. This is the first report of the use of rifampicin in ICP. The data suggest that combined treatment with UDCA and rifampicin is an effective way of treating women with severe ICP who do not respond to treatment with UDCA alone.

Topics: Bile Acids and Salts; Cholestasis, Intrahepatic; Drug Therapy, Combination; Female; Gestational Age; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Rifampin; Ursodeoxycholic Acid

Benign recurrent intrahepatic cholestasis type 1 (BRIC-1), a rare autosomal recessive disorder characterized by recurrent episodes of jaundice and pruritus, is caused by mutations in the ATP8B1 gene. Rifampicin has been reported to be an effective treatment of jaundice and pruritus in patients with BRIC. Proposed mechanisms of effect for rifampicin include enhancement of multidrug-resistance protein 2 expression, activation of the enzymes of uridine diphosphate glucuronosyltransferase 1A1 and cytochrome P450 3A4, and stimulation of 6α-hydroxylation of bile acids.. To confirm the diagnosis of BRIC-1 and demonstrate the effect of rifampicin treatment on bile acid metabolism, we analyzed the patient's ATP8B1 gene and bile acids in urine.. We detected 2 heterozygous mutations in the ATP8B1 gene, and increasing amounts of unusual bile acids such as 1β-hydroxylated cholic acid, 2β-hydroxylated cholic acid, 4β-hydroxylated cholic acid, 6α-hydroxylated cholic acid, and hyocholic acid in urine during rifampicin treatment.. We diagnosed a jaundiced pediatric patient with BRIC-1 caused by 2 novel mutations (1226delA/2210delA) in the ATP8B1 gene. Rifampicin was effective in treating cholestasis. Results of urinary bile acid analyses during rifampicin treatment in this patient, suggested that rifampicin might stimulate 1β-, 2β-, and 4β-hydroxylation of bile acids in addition to 6α-hydroxylation.

Topics: Adenosine Triphosphatases; Bile Acids and Salts; Child; Cholestasis; Cholestasis, Intrahepatic; Cholic Acid; Cholic Acids; Female; Humans; Hydroxylation; Mutation; Rifampin

The case report describes a progressive familial intrahepatic cholestasis II type Byler's syndrome with structural abnormality of the bile canalicular membrane. A child with a rare hereditary pathology,who is on the waiting list for liver transplantation, on the background of complex treatment, including diet therapy, drug therapy achieved a positive dynamics of clinical and laboratory parameters, acceleration of physical, psychomotor and intellectual development, that in general has improved the surgery prognosis and quality of life of the patient.

Topics: Child, Preschool; Cholestasis, Intrahepatic; Diagnosis, Differential; Female; Humans; Liver Function Tests; Rifampin; Syndrome; Treatment Outcome; Ursodeoxycholic Acid

Rifampicin is a well-known hepatotoxicant, but little is known about the mechanism of rifampicin-induced hepatotoxicity. The aim of this study was to characterize the expression and localization of hepatocyte tight junctions in rifampicin-induced cholestasis in mice. Cholestasis was induced by administration of rifampicin (200 mg/kg) for 7 consecutive days or treatment with a single dose of rifampicin (200 mg/kg) by gastric intubation. The expression of mRNA for hepatic zonula occludens (ZO)-1, ZO-2, ZO-3, occludin and claudin-1 was determined using RT-PCR. Localization of ZO-1 and occludin was detected using immunofluorescence. Results showed that there was an 82-fold increase in the conjugated bilirubin in serum in rifampicin-treated mice. In addition, an 8-fold increase in total bile acid in serum was observed after a seven-day administration of rifampicin. The integrity of hepatocyte ZO-1 and occludin was altered by a seven-day administration of rifampicin. Importantly, the integrity and intensity of hepatocyte tight junctions were altered as early as 30 min after a single dose of rifampicin. The expression of hepatic ZO-1 and ZO-2 mRNA was significantly decreased, beginning as early as 30 min and remaining a lower level 12 h after a single dose of rifampicin. Taken together, these results suggest that the altered integrity and internalization of hepatocyte tight junctions are associated with rifampicin-induced cholestasis.

Topics: Administration, Oral; Animals; Cholestasis, Intrahepatic; Female; Hepatocytes; Mice; Microscopy, Confocal; Rifampin; Tight Junctions

Topics: Anti-Bacterial Agents; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Dietary Supplements; Disease Progression; Female; Humans; Infant; Rifampin; Treatment Outcome; Ursodeoxycholic Acid; Vitamins

Topics: Cholagogues and Choleretics; Cholelithiasis; Cholestasis, Intrahepatic; Enzyme Inhibitors; Humans; Liver Circulation; Rifampin; Ursodeoxycholic Acid

Topics: Adult; Antitubercular Agents; Cholestasis, Intrahepatic; Diagnostic Errors; Hepatitis B; Hepatitis C; HIV Infections; Humans; Isoniazid; Male; Medicine in the Arts; Mercury Poisoning; Pyrazinamide; Rifampin; Television; Tuberculosis

Rifampicin is an effective drug against pruritus in intrahepatic cholestasis. However, there is no specific hepatic disease in which its use could cause undoubtedly biochemical improvement. The aim of this study was to describe patients with complete remission of cholestatic symptoms after rifampicin therapy.. We reported three female patients with intrahepatic cholestasis with no evidence of viral, metabolic, or autoimmune liver diseases. Total bilirubin levels ranged from 13.2 to 27.2 mg/dl (before the first treatment with rifampicin), and in all of them gamma-glutamyl transpeptidase values were within the normal range or slightly increased. Rifampicin therapy was administered orally, without any concomitant drug, with an effective dosage of 5-17 mg/kg/day.. In all patients, pruritus ceased completely and bilirubin returned to normal values. The symptoms recurred after rifampicin withdrawal on, at least, three occasions in each patient, and these symptoms were always eliminated after its reintroduction. The patients had a total of 16 cholestatic episodes during a follow-up of 8 yr, with a complete clinical recovery in all of them. Undergoing therapy with a suitable dosage of rifampicin, none of the patients had a cholestatic crisis even during a period for as long as 12 months. The diagnosis of two patients was consistent with benign recurrent intrahepatic cholestasis, and it was not well defined in the remaining.. Rifampicin may induce clinical remission, and perhaps prevent clinical relapses of intrahepatic cholestasis with normal or slightly increased levels of gamma-glutamyl transpeptidase.

Topics: Adult; Child, Preschool; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Family Health; Female; gamma-Glutamyltransferase; Humans; Pruritus; Recurrence; Remission Induction; Rifampin

Topics: Child, Preschool; Cholestasis, Intrahepatic; Humans; Jaundice; Male; Pruritus; Recurrence; Rifampin; Time Factors

The pharmacokinetics of intravenously infused hexobarbital was studied in 10 patients with intrahepatic cholestasis and in 9 with extrahepatic biliary obstruction. The results were compared with those obtained in 16 healthy young volunteers and 5 older patients with normal liver function. After infusion, the plasma concentrations showed a rapid initial decline (alpha-phase) and subsequently a slower decrease (beta-phase). The half-life of a latter phase was 323 +/- 84 min in the healthy group, 357 +/- 151 min in the patients with intrahepatic cholestasis and 344 +/- 115 min in the group with biliary obstruction; the clearances were 3.41 +/- 0.90, 4.08 +/- 1.95 and 3.81 +/- 1.97 ml x min-1 x kg-1, respectively. The differences were not statistically significant. The mean volume of the central compartment of distribution and the steady state volume of distribution were not significantly different. In two patients hexobarbital clearance during cholestasis was greater than after it had subsided. After treatment of 11 patients with cholestasis with drug metabolism-inducing agents (phenobarbital, rifampicin or phenytoin), the half-life of hexobarbital was significantly shortened and the mean value of hexobarbital clearance was more than doubled.

Topics: Adult; Aged; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Enzyme Induction; Female; Hexobarbital; Humans; Inactivation, Metabolic; Kinetics; Liver; Male; Metabolic Clearance Rate; Middle Aged; Phenobarbital; Phenytoin; Rifampin