Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials.

OBJECTIVES: To determine the safety and efficacy of rifampin for treatment of pruritus associated with cholestasis due to chronic liver disease. METHODS: Medical literature was searched systematically using keywords as rifampicin, rifampin, rifamycin, cholestasis, pruritus, itching, and liver disease. Trials that compared the efficacy of rifampin with placebo/alternative for treatment of pruritus due to chronic cholestasis were selected for analysis. Primary outcomes were resolution of pruritus and development of side effects. Association was measured with the odds ratio (OR). Breslow-Day method was used to treat for homogeneity under null hypothesis that OR was consistent across all the trials. Corrected Mantel-Haenszel chi(2) test was used to test if OR differed systematically from value of 1. RESULTS: Five prospective randomized-controlled cross-over trials with 61 patients were identified. Treatment with rifampin led to complete or partial resolution of pruritus in 47 (77%) patients as compared with 12(20%) treated with placebo or alternative (OR 15.2, 95% confidence interval 5.2-45.6, P=0.001). Four (7%) patients treated with rifampin suffered side effects, which resolved after its discontinuation. There was no incidence of hepatotoxicity. Test of heterogeneity for primary end points among the trials was not significant (P=0.16). CONCLUSION: This meta-analysis suggests that rifampin is safe and effective for treatment of pruritus due to chronic cholestasis. This analysis also suggests that use of rifampin for short duration is associated with a low risk of hepatotoxicity.     

Successfully treated intractable pruritus with rifampin in a case of benign recurrent intrahepatic cholestasis

A 56-year-old gentleman with benign recurrent intrahepatic cholestasis (BRIC) suffered from recurrent episodes of pruritus for over 40 years. The treatment prescribed, namely cholestyramine, was minimally effective. However, rifampin 150 mg b.i.d promptly and completely relieved his severe pruritus. The diagnosis of BRIC, being a rare condition, may go unrecognized. The severity of the lifelong episodes of intermittent cholestasis with pruritus in BRIC may be extremely distressing to the affected patient. Administration of rifampin during the acute episode of severe pruritus led to a marked improvement in his quality of life.     

Pilot study of bright-light therapy reflected toward the eyes for the pruritus of chronic liver disease

OBJECTIVE: It is proposed that the pruritus of cholestasis is, in part, centrally mediated by endogenous opioid peptides. The expression of these peptides and their receptors on neurons displays a circadian rhythm, as does the scratching activity in patients with cholestasis and pruritus. Because light has regulatory effects on circadian rhythms via retinothalamic pathways, we hypothesized that bright-light therapy (BLT) reflected toward the eyes might alter the pruritus of cholestasis. To test this hypothesis, we studied the effect of BLT on this form of pruritus. METHODS: Eight patients with chronic liver disease of different etiologies and pruritus were studied in an open-label, pilot study of 8-wk duration. BLT (10,000 lux) was administered for up to 60 min twice a day. Pruritus was assessed subjectively by a visual analog scale from which a visual analog score (VAS) was derived, and objectively, by a scratching activity monitoring system that recorded hourly scratching activity (HSA). RESULTS: In seven of the eight patients studied, the mean HSA was lower during BLT. BLT was associated with a mean decrease in HSA of 32.2% (p = 0.123). The mean VAS for pruritus was lower in six patients during BLT; the mean VAS score derived from the eight patients studied decreased by 42% (p = 0.05) during treatment. CONCLUSIONS: The results of this short-term study suggest that the pruritus of cholestasis is responsive to bright light reflected toward the eyes and that in some patients, BLT may ameliorate this form of pruritus.     

Treatment of pruritus of primary biliary cirrhosis with rifampin

Pruritus can be a debilitating symptom in patients with chronic cholestasis. Based on previous reports of its efficacy, we evaluated the impact of rifampin on the pruritus associated with primary biliary cirrhosis. Fourteen patients were included in a randomized, crossover study. After a 15-day washout period, subjects were followed for three weeks. During the first and third week, patients received 600 mg of rifampin or placebo; no treatment was administered during the second week. Pruritus was subjectively scored on a scale from 0 to 100. With rifampin, pruritus disappeared in 11 patients and partially improved in three; with placebo, only two had a partial response (P<0.001). Six patients with a prior poor or no response to cholestyramine improved with rifampin. No changes in biochemical tests or side effects were observed during this period. We conclude that short-term administration of rifampin relieves pruritus in primary biliary cirrhosis. When administered over a period of eight months in an open study, the relief of pruritus was maintained, while one individual developed an allergic reaction. Rifampin appears to be a safe drug in the management of the pruritus of primary biliary cirrhosis.     

Florid opioid withdrawal-like reaction precipitated by naltrexone in a patient with chronic cholestasis

Findings consistent with the hypothesis that increased central opioidergic tone contributes to the pruritus of cholestasis provide a rationale for treating this form of pruritus with opiate antagonists. However, initiation of therapy with an opiate antagonist in a cholestatic patient may precipitate a transient opioid withdrawal-like reaction. A woman with chronic cholestasis and disabling pruritus experienced severe transient opioid withdrawal-like reactions after oral administration of 12.5 and 2 mg naltrexone. Subsequently, naloxone was administered by intravenous infusion. Initially, the infusion rate was low and subtherapeutic. It was gradually increased to a rate known to be effective in inducing opioid antagonism. Oral naltrexone was then reintroduced without any reaction occurring. During the ensuing 12 months, while taking naltrexone, 25 mg daily, the patient has been completely free from pruritus. These observations strongly support the hypothesis that increased central opioidergic tone is a component of the pathophysiology of cholestasis.     

Pruritus of unknown origin and elevated total serum bile acid levels in patients without clinically apparent liver disease

Background and Aim: Generalized pruritus of unknown origin (PUO) is a highly distressing condition that is unrelated to any underlying dermatologic or systemic disorder (e.g. cholestasis). Little is known about the potential contribution of elevated total serum bile acid (TSBA) levels to PUO. Our aim in the present study was to investigate the role of elevated TSBA levels in patients with PUO and the efficacy of ursodeoxycholic acid (UDCA) and cholestyramine therapy. Methods: Retrospective study comprising 117 patients with chronic pruritic conditions (PUO, atopic disease, asteatotic eczema, latent cholestasis, etc.); 99 patients with available TSBA levels were included and compared with healthy controls. Results: Elevated TSBA levels were detected more frequently in patients with chronic pruritic diseases than in the control population (28.28% vs 6%; P < 0.001) with significantly higher pathological absolute levels (mean 17.45 ± 34.46 µmol/L vs 6.02 ± 4.73 µmol/L; P = 0.001). Patients with PUO (n = 18) showed the second‐highest prevalence of pathological bile acid level elevation (83.3%; control population 6%; P < 0.001), after patients with subclinical cholestasis and presented with particularly high TSBA serum values (mean 37.79 ± 53.38 µmol/L; P < 0.001). Cholestyramine (n = 9) and UDCA (n = 8) therapy were both effective in lowering TSBA levels and lead to substantial improvement of pruritus in patients with elevated TSBA levels. Conclusions: Total serum bile acid levels are elevated in a high proportion of patients with PUO. These results provide evidence of a potential involvement of subclinical cholestasis in the pathogenesis of PUO. We suggest that evaluation of TSBA levels should be included in the diagnostic work‐up of patients with chronic unexplained pruritus.     

Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis

Partial diversion of bile flow to an external stoma was performed in 6 patients with chronic intrahepatic cholestasis with severe pruritus that had been refractory to medical measures. Four patients with progressive intrahepatic cholestasis and 2 with arteriohepatic dysplasia were treated. Follow-up has been 3-8 yr. Patients with progressive intrahepatic cholestasis have been free of itching since surgery. Serum bile salt concentrations fell from 218-275 microM (normal less than 10) before to less than 10 microM after surgery. Biochemical tests of liver function and histology returned to normal or near normal. Patients with arteriohepatic dysplasia had persistent mild pruritus after surgery. Serum bile salt concentrations fell from 153-317 to 25-37 microM. There was little or no improvement in biochemical tests or histology. Bile volume and bile salt diverted were higher in patients with progressive intrahepatic cholestasis (7.3-13.0 ml/kg.day and 83-137 mumol/kg.day, respectively) than those with arteriohepatic dysplasia (3.2-4.5 ml/kg.day and 21-36 mumol/kg.day). The quality of life since surgery has been excellent in patients with progressive intrahepatic cholestasis, but not as optimal in those with arteriohepatic dysplasia. These findings suggest that partial external biliary diversion can provide effective relief from pruritus and perhaps reversal of liver disease in patients with progressive intrahepatic cholestasis. It should be used in patients with arteriohepatic dysplasia only in those with disabling pruritus.     

Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5‐year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.     

Treatment of primary biliary cirrhosis

Primary biliary cirrhosis is a chronic liver disease of unknown etiology, characterized by inflammation and destruction of the intrahepatic biliary ducts, resulting in chronic cholestasis and eventually cirrhosis. The main clinical manifestations consists of pruritus, jaundice, xanthomas, and the consequences of intestinal malabsorption, including vitamin deficiencies and osteodystrophy. Treatment of PBC is addressed at preventing or relieving the symptoms and clinical consequences of chronic cholestasis, and also at correcting the bile duct abnormalities by specific treatments. Pruritus is treated with cholestyramine, but in some cases other drugs, such as rifampicin or opioid antagonists are needed. Bisphosphanates are effective for increasing bone mass in osteopenic patients. Vitamin D and cAlcium supplements are also recommended, particularly in patients with severe cholestasis. Ursodeoxycholic acid (UDCA) has become the standard treatment (13-15 mg/kg/day), resulting in marked relieving of cholestasis. UDCA also prevents the histological progression of the disease, although the effects on survival are less apparent. Small trials of combination therapy using UDCA with methotrexate, colchicine, or prednisone, have been reported but have not shown any increased efficacy over UDCA therapy. Liver transplantation is the only treatment available when cholestasis progresses, with very good survival rates.     

Failure of rifampin to relieve pruritus in chronic liver disease

We investigated the effect of rifampin on pruritus in 12 patients with chronic liver disease: non-A, non-B hepatitis (n = 3), alcoholic cirrhosis (n = 4), primary biliary cirrhosis (n = 4), and primary sclerosing cholangitis (n = 1). The study was a crossover, randomized, double-blind trial where placebo and drug were given daily in identical capsules (300 mg) for 2 weeks each, with a 1 week washout before and after each cycle. Mean duration of pruritus was 1.6 years (range of 4 months-5 years). Blood tests were done weekly and patients used a visual analogue scale (VAS) from 0 to 100 to mark their level of itchiness daily. Only transaminases were significantly lower while the patients were on rifampin. VAS scores were minimally affected by either rifampin or placebo. At the end of the trial, four patients said they were less itchy on rifampin and three preferred placebo. Of these seven patients, small falls in VAS scores occurred in two patients on rifampin and two on placebo; there was no change in the remaining three. There was little change in serum bile salt levels during the trial. No patient became jaundiced and deepening of jaundice did not occur in the four patients with initially elevated bilirubin. We conclude that a daily 300 mg dose of rifampin was not effective in relieving pruritus in a variety of chronic liver diseases.     

Ondansetron and pruritus in chronic liver disease: a controlled study

BACKGROUND/AIMS: Increased central opioidergic neurotransmission, mediated by endogenous opioid peptide agonists, contributes to the pruritus of cholestasis. There are interrelationships between the opioid and serotonin neurotransmitter systems. The serotonin 5-HT3 receptor subtype antagonist, ondansetron, has been reported to ameliorate centrally-mediated pruritus induced by exogenously administered opiates. This study was designed to determine whether long-term oral administration of ondansetron is efficacious in ameliorating pruritus complicating chronic liver disease. METHODOLOGY: Seventeen patients with severe pruritus complicating established chronic liver disease were randomized to receive, double-blind, ondansetron (8 mg) or a placebo orally; each was administered thrice daily for a 4-week period. Endpoints were subjective scores of pruritus and objective 24-hour measurements of scratching activity. Analysable data were generated in 13 of the patients. RESULTS: Ondansetron therapy was associated with ameliorations of pruritus that appeared to be clinically significant in 5 patients (38%); in these 5 patients the mean decrease in a subjective score of pruritus was 27% of the scale of the score. However, these apparent ameliorations were not associated with robust decreases in scratching activity. For the whole group of 13 patients mean scratching activity during ondansetron therapy was not significantly less than that during treatment with placebo (p = 0.19). The total time that patients were not scratching was similar during treatment with ondansetron and placebo (p = 0.57). CONCLUSIONS: The findings suggest that serotoninergic neurotransmission, in neurons bearing receptors of the 5-HT3 subtype, plays no more than a minor role in the mediation of pruritus complicating chronic liver disease. The lack of an association between the results of applying subjective scores of pruritus and scratching activity emphasizes the need to include an objective quantitative efficacy endpoint in the design of trials of new therapies for pruritus.     

Review: Treatment of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a slowly progressive chronic cholestatic disease of the liver thought to be caused by immune destruction of the interlobular bile ducts. One-third of patients are asymptomatic and one-third of these develop symptoms within 5 years. Therapeutic regimens should be directed at the control of symptoms, prevention of complications and specific therapy aimed at controlling progression of the disease. Symptoms may be secondary to cholestasis or due to other associated diseases. The cause of pruritus secondary to cholestasis remains unknown; the anion exchange resin cholestyramine generally brings relief. In patients resistant or intolerant to this therapy, rifampin may be helpful, as well as ultraviolet light without sunblock. Liver transplantation may rarely be the only option for uncontrollable pruritus. Clinical manifestations of keratoconjunctivitis sicca and xerostomia need constant attention to prevent corneal ulcers and dental caries. Preventative therapy includes regular screening for thyroid dysfunction and replacement therapy when necessary and the administration of the fat soluble vitamins A, D and K once hyperbilirubinaemia is present. Osteoporosis is a complication of all cholestatic liver disease. There is no satisfactory preventative therapy. It may be appropriate to give hormone replacement therapy to all post-menopausal women with PBC to reduce osteoporosis. Liver transplantation is the best option for those with fractures. Oesophageal varices may develop early in the course of PBC, non-selective beta-blocker therapy should be used as prophylaxis against variceal haemorrhage. The only specific therapy shown to cause both a biochemical and survival benefit in patients with PBC is ursodeoxycholic acid (UDCA). Treatment with UDCA delays progression, but does not result in a cure of this disease. Currently, liver transplantation is the only definitive treatment available for end-stage disease.     

Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-alpha-tocopheryl polyethylene glycol-1000 succinate

Treatment of vitamin E deficiency during chronic childhood cholestasis is hampered by the poor intestinal absorption of available oral preparations of vitamin E when bile flow is severely impaired; thus parenteral vitamin E has been the only effective therapy for many children with this problem. We studied the intestinal absorption, efficacy, and safety of a water-soluble oral form of vitamin E, d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), in 22 children (7 mo to 19 yr old) with severe cholestasis and vitamin E deficiency who were unresponsive to massive oral doses (100-200 IU/kg.day) of dl-alpha-tocopherol. The results of oral vitamin E tolerance tests showed that TPGS was well absorbed in virtually all study subjects, that TPGS intestinal absorption was superior to that of dl-alpha-tocopherol, and that TPGS absorption in teenage children with chronic cholestasis was similar to that of normal adults. In addition, 1.7% +/- 1.6% (mean +/- SD) of the administered polyethylene glycol 1000 contained in the TPGS was absorbed and excreted in the urine of the 13 subjects analyzed, compared with 3.0% +/- 1.3% in 4 normal adults. A chronic oral dose of 15-25 IU/kg.day of TPGS corrected the biochemical vitamin E deficiency state over 1-19 mo (mean, 10.6 mo) of TPGS therapy. No clinical or biochemical evidence of gastrointestinal, renal, hepatic, or hematologic toxicity was demonstrated. This study suggests that TPGS administered orally in a dose of 15-25 IU/kg.day may be a safe and effective form of vitamin E for prevention and correction of vitamin E deficiency during severe childhood cholestasis.     

Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial

The cause of pruritus of cholestasis is unknown. We have hypothesized that pruritus may be caused by an indirect effect of high hepatic concentrations of toxic bile acids. To test this hypothesis, we have conducted a double-blind, controlled, crossover clinical trial of rifampin, an agent that inhibits hepatic bile acid uptake and may detoxify hepatic bile acids by stimulation of mixed-function oxidases. Nine patients with primary biliary cirrhosis received 300-450 mg/day of rifampin and placebo sequentially, in random order. Each treatment was administered for 14 days, with a 14-day washout between treatments. Endpoints included patient preference, changes in a daily visual analogue scale pruritus score, and amount of cholestyramine ingested. Antipyrine elimination rates and serum bile acids were tested at the end of each treatment period. All 9 patients completed the trial and 8 of them preferred rifampin to placebo (p = 0.03). There were no adverse reactions. Visual analogue scale pruritus scores showed no significant placebo response or any effect from the order of treatment, but did show a highly significant reduction in pruritus in response to rifampin (p less than 0.002). This effect was evident within the first week of rifampin treatment. Rifampin produced a 33% reduction in antipyrine plasma half-life, but no change in fasting total serum bile acids. Cholestyramine usage did not change significantly. We conclude that rifampin is useful for short-term relief of pruritus in primary biliary cirrhosis; however, the mechanism of this effect is unknown. Longer trials are needed, as are trials in other cholestatic disorders.     

Role of plasmapheresis in the treatment of severe pruritus in pregnant patients with primary biliary cirrhosis: case reports.

BACKGROUND: Primary biliary cirrhosis (PBC) may be associated with pruritus and, when present, may be accentuated during pregnancy. Several therapeutic modalities have been used to control itching caused by cholestasis, with variable responses. Drug therapies are ill-advised, particularly in early pregnancy. Plasmapheresis has been successful in controlling pruritus in patients with cholestasis. The use of plasmapheresis to alleviate severe life-threatening pruritus during pregnancy is reported in two patients with PBC. CASE PRESENTATIONS: Two patients with PBC presented during their second trimester of pregnancy with severe pruritus that did not respond to the anion exchange resin cholestyramine. Their symptoms were disabling to the point that one patient had suicidal ideation. Given the severity of their symptoms, multiple sessions of plasmapheresis were instituted with good control of pruritus. Both patients tolerated the procedure well and delivered healthy babies. CONCLUSION: Plasmapheresis is a relatively safe and rapidly effective treatment for severe pruritus during pregnancy in patients with PBC.     

Evaluation of the role of bile acids and serotonin as markers of pruritus in children with chronic cholestatic liver disease

Background and study aimsPruritus is an annoying symptom with an unclear pathogenesis accompanied by chronic cholestasis. This cross-sectional study was conducted to define the relationship between serum levels of presumed pruritogens (bile acids (BAs) and serotonin) and severity of pruritus in pediatric patients with chronic cholestatic liver disease.Patients and methodsA total of 28 children suffering from pruritus due to chronic cholestatic liver disease and 29 age- and sex-matched healthy control subjects were examined. Scores obtained used the 5-D itch scale were evaluated among patients. Serum levels of BAs and serotonin were determined using enzymatic assays and high-performance liquid chromatography, respectively.ResultsPatients had higher serum BA levels and lower serotonin levels than control subjects. Serum BA levels were significantly elevated in 61% of patients. The 5-D itch scale scores were significantly higher in cholestatic individuals with normal γ-glutamyl transpeptidase levels. Neither BA nor serotonin levels correlated with the severity of the 5-Ditch scale score.ConclusionNeither BA nor serotonin levels correlated with the severity of pruritus, indicating that they may not be good laboratory markers for the intensity of itch in children with cholestasis. Our findings suggest that it is necessary to identify another potential pruritogenic mediator, most probably of a biliary origin.     

Treatment options for chronic cholestasis in infancy and childhood

Opinion statement Altered bile flow physiology leads to many complications commonly seen in patients with cholestatic liver disease, regardless of the etiology. For each individual patient, a coordinated and effective treatment strategy must address the presence and the severity spectrum of malabsorption, malnutrition, vitamin and micronutrient deficiencies, pruritus, xanthomata, ascites, and liver failure, which are attributed directly or indirectly to diminished bile flow. An aggressive approach to maximizing the nutritional status of the child is vital to ensure optimal growth and development. Protein-calorie and/or fat supplementation is best discussed early. Decreasing the percentage of dietary long-chain triglycerides, providing medium-chain triglycerides, and ensuring adequate essential fatty acid and adequate protein intake may be helpful. Fat-soluble vitamin (A, D, E, and K) levels and micronutrient levels must be carefully and serially monitored and supplemented as necessary. Because the mechanisms that mediate pruritus of cholestasis remain to be determined, the use of empirical therapies continues to be standard practice. Ursodeoxycholic acid may ameliorate pruritus. Antihistamines and rifampicin may also provide temporary relief for some children. Based on the evidence that increased central opioidergic tone is present in chronic cholestasis, the use of opiate antagonists is promising but has not been evaluated in children. Selected patients with refractory pruritus that have failed maximal medical therapy have benefited from partial external biliary diversion. Ongoing dialogue with the family regarding the indications for liver transplantation is reasonable. Optimization and adherence with the pretransplant medical management enhance the chances for a successful outcome from liver transplantation. Specific to the pediatric patient, optimizing growth, development and nutrition, minimizing discomfort and disability, and aiding the child and family in coping with the stress, social, and emotional effects of chronic liver disease remain paramount.     

A case report: nasobiliary drainage inducing remission in benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis is a rare hereditary disorder characterized by recurrent episodes of cholestasis and pruritus without anatomical obstruction. Generally, medical therapy is not effective in benign recurrent intrahepatic cholestasis. Here, we report the case of a young male patient with benign recurrent intrahepatic cholestasis who presented with cholestatic jaundice and pruritus, refractory to standard therapies. He improved on treatment with temporary endoscopic nasobiliary drainage. We propose that temporary endoscopic nasobiliary drainage should be considered in cholestatic benign recurrent intrahepatic cholestasis patients. A 36-year-old male patient admitted to our outpatient clinic with the complaint of pruritus. His anamnesis revealed that he experienced the same symptoms and signs in 2006. He was hospitalized in a hepatology clinic and was thoroughly examined. Liver biopsy was performed, and he was finally diagnosed as having benign recurrent intrahepatic cholestasis. Medical therapy options all proved to be ineffective and we were able to achieve remission in this patient only with the help of nasobiliary drainage. For this patient, we tried nasobiliary drainage in addition to the standard medical therapies. He improved on nasobiliary drainage. In conclusion, we propose that temporary endoscopic biliary drainage should be considered in cholestatic benign recurrent intrahepatic cholestasis patients. We hope that this case report contributes to the topic, since only a few nasobiliary drainage case experiences have been reported to date.     

Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid.

Cholestasis of pregnancy is associated with increased fetal morbidity and mortality and should be treated actively. The significance attached to pruritus in pregnancy is often minimal, but it is a cardinal symptom of cholestasis of pregnancy, which may have no other clinical features. Eight women with previous cholestasis of pregnancy were referred to The Liver Unit within a 12 month period for advice concerning future pregnancies. Thirteen pregnancies had been affected by cholestasis of pregnancy and 12 had been treated expectantly with resultant perinatal morbidity or mortality in 11 (one normal delivery), including; eight stillbirths, two premature deliveries with fetal distress (one died in perinatal period), and an emergency caesarean section for fetal distress. The other pregnancy was treated actively and delivery was uncomplicated. Subsequently, three of these cases with recurrent cholestasis of pregnancy were referred while pregnant. In each, cholestasis developed with severe pruritus, gross increase of serum bile acids, and deranged liver tests. Each was treated with the choleretic agent ursodeoxycholic acid, with rapid clinical improvement and resolution of deranged biochemistry. In conclusion, cholestasis of pregnancy continues to be treated expectantly despite its association with increased morbidity and mortality and evidence suggesting improved prognosis with active treatment and the potential of reducing the associated perinatal mortality. In an uncontrolled series of three patients with cholestasis of pregnancy, ursodeoxycholic acid seemed to provide safe and effective therapy.     

Unexpected clinical remission of cholestasis after rifampicin therapy in patients with normal or slightly increased levels of γ-glutamyl transpeptidase

Objective: 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.
Methods: 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 γ-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.
Results: 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.
Conclusion: Rifampicin may induce clinical remission, and perhaps prevent clinical relapses of intrahepatic cholestasis with normal or slightly increased levels of γ-glutamyl transpeptidase.