Sertraline as a first-line treatment for cholestatic pruritus

Pruritus is frequently the most debilitating symptom of cholestatic liver diseases. Moreover, existing therapies are often ineffective. Recent small, retrospective case series reports suggest that serotonin reuptake inhibitors can improve pruritus. This study was undertaken to establish the dose of sertraline and to evaluate its efficacy for cholestatic pruritus. Twenty one subjects with chronic pruritus due to liver disease (including primary biliary cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, and postnecrotic cirrhosis) initially underwent an open-label, dose escalation to determine the dose with optimal efficacy and tolerability. After a washout period, 12 of the subjects entered a randomized, double-blind, placebo-controlled trial. Participants quantified their pruritus using a 0-10 visual analog scale, and pruritus was assessed for distribution, timing, degree of disability, and physical evidence of scratching. The optimum sertraline dose (75-100 mg/day) was well tolerated. In the controlled portion of the study, itch scores improved in patients taking sertraline, but worsened in patients taking placebo (P=0.009). Changes in itch distribution, duration, direction, and physical evidence of scratching paralleled changes in the visual analog pruritus score. CONCLUSION: Sertraline seems to be an effective, well-tolerated treatment for pruritus due to chronic liver disease. These results suggest that serotonergic pathways are important in the perception of itch.     

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.     

Cholestatic liver diseases and health-related quality of life

OBJECTIVE: Symptoms associated with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) negatively affect health-related quality of life (HRQL). The aim of this study was to measure HRQL in patients with chronic cholestatic liver diseases and to determine factors associated with more severe impairment. METHODS: We conducted a cross-sectional study in which we documented patients' demographic and clinical characteristics, and measured their HRQL using the Short Form-36 and Chronic Liver Disease Questionnaire. We assessed the association of HRQL impairment with disease severity (Child's-Pugh class and Mayo PBC Risk Score) and compared patients' HRQL with those of a healthy population, and patients with congestive heart failure, chronic obstructive pulmonary disease, and diabetes. RESULTS: One hundred and four patients with PBC and PSC participated, of whom 73% were women, with an average age of 55+/-12 yr. Of these patients, 61% had cirrhosis (37% Child's A, 23% Child's B, and 2% Child's C). Patients with cholestatic liver disease showed more HRQL impairment than the healthy population and were similar to patients with other chronic conditions. Additionally, patients who experienced severe itching showed profound HRQL impairment. In patients with PBC, Physical Component Summary (PCS) scores of the SF-36 and Chronic Liver Disease Questionnaire (CLDQ) scores fell from noncirrhotic to Child's A to Child's B/C and with worsening Mayo PBC Risk Scores. No other clinicodemographic data were associated with patients' well-being. CONCLUSIONS: Patients with cholestatic liver disease (PBC and PSC) showed substantial impairment of HRQL, which is further affected by worsening disease severity. Disease-specific measures were better able to discriminate patients with varying severities.     

原发性胆汁性胆管炎相关瘙痒症的管理

原发性胆汁性胆管炎(PBC)是一种进行性肝内胆汁淤积性自身免疫性疾病,瘙痒可见于60%~70%的PBC患者,并严重影响患者的生活质量。改善PBC患者的瘙痒症状对提高患者的生活质量有着重要意义。主要总结了PBC的发病机制、PBC相关瘙痒症的治疗进展。     

Differences between Caucasian, African American, and Hispanic patients with primary biliary cirrhosis in the United States

Primary biliary cirrhosis (PBC) is an uncommon chronic cholestatic liver disease that primarily afflicts young and middle-aged Caucasian women; there are limited data on the clinical presentation and disease severity among non-Caucasian patients with this disease. The goal of this study was to examine differences in the severity of liver disease between Caucasian and non-Caucasian patients with PBC screened for enrollment in a large national multicenter clinical trial. Demographic features, symptoms, physical findings, and laboratory tests obtained during screening were examined in 535 patients with PBC with respect to ethnicity, gender, and antimitochondrial antibody (AMA) status; 73 of 535 (13.6%) were non-Caucasian (21 were African American, and 42 were Hispanic). Non-Caucasians were more likely than Caucasians to be ineligible for participation in the clinical trial (46.5% versus 25.1%, P = 0.0001), primarily because of greater disease severity. African Americans and Hispanics were also more likely to have a lower activity level, more severe pruritus, and more advanced disease. However, the mean age, male-to-female ratio, and seroprevalence of AMA positivity were similar between the 2 groups. CONCLUSION: Liver disease severity at clinical presentation is higher among non-Caucasians than Caucasians with PBC, and this cannot be explained by demographic or serologic features alone. Possible mechanisms underlying this health discrepancy are not clear, but increased awareness of PBC as a cause of chronic cholestatic liver disease is critical in evaluating non-Caucasian patients in the United States.     

Successful use of the Molecular Adsorbent Recirculating System (MARS) in a patient with primary biliary cirrhosis (PBC) and treatment refractory pruritus

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease often associated with severe pruritus. Despite maximal medical management pruritus often persists and has a detrimental effect on quality of life. For patients that are refractory to all medical treatments, more invasive approaches have been tried. Recently, a new extracorporeal hemodiafiltration method, Molecular Adsorbent Recirculating System (MARS), has been described. Based on the hypothesis that hydrophobic, protein-bound metabolites play a major role in the development of liver failure, this device uses an albumin enriched dialysate to facilitate the removal of albumin bound toxins. Aim: To assess the safety and efficacy of a single MARS treatment on the pruritus score in a patient with PBC and treatment refractory pruritus. Design/Patients: A 61-year-old female patient with biopsy proven PBC, who had been accepted on our liver transplantation waiting list because of treatment refractory pruritus, was subjected to a single MARS treatment. Results: At the end of a single 8 h MARS treatment session pruritus completely disappeared. Not unexpectedly, however, this effect was only short lived. Except for a slight hypercalcemia no adverse events were observed. Conclusion: A single MARS treatment very effectively improved pruritus. Long-term repetitive treatment, however, might be necessary to sustain its effectiveness.     

C ASE R EPORT: Oral antioxidant therapy for the treatment of primary biliary cirrhosis: A pilot study

BACKGROUND: The symptoms of the chronic cholestatic liver disease primary biliary cirrhosis (PBC), in particular fatigue and chronic pruritus, adversely affect quality of life and respond only poorly to treatment. Recent studies have suggested that oxidative stress may play a role in tissue damage in cholestatic liver disease and may contribute to symptoms, such as fatigue. We have, therefore, examined, in an open-label pilot study, the therapeutic effects of antioxidant medication on the biochemistry and symptomatology of PBC. METHODS: Patients were randomized to 3 months treatment with a compound antioxidant vitamin preparation (Bio-Antox), four tablets daily (n = 11, group 1), or the combination of Bio-Quinone Q10 (100 mg) with Bio-Antox (n = 13, group 2). Biochemical and symptomatic responses were assessed at 3 months. RESULTS: Significant improvement in both pruritus and fatigue was seen in the patients in group 2. Mean itch visual analogue score improved from 2.4 +/- 3.0 to 0.4 +/- 0.7 post therapy (P < 0.05) while mean night itch severity score improved from 2.6 +/- 1.9 to 1.3 +/- 0.7 (P < 0.05). Nine of 13 of these patients reported less fatigue, while 10/13 showed an improvement in at least one domain of their Fisk Fatigue Severity Score. No significant improvement in itch and only limited improvement in fatigue were seen in the patients in group 1. No change in biochemical parameters was seen in either group. CONCLUSIONS: Antioxidant therapy, as a combination of Bio-Antox and Bio-Quinone Q10, may improve the pruritus and fatigue of PBC. This combination of therapy should be investigated further in a double-blind, placebo-controlled trial.     

Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome

AIM: To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC).METHODS: Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 ± 11.2 vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.     

Role of intravenous naloxone in severe pruritus of acute cholestasis

Pruritus is a well-known manifestation of various cholestatic disorders. Increased opioidergic tone is one of the mechanisms for this. This prospective, uncontrolled study was done to determine the efficacy of intravenous naloxone in pruritus of acute cholestasis. Twenty-two patients with severe pruritus (based on visual analogue scale [VAS] score of 0–100 and associated symptoms) were treated with intravenous naloxone (0.4 mg every 8 hours) for at least 48 hours. Viral hepatitis E was found to be the most common etiology for cholestatic pruritus (n=12). Eighteen patients (81.8%) patients had significant reduction in VAS after 48 hours of starting naloxone; these patients also showed reduction in alkaline phosphatase and gamma glutamyl transpeptidase. There was no side-effect or ‘breakthrough’ phenomenon noted in any patient over next 6 weeks. Naloxone is safe and efficacious in symptomatic improvement in cholestatic pruritus.     

Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant

The clinical and pathological findings of four females with primary biliary cirrhosis (PBC) with an unusual and hitherto not well recognised course are reported. Patients suffered severe pruritus and weight loss with progressive icteric cholestasis which did not respond to such treatments as ursodeoxycholic acid and immunosuppressives. In all cases liver histology revealed marked bile duct loss without however significant fibrosis or cirrhosis. Further diagnostic studies and repeat biopsies confirmed the absence of liver cirrhosis as well as other potential causes of hyperbilirubinaemia. Comparison of the fibrosis-ductopenia relationship for our cases with that for a group of 101 non-cirrhotic PBC patients indicated that in the former the severity of bile duct loss relative to the amount of fibrosis was significantly higher. The proportion of portal triads containing an interlobular bile duct was 3%, 4%, 6%, and 10% compared with 45% (median; range 8.3--100%) for controls (p<0.001). Three patients received a liver transplant 6--7 years after the first manifestation of PBC because of progressive cholestasis, refractory pruritus, and weight loss, while the fourth patient is considering this option. In one case cirrhosis had developed at the time of transplantation while the others still had non-cirrhotic disease. These cases suggest that cholestatic jaundice in non-cirrhotic PBC may be secondary to extensive "premature" or accelerated intrahepatic bile duct loss. Although the extent of fibrosis may be limited initially, progression to cirrhosis appears to be inevitable in the long run. Despite intact protein synthesis and absence of cirrhotic complications, liver transplantation in the pre-cirrhotic stage for preventing malnutrition and to improve quality of life should be considered for these patients.     

Oxygen-derived free radical production by peripheral blood neutrophils in chronic cholestatic liver diseases.

BACKGROUND/AIMS: Patients with chronic cholestasis, particularly those with associated cirrhosis, are susceptible to infectious complications. From animal models it has been postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMNL) function by impeding chemotaxis, phagocytosis and superoxide release, which are necessary for an adequate immune response. The aim of this study was to evaluate neutrophil activity in the production of oxygen-derived free radicals in chronic cholestatic liver diseases. METHODOLOGY: The following groups were included in the study: 27 primary biliary cirrhosis (PBC) patients, 12 primary sclerosing cholangitis (PSC) patients, and 3 control groups (29 healthy subjects, 19 patients with HCV-related cirrhosis and 23 ulcerative colitis (UC) patients). Peripheral neutrophils were isolated from heparinized blood samples and PMNL activity was measured by free radical production, using a chemiluminometer, after stimulation with fMLP, PMA and Zymosan. The effect of liver disease severity and degree of cholestasis on PMNL function was also evaluated. RESULTS: Both PBC and PSC patients exhibited a normal PMNL activity compared to healthy subjects after the three stimuli used. In PBC patients only (but not in PSC patients), the histological stage of the disease seems to positively influence ROS production. Stage IV PBC patients showed a significantly higher PMNL activity compared to HCV-related cirrhotic patients. PSC patients failed to show any difference according to the association with UC. CONCLUSIONS: The increased susceptibility to bacterial infections in patients with chronic cholestatic liver disease is not related to an impaired PMNL activity. However, our findings may support the influence of biohumoral factors (cytokines?) on PMNL activation.     

When is liver biopsy needed in the diagnosis of primary biliary cirrhosis?

BACKGROUND & AIMS: Liver biopsy has been largely replaced by less invasive measurements applied to mathematical models in defining the prognosis of patients with primary biliary cirrhosis (PBC). The need for liver biopsy in the diagnosis of patients with positive antimitochondrial antibodies (AMAs) in the setting of biochemical cholestasis remains uncertain. This study was undertaken to determine which variables indicate the need for liver biopsy in patients with positive AMA and suspected PBC. METHODS: A total of 3198 patients that were tested for AMA in 1999 and 2000 were identified. Of these, 198 (6.2%) were AMA positive. Forty-two patients were excluded because of unavailable laboratory data or liver biopsy specimens. Data on the remaining 156 patients were analyzed to determine which variables among patients with positive AMA with and without a histopathologic diagnosis of PBC indicate the need for liver biopsy. RESULTS: In 131 of 156 (84.6%) patients, a diagnosis of PBC was established by liver biopsy. The histological diagnosis of PBC was associated with a cholestatic biochemical profile (alkaline phosphatase [AP] >1.5 times the upper limits of normal [ULN] and aspartate aminotransferase [AST] <5 times ULN) in 112 of 131 (85.5%) patients. The combination of AP >1.5 times the ULN and AST <5 times the ULN yielded a 98.2% positive predictive value of PBC diagnosis on liver biopsy in AMA-positive subjects. These results were corroborated by cross-validation in an independent set of patients. CONCLUSIONS: In patients with positive AMA, a cholestatic biochemical profile (AP >1.5 times the ULN), and absence of markedly elevated AST (<5 times the ULN), liver biopsy is rarely required to establish the diagnosis of PBC. Liver biopsy would be beneficial to establish the diagnosis of PBC in only a minority of AMA-positive patients with AP <1.5 times the ULN or AST >5 times the ULN.     

Latest and Emerging Therapies for Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are the two most common causes of chronic cholestatic liver disease in adults. In PBC, therapy with ursodeoxycholic acid (UDCA) is safe and has been associated with tangible biochemical, histologic, and survival benefits. However, a need for different or adjuvant therapies remains for specific subsets of PBC patients, including those who do not respond to UDCA and those who have advanced histologic disease at presentation. Similarly, beneficial therapies for disease-related symptoms that do not typically respond to UDCA (eg, fatigue and pruritus) are still needed. In contrast to PBC, no medical therapy of proven benefit has been identified for patients with PSC. In PBC and PSC, adequate management of complications of chronic cholestasis is important. For both diseases, liver transplantation is the only curative option.     

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.     

Lysophosphatidic acid and atotaxin in patients with cholestasis and pruritus: Fine biology, anticipated discernme

Background &; aims. Pruritus is a common and disabling symptom in cholestatic disorders. However, its causes remain unknown. We hypothesized that potential pruritogens accumulate in the circulation of cholestatic patients and activate sensory neurons. Methods. Cytosolic free calcium ([Ca(2+)] (i)) was measured in neuronal cell lines by ratiometric fluorometry upon exposure to serum samples from pruritic patients with intrahepatic cholestasis of pregnancy (ICP), primary biliary cirrhosis (PBC), other cholestatic disorders, and pregnant, healthy, and nonpruritic disease controls. Putative [Ca(2+)] (i)-inducing factors in pruritic serum were explored by analytical techniques, including quantification by high-performance liquid chromatography/mass spectroscopy. In mice, scratch activity after intradermal pruritogen injection was quantified using a magnetic device. Results. Transient increases in neuronal [Ca(2+)] (i) induced by pruritic PBC and ICP sera were higher than corresponding controls. Lysophosphatidic acid (LPA) could be identified as a major [Ca(2+)] (i) agonist in pruritic sera, and LPA concentrations were increased in cholestatic patients with pruritus. LPA injected intradermally into mice induced scratch responses. Autotaxin, the serum enzyme converting lysophosphatidylcholine into LPA, was markedly increased in patients with ICP vs. pregnant controls (P < 0.0001) and cholestatic patients with vs. without pruritus (P < 0.0001). Autotaxin activity correlated with intensity of pruritus (P < 0.0001), which was not the case for serum bile salts, histamine, tryptase, substance P, or mu-opioids. In patients with PBC who underwent temporary nasobiliary drainage, both itch intensity and autotaxin activity markedly decreased during drainage and returned to preexistent levels after drain removal. Conclusions. We suggest that LPA and autotaxin play a critical role in cholesta-tic pruritus and may serve as potential targets for future therapeutic interventions.     

Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis

There is evidence to suggest that rifampicin is an effective second line therapy for controlling pruritus in patients with chronic cholestatic liver disease. It is most widely used as an antipruritic agent in the autoimmune cholestatic liver disease, primary biliary cirrhosis (PBC). Rifampicin has been reported as causing hepatitis in patients being treated for tuberculosis. Most reports of this have been confounded however by the concurrent use of other hepatotoxic antitubercular therapy. Here we report a single centre experience of the use of rifampicin in PBC, and describe three cases of significant hepatitis associated with rifampicin therapy. Two of these patients had significant impairment of liver synthetic function (necessitating liver transplantation in one case). These are the first reports of impaired hepatic synthetic function due to rifampicin monotherapy. Rifampicin caused significant hepatitis in 7.3% (95% confidence interval 2.5-19.4%) of patients treated for cholestatic liver disease in our centre.     

Primary biliary cirrhosis--presentation and diagnosis

Primary biliary cirrhosis is predominantly seen in middle-aged women. Typical symptoms are fatigue, pruritus, and abdominal pain. Jaundice develops in the endstage disease. At presentation, about 40% of the patients are asymptomatic, but 30% to 50% already have hepatomegaly, and 15% present with splenomegaly. Even patients with fully developed liver cirrhosis may be free of symptoms. Abnormal physical signs and advanced histological stage are more frequent in symptomatic than in asymptomatic patients. Fatigue, pruritus, and Sj?gren's syndrome are more common in women than men, but other signs and symptoms do not differ in the two sexes. PBC is associated with a large variety of other diseases, like arthropathy, CREST syndrome, autoimmune thyroiditis, and so on, which in addition will or will not produce symptoms. Hepatocellular carcinoma is a rare complication in women, but more frequent in men. Diagnosis can be established by the triad antimitochondrial antibodies (AMA), cholestatic indices, and liver histology, diagnostic or compatible with PBC. When AMA are not detected, then antinuclear antibodies (autoantibodies against gp.210 and others) can be detected in 50% of AMA-negative patients. AMA titers do not correlate with the course of the disease nor histological progression. After liver transplantation, AMA recur in nearly 100%. The liver enzyme pattern in PBC patients is cholestatic: alkaline phosphatase and gammaglutamyltransferase increase to 10 or more times the upper limit of normal. The amount of enzymes does not correlate with disease progression or stage of the disease. The only prognostic factor in PBC is serum bilirubin. AMA-negative patients account for about 10% to 15%. Routine biochemical tests are not different from AMA-positive patients, but usually higher ANA, SMA, and IgG concentrations are detected. Histologically, it is PBC. The overlap-syndrome, autoimmune hepatitis-PBC presents with the histological features of autoimmune hepatitis and PBC, with AMA, ANA, or SMA. Imaging procedures are not helpful for the diagnosis of PBC, except for liver histology. Histologically, four different stages can be assessed, ranging from florid bile duct lesions, ductular proliferation, and fibrosis to liver cirrhosis. Liver histology is of interest for the assessment of the diagnosis and for staging of the disease.     

Natural history of pruritus in primary biliary cirrhosis.

The natural history of pruritus in primary biliary cirrhosis (PBC) remains poorly defined. The aim of this investigation was to evaluate outcomes of pruritus in clinical trials for ursodeoxycholic acid (UDCA). In a UDCA-placebo trial begun in 1988 (n = 180), a 55% prevalence rate for pruritus was observed. Serum alkaline phosphatase level and Mayo risk score were independent risk factors for pruritus (P < 0.0001). Among placebo-treated patients (n = 91), the annual risks for development or improvement/resolution of pruritus were 27% and 23%, respectively. For UDCA-treated patients (n = 89), a trend toward improvement in pruritus was observed after 1 year compared to placebo (30% vs. 23%, P = 0.08) but not at 2 or 3 years. In a 3-dose UDCA trial begun in 1995 (n = 155), the overall prevalence of pruritus was significantly lower at 37% when compared to UDCA-placebo participants (P < 0.001). Baseline serum alkaline phosphatase level and Mayo risk score were again independent risk factors for pruritus (P < 0.0001). Among 13 (3.9%) patients with refractory pruritus, symptom resolution (n = 5) or improvement (n = 8) was associated with the use of oral rifampin (300 or 600 mg daily). Two patients treated with rifampin developed biochemical evidence for hepatotoxicity necessitating drug withdrawal. Although less prevalent among recently diagnosed individuals, more than one third of PBC patients develop pruritus. No significant risk reduction in developing pruritus with UDCA therapy was observed compared to placebo-treated patients. The long-term administration of rifampin for refractory pruritus is associated with occasional hepatotoxicity.     

Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease

Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients had previously been extensively treated with standard therapies for ICRP including: diphenhydramine, chlorpheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations. All patients were started on 5 mg of delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4-6 hrs in all three patients suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus.     

Effect of oral naltrexone on pruritus in cholestatic patients

AIM:To determine the efficacy and potential complica-tions of oral naltrexone used in the treatment of pruritusin cholestatic patients and to compare them with otherstudies.METHODS:Thirty-four enrolled cholestatic patientscomplaining of pruritus were studied.In the initial phase,pruritus scores during day and night were evaluated.Sub-sequently,patients were given a placebo for one weekfollowed by naltrexone for one week.In each therapeuticcourse(placebo or naltrexone)day and night pruritusscores were distinguished by a visual analogue scale(VAS)system and recorded in patients'questionnaires.RESULTS:Both naltrexone and placebo decreased VASscores significantly.Naltrexone was more effective thanplacebo in decreasing VAS scores.Both day and nightscores of pruritus decreased by half of the value priorto therapy in thirteen patients(38%).Daytime pruritusimproved completely in two patients(5.9%),but no im-provement in the nighttime values was observed in anypatient.Sixteen patients(47%)suffered from naltrexonecomplications,eleven(32%)of them were related to itswithdrawal.Complications were often mild.In the caseof withdrawal,the complication was transient(withinthe first 24-28 h of therapy)and self-limited.We had tocease the drug in two cases(5.9%)because of severewithdrawal symptoms. CONCLUSION:Naltrexone can be used in the treatmentof pruritus in cholestatic patients and is a safe drugshowing few,mild and self-limited complications.