- Email: [email protected]
671 EFFICACY OF NASOBILIARY DRAINAGE FOR REFRACTORY CHOLESTATIC PRURITUS
S246
Poster Session − Friday, April 24
Results: The PCr/ATP ratio was significantly reduced in PBC patients compared to controls (1.90±0.1 v1.64±0.23, p = 0.008). A PCr/ATP ratio of <1.6 (previously identified as indicating significant cardiac metabolic dysfunction associated with increased mortality risk) was seen in 6/15 (40%) PBC patients but absent from controls (p < 0.05). High resolution MR imaging showed no differences between PBC patients and controls with regard to any parameter of cardiac structure or function. Conclusions: Significant cardiac muscle bioenergetic abnormality is common in PBC patients and occurs, in the apparent absence of structural cardiac disease, at levels previously associated with increased cardiac mortality from sudden cardiac death. This may be a manifestation of acquired mitochondrial dysfunction. 670 REGULATION OF CEREBRAL BLOOD FLOW IS SIGNIFICANTLY IMPAIRED IN PRIMARY BILIARY CIRRHOSIS J. Frith, D.E.J. Jones, J. Newton. Biomedical Research Centre in Ageing − Liver Theme, Newcastle University, Newcastle upon Tyne, UK E-mail: [email protected] Background and Aims: Recent studies in Primary Biliary Cirrhosis (PBC) have confirmed that cognitive symptoms are frequently seen, and that actual cognitive impairment associates with structural brain lesions on MRI, the density of which correlates with autonomic dysfunction [1]. Regulation of cerebral blood flow is vital to protect the brain from the fluctuations in blood pressure (BP) seen in autonomic dysfunction which can manifest as episodes of sudden hypotension potentially leading to cerebral ischemia. In this study we set out to address the hypothesis that PBC patients have impaired cerebral autoregulation which may predispose to cerebral ischemia and potentially cognitive dysfunction, by examining cerebral autoregulation in response to hypotension induced during a valsalva manoeuvre (VM). Methods: 10 patients with early stage (non-cirrhotic) PBC and 10 age- and sex-matched controls underwent doppler sonography of blood flow in the middle cerebral artery with simultaneous beat to beat BP monitoring (Taskforce;CNSystems). Participants performed VM to assess cerebral blood flow responses to changes in systemic BP. Three indices were calculated to assess appropriate response [Autoregulatory Index for Valsalva phase 2 (AI2) and Valsalva phase 4 (AI4), and the Autoregulatory Slope Index (ASI)]. For AI2 and AI4 values >1 are deemed to be normal [2]. Results: The mean age of participants was 65±7 years, all had normal carotid blood flow, and each performed an effective VM. The AI2 and ASI were significantly worse in the PBC group compared to controls (0.4±2.1 vs. 3.4±2.2, P = 0.0064 & −2±9 vs. 22±14, P < 0.0001 respectively). All control subjects (n = 10) had appropriate levels of blood flow regulation using AI2 and AI4 compared to only 20% and 40% of PBC subjects respectively. Conclusions: Cerebral blood flow regulation is significantly impaired in PBC, and dysregulation is highly prevalent in our cohort. This study suggests that PBC patients may be at risk from the sequelae of fluctuations in BP which may lead to subclinical cerebral ischemia during postural hypotension. This is a potential reversible mechanism to explain the recently recognized cognitive impairment seen in those with PBC. Further longitudinal studies are needed. References [1] Newton et al., Hepatology 2008;48:541−9. [2] Tiecks et al., Stroke 1995;26:1386−92.
671 EFFICACY OF NASOBILIARY DRAINAGE FOR REFRACTORY CHOLESTATIC PRURITUS E.M.M. Kuiper, R.A. de Man, H.R. van Buuren. Hepatology and Gastroenterology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands E-mail: [email protected] Background and Aims: Nasobiliary drainage (NBD) has been reported to be effective in pruritus secondary to benign recurrent intrahepatic
cholestasis (BRIC) (Stapelbroek et al. Hepatology 2006;43:51−3). The aim of this study was to further explore the feasibility and efficacy of NBD in severe refractory pruritus associated with cholestatic conditions of any etiology. Methods: We selected patients with severe cholestatic pruritus who did not respond to medical treatment including cholestyramine, rifampicin and naltrexon. A nasobiliary drain was inserted during ERCP for 7 days. The effect of drainage was evaluated using visual analogue scales (VAS) for pruritus and fatigue and by laboratory studies including serum bile acids, bilirubin, ALP, AST and ALT before, during and after NBD. Results: 7 consecutive patients (5 females, 2 males; mean age 40 yrs) were included. Causes of cholestatic pruritus were PBC (n = 2), PSC (n = 1) and BRIC (n = 4, based on clinical features, although negative for ATP8B1/ABCB11 mutations). All patients experienced marked improvement of pruritus within 7 days. The mean decrease of the pruritus VAS score was 64% (SD±30). Laboratory tests all improved markedly (see figure). Patients were followed for a mean period of 15 (SD±10) months. Four patients remained free of pruritus during follow-up. Pruritus recurred in 3/7 (43%) patients immediately following removal of the drain (PSC; n = 1), after 1 week (PBC; n = 1) and after 12 months (BRIC; n = 1). 2/7 (29%) patients developed mild post-ERCP pancreatitis. Conclusions: Nasobiliary drainage is an invasive procedure associated with potential complications, but may result in long-term relief of severe, refractory cholestatic pruritus. Our results suggest that beneficial effects of NBD can not only be obtained in BRIC but also in other cholestatic conditions and confirm older observations of the utility of surgical biliary drainage to treat cholestatic pruritus.
Figure: Effect NBD expressed as mean values before and after NBD.
672 CHAZOUILLERES CRITERIA ARE SUPERIOR TO THE REVISED AND SIMPLIFIED AUTOIMMUNE HEPATITIS SCORES FOR DIAGNOSING THE OVERLAP SYNDROME OF PRIMARY BILIARY CIRRHOSIS AND AUTOIMMUNE HEPATITIS E.M.M. Kuiper1 , P.E. Zondervan2 , H.R. van Buuren1 . 1 Hepatology and Gastroenterology, 2 Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands E-mail: [email protected] Background and Aims: Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) differ in clinical, biochemical, serological and histological features. However, a subgroup of patients has an Overlap Syndrome (OS), with features of both diseases. At present, consensus is lacking as to the precise diagnostic criteria for such an OS. We aimed to evaluate the value and accuracy of relevant scoring systems. Methods: Review of all patients with a clinical diagnosis of AIH, PBC or OS diagnosed after January 1990. Available liver biopsies were revised. Patients were classified according to criteria for OS proposed by Chazouilleres (CC) (Hepatology 1998;28:296–301), and according to the revised (before treatment) (rAIH) and recently introduced simplified AIHscores (sAIH).
Poster Session − Friday, April 24
Results: The PCr/ATP ratio was significantly reduced in PBC patients compared to controls (1.90±0.1 v1.64±0.23, p = 0.008). A PCr/ATP ratio of <1.6 (previously identified as indicating significant cardiac metabolic dysfunction associated with increased mortality risk) was seen in 6/15 (40%) PBC patients but absent from controls (p < 0.05). High resolution MR imaging showed no differences between PBC patients and controls with regard to any parameter of cardiac structure or function. Conclusions: Significant cardiac muscle bioenergetic abnormality is common in PBC patients and occurs, in the apparent absence of structural cardiac disease, at levels previously associated with increased cardiac mortality from sudden cardiac death. This may be a manifestation of acquired mitochondrial dysfunction. 670 REGULATION OF CEREBRAL BLOOD FLOW IS SIGNIFICANTLY IMPAIRED IN PRIMARY BILIARY CIRRHOSIS J. Frith, D.E.J. Jones, J. Newton. Biomedical Research Centre in Ageing − Liver Theme, Newcastle University, Newcastle upon Tyne, UK E-mail: [email protected] Background and Aims: Recent studies in Primary Biliary Cirrhosis (PBC) have confirmed that cognitive symptoms are frequently seen, and that actual cognitive impairment associates with structural brain lesions on MRI, the density of which correlates with autonomic dysfunction [1]. Regulation of cerebral blood flow is vital to protect the brain from the fluctuations in blood pressure (BP) seen in autonomic dysfunction which can manifest as episodes of sudden hypotension potentially leading to cerebral ischemia. In this study we set out to address the hypothesis that PBC patients have impaired cerebral autoregulation which may predispose to cerebral ischemia and potentially cognitive dysfunction, by examining cerebral autoregulation in response to hypotension induced during a valsalva manoeuvre (VM). Methods: 10 patients with early stage (non-cirrhotic) PBC and 10 age- and sex-matched controls underwent doppler sonography of blood flow in the middle cerebral artery with simultaneous beat to beat BP monitoring (Taskforce;CNSystems). Participants performed VM to assess cerebral blood flow responses to changes in systemic BP. Three indices were calculated to assess appropriate response [Autoregulatory Index for Valsalva phase 2 (AI2) and Valsalva phase 4 (AI4), and the Autoregulatory Slope Index (ASI)]. For AI2 and AI4 values >1 are deemed to be normal [2]. Results: The mean age of participants was 65±7 years, all had normal carotid blood flow, and each performed an effective VM. The AI2 and ASI were significantly worse in the PBC group compared to controls (0.4±2.1 vs. 3.4±2.2, P = 0.0064 & −2±9 vs. 22±14, P < 0.0001 respectively). All control subjects (n = 10) had appropriate levels of blood flow regulation using AI2 and AI4 compared to only 20% and 40% of PBC subjects respectively. Conclusions: Cerebral blood flow regulation is significantly impaired in PBC, and dysregulation is highly prevalent in our cohort. This study suggests that PBC patients may be at risk from the sequelae of fluctuations in BP which may lead to subclinical cerebral ischemia during postural hypotension. This is a potential reversible mechanism to explain the recently recognized cognitive impairment seen in those with PBC. Further longitudinal studies are needed. References [1] Newton et al., Hepatology 2008;48:541−9. [2] Tiecks et al., Stroke 1995;26:1386−92.
671 EFFICACY OF NASOBILIARY DRAINAGE FOR REFRACTORY CHOLESTATIC PRURITUS E.M.M. Kuiper, R.A. de Man, H.R. van Buuren. Hepatology and Gastroenterology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands E-mail: [email protected] Background and Aims: Nasobiliary drainage (NBD) has been reported to be effective in pruritus secondary to benign recurrent intrahepatic
cholestasis (BRIC) (Stapelbroek et al. Hepatology 2006;43:51−3). The aim of this study was to further explore the feasibility and efficacy of NBD in severe refractory pruritus associated with cholestatic conditions of any etiology. Methods: We selected patients with severe cholestatic pruritus who did not respond to medical treatment including cholestyramine, rifampicin and naltrexon. A nasobiliary drain was inserted during ERCP for 7 days. The effect of drainage was evaluated using visual analogue scales (VAS) for pruritus and fatigue and by laboratory studies including serum bile acids, bilirubin, ALP, AST and ALT before, during and after NBD. Results: 7 consecutive patients (5 females, 2 males; mean age 40 yrs) were included. Causes of cholestatic pruritus were PBC (n = 2), PSC (n = 1) and BRIC (n = 4, based on clinical features, although negative for ATP8B1/ABCB11 mutations). All patients experienced marked improvement of pruritus within 7 days. The mean decrease of the pruritus VAS score was 64% (SD±30). Laboratory tests all improved markedly (see figure). Patients were followed for a mean period of 15 (SD±10) months. Four patients remained free of pruritus during follow-up. Pruritus recurred in 3/7 (43%) patients immediately following removal of the drain (PSC; n = 1), after 1 week (PBC; n = 1) and after 12 months (BRIC; n = 1). 2/7 (29%) patients developed mild post-ERCP pancreatitis. Conclusions: Nasobiliary drainage is an invasive procedure associated with potential complications, but may result in long-term relief of severe, refractory cholestatic pruritus. Our results suggest that beneficial effects of NBD can not only be obtained in BRIC but also in other cholestatic conditions and confirm older observations of the utility of surgical biliary drainage to treat cholestatic pruritus.
Figure: Effect NBD expressed as mean values before and after NBD.
672 CHAZOUILLERES CRITERIA ARE SUPERIOR TO THE REVISED AND SIMPLIFIED AUTOIMMUNE HEPATITIS SCORES FOR DIAGNOSING THE OVERLAP SYNDROME OF PRIMARY BILIARY CIRRHOSIS AND AUTOIMMUNE HEPATITIS E.M.M. Kuiper1 , P.E. Zondervan2 , H.R. van Buuren1 . 1 Hepatology and Gastroenterology, 2 Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands E-mail: [email protected] Background and Aims: Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) differ in clinical, biochemical, serological and histological features. However, a subgroup of patients has an Overlap Syndrome (OS), with features of both diseases. At present, consensus is lacking as to the precise diagnostic criteria for such an OS. We aimed to evaluate the value and accuracy of relevant scoring systems. Methods: Review of all patients with a clinical diagnosis of AIH, PBC or OS diagnosed after January 1990. Available liver biopsies were revised. Patients were classified according to criteria for OS proposed by Chazouilleres (CC) (Hepatology 1998;28:296–301), and according to the revised (before treatment) (rAIH) and recently introduced simplified AIHscores (sAIH).