Billiary Cirrhosis Research Articles

Fast estimation for generalised multivariate joint models using an approximate EM algorithm

Joint models for longitudinal and survival data have become an established tool for optimally handling scenarios when both types of data co-exist. Multivariate extensions to the classic univariate joint model have started to emerge but are typically restricted to the Gaussian case, deployed in a Bayesian framework or focused on dimension reduction. An approximate EM algorithm is utilised which circumvents the oft-lamented curse of dimensionality and offers a likelihood-based implementation which ought to appeal to clinicians and practitioners alike. The proposed method is validated in a pair of simulation studies, which demonstrate both its accuracy in parameter estimation and efficiency in terms of computational cost. Its clinical use is demonstrated via an application to primary billiary cirrhosis data. The proposed methodology for estimation of these joint models is available in R package gmvjoint.

Comparative study of prevalence of hypothyroidism in cirrhotic patients and normal individuals

Background: Alcoholic cirrhosis has worse prognosis than primary billiary cirrhosis and cirrhosis due to hepatitis. The risk of death due to all cause is increased 12-fold with cirrhosis. Alcoholic liver cirrhosis develops between 10-20% of individuals who drink heavily for a decade or more. Chronic hepatitis B is probably the most common cause of cirrhosis worldwide. The aim and objective of this study was to compare the prevalence of hypothyroidism between cirrhotic patients and normal healthy individuals.Methods: The present study constitutes of 50 patients with cirrhosis of liver who met our inclusion criteria. They were selected from the patients admitted in medical wards and gastroenterology ward of RNT medical college, Udaipur.Results: Majority of patients were of serum albumin level class III about 67%. Increased TSH level as compare to level of serum albumin in cirrhotic patients. When serum albumin level decreases then percent of TSH level increases. Majority of patients were from serum bilirubin class III (71%). Majority were from serum bilirubin class III about 70%.Conclusions: All cirrhotic patients should undergo for evaluation of endocrinological evaluation as these patients are associated with development of hypothyroidism. After diagnosis the treatment of endocrinological disorder especially hypothyroidism may increase survival.

P1552 Dobutamine stress echocardiography as a screening tool for coronary artery disease detection in patients with end-stage liver disease awaiting transplantation

Abstract Indroduction The prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) is unknown. However, patients with CAD and ESLD are at increased perioperative risk during liver transplantation. Currently there is no standard protocol for CAD screening in patients with ESLD awaiting orthotopic liver transplantation. We present preliminary data of our experience with dobutamine stress echocardiography in those patients. Methods Fifty patients (26 males, mean age of 59 years) with end-stage liver disease awaiting transplantation and no history of CAD underwent dobutamine stress echo. The etiology of their hepatic disease was hepatitis B (6 patients), hepatitis C (6 patients), primary billiary cirrhosis (10 patients), sclerosing cholangitis (8 patients), alcoholic hepatitis (10 patients) and polycystic disease (2 patients), while 8 patients had end-stage liver disease of unknown etiology. Twenty-six patients had risk factors for CAD. Eighteen patients had one risk factor and only 8 patients had 2 risk CAD factors. All patients received dobutamine infusion (at escalating doses of 5, 10, 20, 30 and 40 μgr/kg/min), targeting a 85% or more of their age-predicted maximum heart rate. Atropine was administered in 6 patients. Results All 50 patients had normal inotropic response of left ventricle, without evidence of ischemia (100% studies were negative for ischaemia). No patient had major intolerance to dobutamine. Eight patients experienced hypotension responded to infusion of normal saline. One patient developed paroxysmal supraventricular tachycardia, which was treated with intravenous bolus of adenosine. No patient had cardiovascular events during a follow-up ranging from 1 to 18 months. Twelve patients underwent liver transplantation without any periprocedural cardiovascular events. Conclusions Dobutamine stress echocardiography is a safe and reliable method for CAD screening in the labile patients with ESLD who are candidates for orthotopic liver transplantation. It seems that the prevalence of significant CAD in this high-risk population is low.

Determining the frequency and severity of malnutrition and correlating it with the severity of liver cirrhosis

Malnutrition is a significant problem in cirrhosis of the liver worldwide. Inadequate data is available on the nutritional status of Pakistani patients. This study aimed to determine the frequency and severity of malnutrition in patients having cirrhosis of the liver and to compare the degree of malnutrition with the severity of liver disease. Two hundred ninety-eight patients with liver cirrhosis were included in the study. Nutritional status was assessed using the Royal Free Hospital Global Assessment scheme for cirrhotics. The patients were categorized into well-nourished, and mild to moderately and severely malnourished. Various degrees of malnutrition were compared with severity of disease according to Child-Pugh staging. In the 298 patients with liver cirrhosis, hepatitis C (54,36%) and B (35,90%) were the commonest aetiologies, followed by autoimmune hepatitis (3,35%), primary billiary cirrhosis (2,34%), Wilson's disease (1,34%), haemochromatosis (1,0%), cryptogenic cirrhosis (1,0%), and alcohol being the rare cause (0,67%). 14,42% patients were well-nourished, (54,02%) were mildto moderately malnourished and (31,54%) were severely malnourished. Malnutrition is more frequent in virus-related cirrhosis, and the degree of malnutrition increases with increasing clinical severity as assessed by Child- Pugh stages with statistically significant p-value of 0.001. Moderate to severe malnutrition among diverse aetiologies of cirrhosis is quite common in Pakistan. The degree of malnutrition increases with increasing clinical severity of cirrhosis of liver.

SAT0156 Cryoglobulinemic Vasculitis: Study of 34 Patients from a Single Center According to the New Nomenclature of Vasculitis Of Chapel Hill 2012

BackgroundCryoglobulinemic vasculitis (Vcrio) is characterized by the presence of circulating cryoglobulins usually affecting small blood vessel. The Nomenclature of Chapel Hill 1993 (A&R 1994;37:187) considered all VCrio generically. However, VCrio...

Creation of a Solid Organ Transplant Program in an Underdeveloped Country: Mexico's General Hospital Transplantation Program

BackgroundWith a population of >112 million persons, all Mexicans are entitled to receive medical care by the state and more than half have limited access to healthcare. From January 1985 to March 2009, 40 renal transplants were performed from living donors with a high percentage of complications. In April 2009, a new Solid Organ Transplantation Program was started; herein, we present this enterprise to the international community and briefly present a perspective on the Mexican transplant situation. Materials and MethodsWe performed a retrospective chart review of kidney and liver transplant recipients from April 2009 to November 2011, including demographic features, immunosuppression, complications as well as initial and 1 month function. ResultsWe performed 68 kidney (59 living and 9 deceased donors) and 5 liver transplants (cadaveric donors). The kidney transplant recipients were 73.5% males and showed an overall mean age of 29.77 years (range, 18–60). The donor mean age was 34.08 years. Mean recipient creatinine pretransplant was 13.32 mg/dL, while at day 5 it was 2.33 and at month one, 1.32 mg/dL. Five grafts were lost (7.3%): 4 due to death with a functioning graft and 1 due to acute pyelonephritis. Five patients experienced delayed graft function Basiliximab induction was required in all but one who received thymoglobulin owing to a high panel reactive antibody. Maintenance therapy included a calcineurin inhibitor, mycophenolate mofetil (MMF), and prednisone. Liver transplant recipients were 83.6% women. The etiologies were alcoholic cirrhosis (n = 2), primary billiary cirrhosis (n = 1) and hepatitis C virus infection (n = 2). Complications included: reperfusion syndrome (n = 1), convulsive crisis (medication; n = 1), acute respiratory distress syndrome (n = 1), and death (n = 1). Their Model for End-Stage Liver Disease scopes were 10–21. After basiliximab induction, they had maintenance therapy with tacrolimus, MMF, and steroids. The donor mean age was 26.2 years. All survivors show normal liver function tests currently. ConclusionsFrom 1985 to 2009, 40 kidney transplants were performed, with multiple complications including donor deaths. Our current results were comparable to international standards, with <15% complication rate.

Sa1313 Rotating Antibiotics for the Treatment of Recurrent Bacterial Cholangitis in Primary Billiary Cirrhosis Patients Who Have Had Orthotopic Liver Transplantation With Roux-en-Y Choledochojejunostomy

Sa1313 Rotating Antibiotics for the Treatment of Recurrent Bacterial Cholangitis in Primary Billiary Cirrhosis Patients Who Have Had Orthotopic Liver Transplantation With Roux-en-Y Choledochojejunostomy

Investigating the relationship between anti-gp210 antibody and clinical basic profile of primary billiary cirrhosis

Investigating the relationship between anti-gp210 antibody and clinical basic profile of primary billiary cirrhosis

Interaction Trees with Censored Survival Data

We propose an interaction tree (IT) procedure to optimize the subgroup analysis in comparative studies that involve censored survival times. The proposed method recursively partitions the data into two subsets that show the greatest interaction with the treatment, which results in a number of objectively defined subgroups: in some of them the treatment effect is prominent while in others the treatment may have a negligible or even negative effect. The resultant tree structure can be used to explore the overall interaction between treatment and other covariates and help identify and describe possible target populations on which an experimental treatment demonstrates desired efficacy. We follow the standard CART (Breiman, et al., 1984) methodology to develop the interaction tree structure. Variable importance information is extracted via random forests of interaction trees. Both simulated experiments and an analysis of the primary billiary cirrhosis (PBC) data are provided for evaluation and illustration of the proposed procedure.

BILLIARY CIRRHOSIS: CONFORMATIONAL EFFECTS AND CONSEQUENCES OF THE OXIDATION OF HEPATIC SERPINS

Introduction: Billiary cirrhosis is associated with the production of exacerbated levels of reactive oxygen species (ROS) that might alter the normal folding of serpins, as we previously showed in vitro. Methods: The aims of our work were to evaluate in vivo the conformational effects of high levels of circulating ROS on two hepatic serpins, antithrombin (AT) and alpha1-antitrypsin (alpha1-AT) in a rat model of billiary cirrhosis. Billiary cirrhosis was established in Sprague Dawley rats by means of bile duct ligation and maintained during 7, 14 or 21 days. Two groups of rats were prophilactically treated before the procedure with the antioxidants vitamin E or L-NAME. We used two control groups, a sham group and another that did not experience surgery. In all cases the levels of ROS (circulating and hepatic), and the levels, activity and conformational features of plasma AT were evaluated. We also evaluated the intrahepatic distribution and features of AT and alpha1-AT. Results: Billiary cirrhosis produced a massive time-dependent increase of circulating and hepatic ROS that triggered the intracellular aggregation and retention of AT, leading to a circulating type I deficiency of the protein, associated with a mild increase of its latent form. This effect was similar for alpha1-AT. Treatment with antioxidants, especially L-NAME, reduced all the noxious conformational effects of massive oxidation. Conclusions: In conclusion, billiary cirrhosis-induced oxidative stress, although producing a mild increase of latent AT, does not produce significant alterations of the circulating AT molecule. However, this stress has pronounced conformational effects on the intracellular pool of hepatic serpins, leading to the retention of aggregated AT and alpha1-AT and the subsequent type I deficiency with the associated prothrombotic status. Treatment with antioxidants such as L-NAME reduce the noxious effects of high circulating levels of ROS and might prove potentially therapeutic.

P21 Therapeutic Efficacy of Plasmapheresis for the Treatment of Refractory Pruritis of Primary Billiary Cirrhosis: 2 Case Reports.

Primary billiary cirrhosis (PBC), a chronic cholestatic disease of presumed autoimmune aetiology, is characterised by progressive intrahepatic bile duct destruction, liver cirrhosis, failure, and death, unless treated by liver transplantation. Distressing pruritis (skin itch), fatigue and metabolic bone diseases frequently complicate this disease, significantly reducing quality of life. The pathogenesis of pruritis remains uncertain. Some unknown pruritogen(s) produced by the liver have been implicated which accumulate in the plasma as a result of chronic cholestasis. Recent evidence also suggests a central mechanism, with increased neurotransmission/neuromodulation mediated by endogenous opioid agonists. Therapeutic interventions include unabsorbable oral resins, urso‐deoxycholeic acid, opiate antagonists and rifampicin. More experimental therapies include: partial diversion of bile; charcoal haemoperfusion; UVA; plasmapheresis and albumin‐based dialysis (for patients with renal impairment). We used plasma exchange for the treatment of intractable pruritis in two patients with primary billiary cirrhosis. Both were females between ages of 50–60 years, refractory to all medical treatments and severely disabled by intractable pruritis and fatigue. In the first patient, weekly to fortnightly plasmapheresis considerably reduced the intensity of itch and stabilized her condition until her liver transplant. The second patient was treated for a relapse of PBC following her liver transplant. She significantly improved with more than 50% reduction in the intensity of her generalized itch with healing of excoriations, and was able to sleep for 4 h undisturbed after only one procedure. We suggest that plasmapheresis may be helpful for the pruritis of chronic cholestasis refractory to medical management. It could also be considered for the initial treatment of selected patients in combination with other therapies.

P0377 HEPATOPULMONARY SYNDROME IN CHILDREN: A SINGLE CENTRE EXPERIENCE

Introduction: Hepatopulmonary syndrome (HPS) is a rare complication of chronic liver disease or portal hypertension. The clinical presentation is dyspnoea on exertion or overt cyanosis. In the past, this complication contraindicated liver transplantation (LT). However, good outcome with reversal of symptoms after LT has been described. Methods: Single centre experience of management and outcome of HPS in 12 children. Results: Twelve children were diagnosed to have HPS on macroaggregated albumin (MAA) lung scintigraphy over a 15 year period (1988–2003), underlying liver disease being biliary atresia (BA) in 6, progressive intrahepatic cholestasis in 2, cryptogenic cirrhosis, billiary cirrhosis, portal vein sclerosis and alpha 1 antitrypsin deficiency in 1 each. Biliary atresia splenic malformation (BASM) syndrome was present in 3. There were 8 girls (65%) with a median (range) age at diagnosis of 6.6 years (1.4–15.4 years). All patients had clinical evidence of portal hypertension with 4 having a history of gastrointestinal bleeding. The presenting symptoms were dyspnoea (7), cyanosis (9)and clubbing (10). All children with BA had cleared their jaundice. Median (range) oxygen saturation by pulse oxymetry was 90% (56–95%) with mild increase on supplemental facial oxygen. MAA scintigraphy revealed median pulmonary shunting of 22% (range 4–49%). The degree of shunting was mild (<20%) in 5, moderate (20–40%) in 4 and severe (>40%) in 3. Cardiac echography revealed normal function of the heart in all. All children were listed for LT. Six children required oxygen therapy prior to LT. One child with BASM and a moderate shunt died of sepsis while awaiting LT. One child is currently listed for LT. Ten children underwent LT 6–20 months (median 12 months) after diagnosis of HPS. Six children were extubated after 24 hours with the longest period of ventilation being 10 days. Median (range) oxygen requirement after LT was 21 days (1–45 days). Two children died 1 week and 3.2 years post LT of multi-organ failure and post transplant lymphoproliferative disorder respectively. Nine children are alive and well 5.25 years (range 1 month-12.8 years) after diagnosis of HPS. Conclusion: HPS is reversible after LT and does not appear to complicate the postoperative course. Female preponderance in our study group remains unexplained but may be an effect of female sex hormones on pulmonary circulation.

Heat shock proteins are present in mallory bodies (cytokeratin aggresomes) in human liver biopsy specimens

Mallory bodies (MBs) are aggresomes, composed of cytokeratin and various other proteins, which form in diseased liver because of disruption in the ubiquitin-proteasome protein degradation pathway. Heat shock proteins (hsp’s) are thought to be involved in this process because it was discovered that MB formation is induced by heat shock in drug-primed mice. It has been reported that ubiquitin and a mutant form of ubiquitin (UBB +1) are found in aggresomes formed in the neurons in Alzheimer’s disease and in the liver MBs in various liver diseases. In addition, hsp 70 has been found in aggresomes in Alzheimer’s and in MBs in drug-primed mice. Therefore, we hypothesized that hsp’s might be involved in MB formation in human liver diseases. Liver biopsy sections were double-stained using ubiquitin and hsp 70 or 90b antibodies. Both hsps 70 and 90b were found in MBs in all liver diseases investigated including primary billiary cirrhosis, nonalcoholic steatohepatitis, hepatitis B and C, idiopathic cirrhosis, alcoholic hepatitis, and hepatocellular carcinoma. Ubiquitin and the hsp’s colocalized in all MBs in the diseased liver sections. These results indicate that hsp involvement in MB formation is similar to that seen in aggresome formation in other conformational diseases.

90 Endothelin-1 in experimental hepatopulmonary syndrome: evaluation in prehepatic portal hypertension, billiary and nonbiliary cirrhosis

90 Endothelin-1 in experimental hepatopulmonary syndrome: evaluation in prehepatic portal hypertension, billiary and nonbiliary cirrhosis

208 Increased donor age is associated with increased risk of recurrent primary billiary cirrhosis following liver transplantation

208 Increased donor age is associated with increased risk of recurrent primary billiary cirrhosis following liver transplantation

671 How is the loss of tolerance to mitochondrial autoantigens sustained in primary billiary cirrhosis?

671 How is the loss of tolerance to mitochondrial autoantigens sustained in primary billiary cirrhosis?

A global goodness-of-fit statistic for Cox regression models.

In this paper, a global goodness-of-fit test statistic for a Cox regression model, which has an approximate chi-squared distribution when the model has been correctly specified, is proposed. Our goodness-of-fit statistic is global and has power to detect if interactions or higher order powers of covariates in the model are needed. The proposed statistic is similar to the Hosmer and Lemeshow (1980, Communications in Statistics A10, 1043-1069) goodness-of-fit statistic for binary data as well as Schoenfeld's (1980, Biometrika 67, 145-153) statistic for the Cox model. The methods are illustrated using data from a Mayo Clinic trial in primary billiary cirrhosis of the liver (Fleming and Harrington, 1991, Counting Processes and Survival Analysis), in which the outcome is the time until liver transplantation or death. The are 17 possible covariates. Two Cox proportional hazards models are fit to the data, and the proposed goodness-of-fit statistic is applied to the fitted models.

Codeine for pruritus in primary billiary cirrhosis

Pruritus is a frequent and troublesome symptom in primary biliary cirrhosis (PBC). Increased plasma endogenous opioids play an important part in its pathogenesis and antagonists such as nalmefene are used in treatment; 1 Bergasa NV Schmitt JM Talbot TL et al. Open-label trial of oral nalmefene therapy for the pruritus of cholestatis. Hepatology. 1998; 27: 679-684 Crossref PubMed Scopus (160) Google Scholar their use is, however, limited by opioid withdrawal reactions. 2 Thorton JR Losowsky MS Opioid peptides and primary biliary cirrhosis. BMJ. 1988; 297: 1501-1504 Crossref PubMed Scopus (264) Google Scholar We report a 44-year-old woman with severe pruritus due to PBC who responded to codeine.

Autoantibodies profile in primary billiary cirrhosis

Autoantibodies profile in primary billiary cirrhosis

Autoantibodies profile in primary billiary cirrhosis

Autoantibodies profile in primary billiary cirrhosis