Budd-Chiari syndrome: reassessment of a step-wise treatment strategy.

BACKGROUND AND STUDY AIMS: The Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction. A step-wise management was recently proposed. The aim of this study is to reassess our treatment approach and long-term outcome. PATIENTS AND METHODS: The data of 37 Budd-Chiari patients, seen in our unit, were critically analyzed and compared with the ENVIE (European Network For Vascular Disorders of the Liver) data. RESULTS: Most patients had multiple prothrombotic conditions (41%), of which an underlying myeloproliferative neoplasm was the most frequent (59%). The JAK2V617F mutation was associated with more complete occlusion of all hepatic veins (JAK2 mutation +: 70% vs JAK2 mutation -: 23% and a higher severity score. The step-wise treatment algorithm used in our unit, in function of the severity of the liver impairment and the number and the extension of hepatic veins occluded, resulted in the following treatments: only anticoagulation (n = 7.21%), recanalization procedure (n = 4.21%), portosystemic shunts (n = 9.26%) and liver transplantation (n = 14.44%). This resulted in a 10 year survival rate of 90%. Treatment of the underlying hemostatic disorder offered a low recurrence rate. None of the 21 patients with a myeloproliferative neoplasm died in relation to the hematologic disorder. CONCLUSIONS: An individualized treatment regimen consisting of anticoagulation and interventional radiology and/or transplantation when necessary and strict follow-up of the underlying hematologic disorder, provided an excellent long-term survival, which confirm the data of the ENVIE study.

South African guideline for the management of chronic hepatitis B: 2013.

Hepatitis B remains a significant yet preventable health issue in South Africa. The introduction of the hepatitis B vaccine into the country some 18 years ago has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg positivity remain unacceptably high. Those with chronic hepatitis B virus infection have an elevated risk of developing cirrhosis with end-stage liver disease and a markedly elevated risk of hepatocellular carcinoma, independent of the presence of cirrhosis. The challenge in South Africa remains prevention through the universal vaccination coverage of all children and the identification of those with chronic hepatitis B virus infection. Over the last decade our understanding of hepatitis B and its behaviour and natural history in those with chronic infection has significantly improved. This understanding is key to identifying those who warrant further evaluation and therapy. A number of global societies have updated their guidelines in recent years. This document draws on these guidelines and serves to contextualise, for South Africa, practice guidelines for the management of chronic hepatitis B.

6-Thioguanine treatment in inflammatory bowel disease: a critical appraisal by a European 6-TG working party.

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity.

A large-scale automated method for hepatocyte isolation: effects on proliferation in culture.

Large-scale sterile methods for isolating hepatocytes are desirable for the development of bioartificial liver support systems. In this study the traditional centrifuge method was compared with the use of a Baylor Rapid Autologous Transfusion (BRAT) machine for isolating large quantities of porcine hepatocytes. After isolating hepatocytes, the methods were evaluated in terms of cell viability and yield per liver, proliferation over 7 days, and the effects on the cell cycle using the trypan blue exclusion test, conventional phase-contrast light microscopy, the lactate to pyruvate ratio, the leakage of lactate dehydrogenase (LD) and aspartate aminotransferase (AST), lidocaine clearance, albumin production, and flow cytometry. With the centrifuge method the mean cell viability was 92.5%, while with the BRAT method the viability was 95.9%. The minimal cell yields with the BRAT procedure were 7.3 x 10(9) for 250-ml centrifuge bowls and 2.8 x 10(9) for 165-ml bowls, which compares well with that found by other authors. Because the same initial procedures were employed in both methods the total hepatocyte yield per liver was comparable. Flow cytometry confirmed that the proliferation of hepatocytes was facilitated by oxygenation during the isolation procedure. The recovery of hepatocytes in culture following isolation was similar after either method. Daily microscopic investigation indicated that cytoplasmic vacuolization and granularities were present after either procedure and these disappeared following 3-4 days of culturing. Flow cytometry indicated that the hepatocyte cell cycle was similar after either method; at 7 days the profile indicated that the cells were still proliferating. Trends in the lactate to pyruvate ratio and the leakage of LD and AST indicated that the functional polarity of hepatocytes was regained after approximately 3 days. Lidocaine clearance at 4 days indicated that the cytochrome P450 system was active, while significant albumin production was apparent at day 5. The benefit of using BRAT technology in hepatocyte isolation lies in guaranteed sterility, convenience, speed, and the ability to oxygenate media and cell suspensions during the procedure.

Quantitation of hydroxyproline in bone by gas chromatography-mass spectrometry.

A validated gas chromatography (GC)-mass spectrometric (MS) method for the analysis of hydroxyproline in rat femur is reported. Hydroxyproline in bone hydrolysates was extracted with an anion exchange resin and the N(O)-tert-butyldimethylsilyl derivatives analyzed by GC-MS. The hydroxyproline concentration was estimated relative to pipecolic acid, 3,4-dehydroproline and n-tetracosane as internal standards. The mass-to-charge ratios (m/z) for the ions used for quantitation by single ion monitoring were 314 m/z for hydroxyproline, 198 m/z for pipecolic acid, 256 m/z for dehydroproline and 57 m/z for n-tetracosane. A coefficient of variation of 5.8% was achieved and the limit of detection was calculated to be 0.233 micromol/l bone hydrolysate.

Distal embolization and local vessel wall ulceration after gastric variceal obliteration with N-butyl-2-cyanoacrylate: a case report and review of the literature.

Repeated endoscopic injections of N-butyl-2-cyanoacrylate mixtures into large gastric varices in a single patient led to two complications: initially, pulmonary embolism, and later local ulceration of the wall of a varix. The latter resulted in massive uncontrollable hemorrhage that ultimately led to a fatal outcome. This case report also analyzes complications reported in the literature during similar endoscopic procedures for gastric varices.

Hepatic osteodystrophy in rats results mainly from portasystemic shunting.

BACKGROUND AND AIMS: In chronic liver disease, bone disease frequently develops. The contributions of the different features of liver disease such as parenchymal inflammation, portal hypertension, and portasystemic shunting on bone metabolism have not been systematically studied. The aim of this study was to identify the features of liver disease contributing to bone disease using rat models. METHODS: Parenchymal liver disease was induced by carbon tetrachloride administration, portal hypertension by partial portal vein ligation, and portasystemic shunting by end to side anastomosis of the portal vein to the inferior vena cava. Normal and sham operated surgical animals served as controls. Serum calcium, 25-hydroxy vitamin D (25-OH vit D), and osteocalcin levels, and urinary deoxypyridinoline excretion were analysed. Testosterone and oestradiol levels were determined in male and female rats, respectively. Interleukin 1, interleukin 6, and tumour necrosis factor alpha (TNF-alpha) were determined in serum. Bone density was measured in all groups and in addition, in the surgical groups, histomorphometry was performed on undecalcified specimens of the proximal tibia. The calcium content of the femurs, removed at termination and ashed, was determined. RESULTS: Early parenchymal disease and portal hypertension did not affect bone metabolism or body mass. Portasystemic shunting increased bone resorption, decreased bone formation, bone density, and trabecular bone volume which were commensurate with a reduction in body mass. TNF-alpha levels were elevated and testosterone levels were low in male portasystemic shunted rats. CONCLUSIONS: Portasystemic shunting in the rat adversely affects bone metabolism as part of a generalised catabolic state where high TNF-alpha and low testosterone and 25-OH vit D levels may play a role.

Evaluation of a novel heminested PCR assay based on the phosphoglucosamine mutase gene for detection of Helicobacter pylori in saliva and dental plaque.

A novel heminested PCR protocol was developed for the specific detection of Helicobacter pylori at low copy numbers. A set of primers specific for the phosphoglucosamine mutase gene (glmM) of H. pylori produced a 765-bp fragment that was used as template for the heminested primer pair delineating a 496-bp fragment. By using agarose gel electrophoresis for detection of the heminested PCR-amplified products, amplification of H. pylori genomic DNA was achieved at concentrations as low as 0.1 pg, equivalent to 5 x 10(2) bacteria. A study was subsequently undertaken to evaluate the heminested PCR for detection of H. pylori in dental plaque and saliva. Specimens collected from 58 individuals were cultured, and PCR was subsequently performed on the oral cultures. Identification of H. pylori in the same series of saliva and dental plaque specimens was carried out with PCR using a primer pair specific for the H. pylori urease B gene and by the heminested PCR assay. The identity of the amplified products was confirmed by DNA sequencing. Our results demonstrate that the heminested PCR assay was specific for detection of H. pylori, yielding no false-positive results, and that H. pylori had a low prevalence (approximately 3%) in specimens obtained from the oral cavity.

Anaerobic bacteremia and necrotizing fasciitis in a patient with Crohn's disease.

Crohn's disease is a chronic, granulomatous disease that affects the gut that is frequently treated with immunosuppressive therapy. Infectious complications are common and are usually related to the transmural nature of the inflammation, frequently manifesting as abscesses or perianal sepsis. Necrotizing fasciitis has not been reported in Crohn's disease. A case of a fatal necrotizing fasciitis in a patient with Crohn's disease after gut biopsies and corticosteroid therapy is reported.

Hepatic osteodystrophy: the influence of liver disease and portal hypertension on cytokine activation.

Chronic liver disease is frequently complicated by bone disease. The mechanisms leading to bone-loss are unknown but are probably not related to abnormal vitamin D metabolism. The effects of portal hypertension and porto-systemic shunting on bone-loss have not been studied. It is postulated that liver disease, or the complications of liver disease (portal hypertension or porto-systemic shunting), might be responsible for the activation of cytokines. It is further postulated that these cytokines might be the final common pathway leading to bone-loss in both parenchymal and cholestatic liver disorders by modifying osteoblast or osteoclast function.

An adaptation of the Moyers mixed dentition space analysis for a Western Cape Caucasian population.

200 dental plaster casts of Western Cape Caucasoid subjects, all of whom were under the age of 21 years, were used in this study. Mesio-distal measurements (MD lengths) were obtained of all the teeth, disregarding the third molars. This data was used to develop regression equations, for maxillary and for mandibular arches, to enable the prediction of the mesio-distal lengths of the canine and two premolars. The study identified the sum of the MD lengths of the permanent lower incisors as the best predictor. It appears that separate predictions for male and female are not warranted. The equations and the predicted values were compared with those of Moyers (1973 and 1988) and some significant differences were found. The Prediction Tables will be useful in analysis of the mixed dentition phase in patients from this population group.