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none 55 si First published: 22 December 2016 Background: High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based. Aim: To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH. Methods: A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH. Results: Sixty surveys were sent, out of which 37 were returned. None reported budesonide as a first line induction agent for the acute presentation of AIH. Five (14%) participants reported using thiopurine S-methyltransferase measurements before commencement of thiopurine maintenance therapy. Thirteen (35%) routinely perform liver biopsy at 2 years of biochemical remission. If histological inflammatory activity is absent, four (11%) participants reduced azathioprine, whereas 10 (27%) attempted withdrawal altogether. Regarding the management of difficult-to-treat patients, mycophenolate mofetil is the most widely used second-line agent (n = ~450 in 28 centres), whereas tacrolimus (n = ~115 in 21 centres) and ciclosporin (n = ~112 in 18 centres) are less often reported. One centre reported considerable experience with infliximab, while rescue therapy with rituximab has been tried in seven centres. Conclusions: There is a wide variation in the management of patients with autoimmune hepatitis even among the most expert in the field. Although good quality evidence is lacking, there is considerable experience with second-line therapies. Future prospective studies should address these issues, so that we move from an expert- to an evidence- and personalised-based care in autoimmune hepatitis. mixed R. Liberal; Y. S. de Boer; R. J. Andrade; G. Bouma; G. N. Dalekos; A. Floreani; D. Gleeson; G. M. Hirschfield; P. Invernizzi; M. Lenzi; A. W. Lohse; G. Macedo; P. Milkiewicz; B. Terziroli; B. van Hoek; J. M. Vierling; M. A. Heneghan; on behalf of the International Autoimmune Hepatitis Group (IAIHG); A. Pares; A. J. Montano-Loza; A. Granito; A. E. Kremer; A. Floreani; A. W. Lohse; B. van Hoek; B. Terziroli; C. Schramm; C. Lammert; E. L. R. Cancado; E. Bjornsson; F. Lammert; G. N. Dalekos; G. Bouma; G. M. Hirschflield; G. Macedo; H. Hofer; I. Mackay; J. Neuberger; J. M. Vierling; J.P.H. Drenth; C.M.J. van Nieuwkerk; L. Muratori; M. Lenzi; M. Swain; M. Heneghan; M. Zeniya; O. Chazouilleres; P. Gines; P. Invernizzi; P. Milkiewicz; R. J. Andrade; R. Chapman; T. Berg; H. van Buuren; X. Ma R. Liberal; Y. S. de Boer; R. J. Andrade; G. Bouma; G. N. Dalekos; A. Floreani; D. Gleeson; G. M. Hirschfield; P. Invernizzi; M. Lenzi; A. W. Lohse; G. Macedo; P. Milkiewicz; B. Terziroli; B. van Hoek; J. M. Vierling; M. A. Heneghan; on behalf of the International Autoimmune Hepatitis Group (IAIHG); A. Pares; A. J. Montano-Loza; A. Granito; A. E. Kremer; A. Floreani; A. W. Lohse; B. van Hoek; B. Terziroli; C. Schramm; C. Lammert; E. L. R. Cancado; E. Bjornsson; F. Lammert; G. N. Dalekos; G. Bouma; G. M. Hirschflield; G. Macedo; H. Hofer; I. Mackay; J. Neuberger; J. M. Vierling; J.P.H. Drenth; C.M.J. van Nieuwkerk; L. Muratori; M. Lenzi; M. Swain; M. Heneghan; M. Zeniya; O. Chazouilleres; P. Gines; P. Invernizzi; P. Milkiewicz; R. J. Andrade; R. Chapman; T. Berg; H. van Buuren; X. Ma

Occult myeloproliferative disorders (MPD) are present in 25% of patients with chronic portal, splenic and mesenteric venous thrombosis (PSMVT). A somatic mutation of JAK2 (JAK2V617F) can be used to identify patients with latent MPD.We evaluated the prevalence and clinical significance of JAK2V617F in patients with chronic PSMVT.Allele-specific polymerase chain reaction was performed to screen for JAK2V617F.Thirty-five patients were tested for JAK2V617F. The underlying pro-coagulant condition was MPD in seven of 35 (20.0%) patients; other aetiologies included hereditary thrombophilia (n = 5), chronic pancreatitis (n = 2), liver abscess (n = 1) and umbilical vein sepsis (n = 3). The remainder were labelled idiopathic, i.e. 17/35 (48.6%) patients. JAK2V617F was detected in 16/35 (45.7%) patients: seven of seven (100%) with MPD, two of 11 (18.1%) with non-MPD acquired conditions and seven of 17 (41.2%) with 'idiopathic' chronic PSMVT. Mean haemoglobin concentration (P = 0.04), haematocrit (P = 0.04), white cell count (P = 0.002) and platelet count (P = 0.05) were significantly higher in patients with JAK2V617F. None of the seven patients with latent MPD have progressed to overt MPD over median follow-up of 85 months.JAK2V617F occurs in 41% of patients with idiopathic chronic portal, splenic and mesenteric venous thrombosis, confirming the presence of latent myeloproliferative disorders, and should form part of the routine pro-coagulant screen.

The management of autoimmune hepatitis (AIH) continues to be refined. However, several issues remain unresolved, primarily as a consequence of the low incidence of the disease. This factor has contributed both to a lack of understanding of and a paucity of large scale clinical trials involving therapeutic agents.To summarize the latest evidence regarding the pathogenesis, diagnosis, therapy and long-term management of AIH with a focus on clinical aspects of the disease.We searched PUBMED for articles pertaining to AIH, its pathogenesis, treatment and clinical outcomes, combined with the authors' own knowledge of the literature.Standard therapy (corticosteroids and azathioprine) is effective in more than 80% of patients which renders study of novel agents difficult. Budesonide appears to show equivalence to prednisolone. Available, but limited, data suggest that mycophenolate mofetil, tacrolimus and ciclosporin are all variably effective second line agents. Patients with AIH and cirrhosis are at risk of hepatocellular carcinoma (HCC) and require screening. Patients with end stage liver disease represent excellent candidates for liver transplantation.Despite ongoing limitations in the understanding of pathogenesis and difficulties in evaluating novel therapies, the management of AIH continues to evolve slowly. Multi-centre collaboration is necessary to obtain sufficient patient numbers to undertake good quality therapeutic studies.

All aspects of hepatology were represented at this year's meeting of the American Association for the Study of Liver Diseases (AASLD), although the meeting was dominated by a proliferation of information in the arena of viral hepatitis. In an international multicenter study of over 1000 treatment-naive patients with hepatitis C virus (HCV) infection, sustained virological response was found in 56% of patients who received PEGylated interferon (IFN) alpha-2a (Pegasys; F Hoffmann-La Roche) in combination with ribavirin (Virazole; ICN Pharmaceuticals), versus 45% in patients who received IFN alpha-2b and ribavirin therapy, and 30% of patients who received PEG. This is a significant improvement on currently licensed therapy and will define practice patterns for the next decade. In other areas, novel therapies such as silymarin for cholestatic liver disease, L-dT (Novirio Pharmaceuticals Inc), herbal therapy, combination therapies including amantadine and mycophenolate mofetil (Roche Holding) for viral hepatitis, and long-acting octreotide (Sandostatin LAR Depot; Novartis) for portal hypertension, were presented. This review represents the best of AASLD at DDW 2001.

Fas-expressing cytotoxic T lymphocytes (CTLs) are important antitumor immune effector cells in patients with hepatocellular carcinoma (HCC). The role of transforming growth factor beta 1 (TGF-beta1) in modulating the expression of Fas by CTLs is not known in HCC. The objectives of this study were to characterize the expression of Fas by CTLs and natural killer (NK) cells among peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) in patients with HCC and to correlate the association, if any, with serum TGF-beta1 levels.PBLs from 18 patients with HCC and TILs from 5 HCC liver specimens were isolated, and Fas expression was analyzed by three-color flow cytometry. The results were compared with results from normal control volunteers (n = 19 individuals). Serum TGF-beta1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay.The median percentage of Fas expression by CD3 positive T cells was significantly higher in patients with HCC compared with normal controls (54.37% vs. 32.03%, respectively; P = 0.0036), and this was attributable solely to Fas expression by CD4 positive PBLs (54.46% vs. 34.90%, respectively; P = 0.0234). In contrast, Fas expression was significantly higher in all the subtypes of TILs (CD3 positive, CD4 positive, CD8 positive, NK cells, and natural T cells) compared with controls (all P values were0.001). Tumor size was inversely proportional to the TGF-beta1 levels (correlation coefficient [r] = -0.725; P0.0001), which were correlated inversely with Fas expression by CD4 positive PBLs (r = -0.516; P = 0.01).In patients with HCC, TILs exhibit significantly increased expression of Fas compared with PBLs that may enhance their susceptibility to apoptotic mechanisms. Larger tumors were associated with lower serum TGFbeta1 levels, and this was correlated with greater Fas expression by CD4 positive PBLs.

Editor,—In a recent issue of Gut , Zheng et al reported that peptic ulcer disease was associated with increased expression of Lewis (Le) antigens but not cagA , iceA , or vacA in Chinese patients infected with Helicobacter pylori ( (2000) Gut 47:18–22. [OpenUrl][1][Abstract/FREE Full Text][2] ). These data raise as many questions as they answer and add further controversy to an intriguing area of microbiology and gastroenterology. Lex and/or Ley blood group determinants are commonly found on the lipopolysaccharide (LPS) of H pylori isolates. These determinants have been identified on approximately 80–90% of isolates from all patient series examined to date.1-3 In our own series, 74/84 (88%) isolates expressed either Lex or Ley, with 47/84 (56%) of isolates coexpressing both determinants.4 No difference was identified in the prevalence of Lex or Leyexpression on H pylori strains isolated from ulcer patients and those strains isolated from patients with chronic gastritis, nor was an association demonstrated between host and bacterial Lewis phenotype. Since the report of Zheng et al we have reviewed our raw data regarding the prevalence of strains expressing two or more Lewis antigens. We found that two or more Le determinants were present in 9/12 … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BClinical%2BMicrobiology%26rft.stitle%253DJ.%2BClin.%2BMicrobiol.%26rft.aulast%253DSimoons-Smit%26rft.auinit1%253DI.%2BM.%26rft.volume%253D34%26rft.issue%253D9%26rft.spage%253D2196%26rft.epage%253D2200%26rft.atitle%253DTyping%2Bof%2BHelicobacter%2Bpylori%2Bwith%2Bmonoclonal%2Bantibodies%2Bagainst%2BLewis%2Bantigens%2Bin%2Blipopolysaccharide%26rft_id%253Dinfo%253Apmid%252F8862584%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jcm&resid=34/9/2196&atom=%2Fgutjnl%2F48%2F6%2F869.1.atom

Cholestasis is a common finding after liver transplantation and usually signifies graft dysfunction. The most important factor in the evaluation of patients with cholestasis is an awareness of the disorders that commonly arise along a time continuum post-transplant. Therefore, the approach to cholestasis requires a systematic review of biochemical, histological, and radiographic data. This article considers the causes of cholestasis in liver transplant recipients, excluding those associated with biliary anastomotic stricturing. These causes include conditions as diverse as ischemia reperfusion injury, ABO blood group incompatibility, hepatic arterial thrombosis, cytomegalovirus infection, fibrosing cholestatic hepatitis secondary to hepatitis B and C viruses, recurrent primary sclerosing cholangitis, recurrent primary biliary cirrhosis, and chronic rejection. Also examined are management issues pertinent to these conditions and strategies used in preventing or diminishing the effects of cholestasis once established.

Disturbance of the circulatory system frequently occurs in patients with cirrhosis. Cardiac index and plasma volume increase whereas mean arterial blood pressure and systemic vascular resistance decrease. Marked disturbance in vasoconstrictor and natriuretic systems also exist with activation mediators such as plasma renin, plasma noradrenaline, antidiuretic hormone and endothelin. Renal factors contribute to the pathogenesis of ascites formation although the exact mechanisms are yet to be elucidated. Several theories exist in relation to pathogenesis although none to date fully explain all of the findings observed in clinical practice. In this review, we examine the mechanisms that contribute to the development of ascites in patients with cirrhosis and portal hypertension.

Although some form of myocyte damage is probably the main abnormality responsible for heart failure in dilated cardiomyopathy, abnormalities of the supporting interstitial collagen meshwork also occur. To see if abnormal collagen could be detected in cardiomyopathic hearts, which did not have interstitial fibrosis by routine light microscopy, we examined interstitial collagen using scanning electron microscopy and a novel digestion technique. Cardiomyopathetic collagen fibrils were significantly thicker and more densely packed than normal. We conclude that an ultrastructural collagen abnormality occurs early in dilated cardiomyopathy, this abnormality may contribute to the pathophysiology of this disease.

Fifty sporadic colorectal carcinomas diagnosed in 1991 were analysed for microsatellite instability at four loci. Five of 50 (10 per cent) tumours showed replication errors (RERs) at two or more loci and were classed as RER-positive (RER+). A further five showed RERs at one locus only. A significant association (Fisher exact test) was found between RER+ tumours and location in the proximal colon, exophytic shape, size5 cm, histological margin, lymphoid reaction, and near-diploid DNA content. There was no significant difference for age, sex, grade, mucin production, p53 protein overexpression or Duke's stage. There was no significant difference in survival as measured over a 60-month follow-up period. The findings, though limited by the small case numbers involved, show an association between RER positivity in sporadic colorectal tumours and certain clinico-pathological features. They do not suggest a better clinical outcome for sporadic RER+ tumours.

Thromboembolic events frequently complicate the clinical course of patients with inflammatory bowel disease (IBD). Hereditary thrombophilia may contribute to this tendency. Resistance to activated protein C is the most recently described thrombophilic state and may account for up to 40% of patients with thrombophilia. Thirty-seven patients with IBD were studied (mean age 44 years, range 18-82 years). Three patients had a history of thrombotic episodes. The 37 controls included 23 men and 17 women (mean age 48 years, range 16-89 years). Disease activity was assessed using the Harvey Bradshaw index for patients with Crohn's disease and the Truelove and Witts grading system for patients with ulcerative colitis. Levels of fibrinogen, antithrombin III (ATIII), protein C, protein S, activated protein C resistance (APCR), and the presence of a lupus anticoagulant (LA) were determined. Median ATIII levels in patients with IBD were significantly lower than controls (98% vs 106%, P = 0.007), while fibrinogen was elevated (4.2 vs 3.3 g/liter, P = 0.026) despite quiescent disease activity. LA was detected in 7/37 patients in the IBD group compared to 0/37 controls. (chi2 = 5.68, P = 0.017). No significant difference was observed in levels of inherited thrombophilic factors and in particular APCR between IBD patients and controls. In conclusion, the presence of inherited thrombophilic defects, in particular APCR, is uncommon in patients with IBD and does not merit routine screening.

The use of 14C-urea breath testing for diagnosis of Helicobacter pylori infection in gastric mucosa has gained widespread acceptance and utilisation. We evaluated a 14C urea breath test (UBT) in 116 patients undergoing endoscopy. Seventy four patients were administered 185 kBq (5 mCi-conventional dose), and 42 patients reduced dose (92.5 IBq, 2.5 mCi) of 14C-urea. All were tested for H. pylori using culture, direct microscopy of gastric biopsies and histological evaluation of paraffin stained sections. Using the mean + three standard deviations as the cut-off value, a sensitivity of 96% and specificity of 100% was found for the conventional dose test. At reduced dose, sensitivity was 100% and specificity 96%. Positive and negative predictive values were 100% and 93% for the conventional dose test, and 96% and 100% for testing at reduced dose. We conclude that the UBT is a simple, non-invasive and useful diagnostic alternative for detection of H. pylori in infected patients. We advocate its use in patients less than 45 years of age without alarm symptoms, and also in cases where the need for endoscopic evaluation is not vital, such as after eradication therapy.

AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.

Retrocalcaneal bursitis is a distinct condition causing posterior heel pain in active, healthy children. It appears to result from post-traumatic inflammation of the soft tissues of the posterior heel, and is unrelated to avascular necrosis of the calcaneal apophysis. The diagnosis may be confirmed radiographically by the loss of the lucent retrocalcaneal recess, with a normal Achilles tendon and superficial soft tissue contour, and intact cortex of the underlying os calcis.

Haglund syndrome is a common cause of posterior heel pain, characterized clinically by a painful soft-tissue swelling at the level of the achilles tendon insertion. On the lateral heel radiograph the syndrome is characterized by a prominent calcaneal bursal projection, retrocalcaneal bursitis, thickening of the Achilles tendon, and a convexity of the superficial soft tissues at the level of the Achilles tendon insertion, a "pump-bump." An objective method for evaluating prominence of the bursal projection is measurement using the parallel pitch lines. This measurement helps to identify patients with Haglund syndrome and patients predisposed to develop this condition, and also to differentiate local causes of posterior heel pain from systemic causes. The parallel pitch line measurement was determined in 10 symptomatic feet and 78 control feet and the results were analyzed statistically.

Significant changes in the radiographic features of bronchopulmonary dysplasia (BPD) have accompanied recent advances in treatment of neonatal respiratory distress syndrome. Retrospective study of 709 newborns showed atypical radiographic findings in many patients with clinical BPD. While 12/20 infants with clinical BPD showed changes identical to Northway's stage 4 disease, the remaining 8 (40% of patients with significant respiratory dysfunction) had diffuse, fine infiltrates without emphysema. Radiographic progression from RDS through all Northway stages was observed in only 4 patients. Diagnosis of stage 2 BPD was complicated by the presence of PDA in 9/17 cases. Stage 3 BPD was identified with certainty in only 5 infants, but may have coexisted with PIE in as many as 22 cases. Nevertheless, there was close agreement between the radiographic findings and clinical severity of chronic lung disease. Mild (type 1) infiltrates following RDS may be distinguished from chronic pulmonary insufficiency of prematurity (CPIP) or "immature lung." In patients who require only short-term supplemental O2, type 1 changes may reflect delayed resolution of RDS in an underdeveloped lung. These same findings in infants with prolonged O2 dependence usually indicate a mild form of BPD. Coarse infiltrates and emphysema (type 2) are almost always associated with severe respiratory impairment.

Inflammatory pseudotumor (IPT) of the liver and intrahepatic bile ducts is a rare cause of obstructive jaundice and portal hypertension in the pediatric age group. Because it seems to have a better long-term outcome than many of the conditions with which it may be confused, it is important to recognize the radiologic and pathologic features of this rare lesion so that appropriate therapy may be instituted.

Haglund syndrome, a common cause of pain in the posterior heel, consists of a painful swelling of the local soft tissues (the so-called pump bump) and prominence of the calcaneal bursal projection. The condition is caused by compression of the distal Achilles tendon and surrounding soft tissue between the os calcis and the posterior shoe counter. Osseous plantar projections appear to be a critical etiologic factor in Haglund syndrome. With an experimental model, it has been demonstrated that osseous projections on the plantar surface of the calcaneus adversely influence the bone-soft tissue relation of the posterior heel. Shoe heel elevation has been shown to be clinically effective in alleviating symptoms. It is demonstrated with an experimental model that elevation of the shoe heel decreases the pitch angle. This diminishes the prominence of the bursal projection and allows the foot to slip forward, displacing the posterior calcaneus away from the shoe counter.