Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis.

OBJECTIVES: Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment. METHODS: We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin). RESULTS: Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07). CONCLUSIONS: Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

Change in awareness of gluten-related disorders among chefs and the general public in the UK: a 10-year follow-up study.

BACKGROUND AND OBJECTIVES: In view of the increasing popularity of a gluten-free diet, we sought to determine whether there has been a change in awareness of gluten-related disorders (GRD) among the general public and chefs. MATERIALS AND METHODS: A face-to-face questionnaire on coeliac disease (CD) and gluten sensitivity (GS) was performed on the general public and chefs based in Sheffield, UK. The assessment was first carried out in 2003 and repeated in 2013. RESULTS: In total, 513 public members in 2003 (mean age 49.2 years, 62% women) were compared with 575 public members in 2013 (mean age 37.8 years, 57% women). There was a significant increase in the public's awareness of GRD from the years 2003 to 2013, CD [44.2% to 74.4%, adjusted odds ratio (AOR) 3.9; 95% confidence interval (CI) 3.0-5.19] and GS (58.3% to 89%, AOR 7.1; 95% CI 5.0-9.98; P<0.001). Also, 322 chefs in 2003 (mean age 37.6 years, 15% women) were compared with 265 chefs in 2013 (mean age 27.1 years, 38% women). There was a significant increase in chefs' awareness of GRD from the years 2003 to 2013, CD (17.1% to 78.1%, AOR 12.5; 95% CI 7.9-19.6) and GS (9.3% to 87.5%, AOR 65.7; 95% CI 35.4-122; P<0.001). Whereas in 2003 the public were significantly more aware of GRD than chefs, by 2013, this had reached a similar prevalence in both groups. In addition, the correct recognition of the gluten-free symbol was 44% for the public and 40% for chefs (P=0.28). Gluten-free products were sold by 41% of restaurants and 27% of takeaways (P=0.07). CONCLUSION: There has been a marked increase in both the public's and chefs' awareness of GRD. Such findings may ease the social phobia that individuals with GRD have traditionally been accustomed to.

Khat (Catha Edulis) as a possible cause of autoimmune hepatitis.

AIM: To investigate the potential role of khat in triggering auto immune hepatitis. METHODS: Patients with a history of khat use and acute hepatitis were identified using the computer database in the hepatology department at the Royal Hallamshire Hospital. They were then assessed for probability of having autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria. RESULTS: Six patients were identified. All of them had presented with acute hepatitis on a background of khat. All were male and five of these patients were of Somali origin, while one patient was from Yemen. The patients were given points on the modified autoimmune hepatitis score which is based on their liver enzymes, autoimmune screen, exclusion of viral hepatitis alcohol and drugs, immunoglobulin levels and liver histology. The patients were given a score of -4 for khat use due to its potential to cause drug induced liver injury. Five of these patients scored between 10 and 15 points, placing them in the probable group for having autoimmune hepatitis. All of these patients were treated with prednisolone and demonstrated a good response to immunosuppression. CONCLUSION: One possibile cause of hepatotoxicity with khat could be via triggering of autoimmune hepatitis in a genetically susceptible individual. Further studies are needed for confirmation.

Refractory bleeding from portal hypertensive gastropathy: a further novel role for thalidomide therapy?

Bleeding from portal hypertensive gastropathy (PHG) can pose a therapeutic challenge. Thalidomide, which selectively inhibits tumour necrosis factor-alpha production by enhancing messenger RNA degradation, has been shown to reduce portal venous pressure in cirrhotic and non-cirrhotic portal hypertension. Thalidomide is also a potent inhibitor of angiogenesis. We describe a case of intractable bleeding from PHG secondary to extrahepatic portal vein obstruction due to malignancy, which was managed successfully by thalidomide, thus obviating the need for major surgery. Although the use of thalidomide for treatment of severe intestinal bleeding has been described previously, this is the first case report, to our knowledge, describing its efficacy in bleeding secondary to PHG. We discuss the possible therapeutic mechanisms for thalidomide in PHG.

Chefs' knowledge of coeliac disease (compared to the public): a questionnaire survey from the United Kingdom.

BACKGROUND: For patients with coeliac disease (CD), compliance with a gluten-free diet, when eating food not prepared at home may be difficult. AIMS: We assessed whether there are differences in the eating habits of coeliac patients when compared to the general public. In addition, we compared chefs' knowledge with the public's knowledge about CD. METHOD: A questionnaire survey about CD was performed on coeliac patients, chefs and the general public from the United Kingdom (UK). RESULTS: Three hundred and nineteen coeliac patients [mean age 53.8 years, 65.8% female], 513 members of the public [49.2 years, 62.6% female] and 322 chefs [37.6 years, 15.2% female] were interviewed. Chefs were less likely to have heard of CD when compared to the public (17.1% (55/322) versus 44.2% (227/513), respectively, P<0.0001). Coeliac patients ate less frequently at a friend's house than the general public (P = 0.003). Coeliac patients ate less frequently from take-away establishments (P<0.0001). However, coeliac patients' ate as frequently in restaurants (P = 0.078). CONCLUSIONS: In the UK, chefs appear to know less about CD than the general public. Patients with CD feel justifiably cautious when eating food not prepared at home. Educating chefs about a gluten-free diet may alleviate the social restrictions on coeliac patients.