Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment.

Purpose To determine whether alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic hepatitis B virus (HBV) infection. Data sources Randomized controlled studies published in the English literature between January 1966 and June 1992 were identified through a MEDLINE computer search. Study selection Fifteen randomized controlled studies with a total of 837 adult chronic HBV carriers who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were identified. Studies were included if patients were treated for at least 3 months and followed for at least 6 months after cessation of therapy. Results Overall, the loss of HBsAg occurred 6% more often in interferon-treated patients than the natural seroconversion seen in controls (7.8% compared with 1.8%, P = 0.001), and the loss of viral replication occurred approximately 20% more often in treated patients than in controls (33% compared with 12% for loss of HBeAg and 37% compared with 17% for the loss of HBV DNA, P = 0.0001) if patients received interferon for 3 to 6 months and were followed for 6 to 12 months. Interferon also had a significant treatment effect on the development of antibodies to HBsAg (anti-HBs), antibodies to HBeAg (anti-HBe), and on the normalization of alanine aminotransferase levels. Conclusions Alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic HBV infection who are HBeAg positive when these patients are treated for 3 to 6 months and followed for 6 to 12 months after cessation of therapy. Follow-up studies are required to determine whether interferon reduces the risk for developing cirrhosis or hepatocellular carcinoma.

Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.

Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its localization in high amounts both in the small intestinal epithelium and liver makes it a major contributor to presystemic elimination following oral drug administration. Drug interactions involving enzyme inhibition or induction are common following the coadministration of two or more CYP3A substrates. Studies using in vitro preparations are useful in identifying such potential interactions and possibly permitting extrapolation of in vitro findings to the likely in vivo situation. Even if accurate quantitative predictions cannot be made, several classes of drugs can be expected to result in a drug interaction based on clinical experience. In many instances, the extent of such drug interactions is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs.

http://www3.uah.es/farmamol/Public/AnnReviews/PDF/Pharma_Toxicol/Human_Cyp3A.pdf

In vitro and in vivo drug interactions involving human cyp3a

Small-bowel capsule endoscopy (SBCE)
 1 ESGE recommends that prior to SBCE patients ingest a purgative (2 L of polyethylene glycol [PEG]) for better visualization. Strong recommendation, high quality evidence. However, the optimal timing for taking purgatives is yet to be established. 2 ESGE recommends that SBCE should be performed as an outpatient procedure if possible, since completion rates are higher in outpatients than in inpatients. Strong recommendation, moderate quality evidence. 3 ESGE recommends that patients with pacemakers can safely undergo SBCE without special precautions. Strong recommendation, low quality evidence. 4 ESGE suggests that SBCE can also be safely performed in patients with implantable cardioverter defibrillators and left ventricular assist devices. Weak recommendation, low quality evidence. 5 ESGE recommends the acceptance of qualified nurses and trained technicians as prereaders of capsule endoscopy studies as their competency in identifying pathology is similar to that of medically qualified readers. The responsibility of establishing a diagnosis must however remain with the attending physician. Strong recommendation, moderate quality evidence. 6 ESGE recommends observation in cases of asymptomatic capsule retention. Strong recommendation, moderate quality evidence. In cases where capsule retrieval is indicated, ESGE recommends the use of device-assisted enteroscopy as the method of choice. Strong recommendation, moderate quality evidence. Device-assisted enteroscopy (DAE)
 1 ESGE recommends performing diagnostic DAE as a day-case procedure in patients without significant underlying co-morbidities; in patients with co-morbidities and/or those undergoing a therapeutic procedure, an inpatient stay is recommended. Strong recommendation, low quality evidence The choice between different settings also depends on sedation protocols. Strong recommendation, low quality evidence. 2 ESGE suggests that conscious sedation, deep sedation, and general anesthesia are all acceptable alternatives: the choice between them should be governed by procedure complexity, clinical factors, and local organizational protocols. Weak recommendation, low quality evidence. 3 ESGE recommends that the findings of previous diagnostic investigations should guide the choice of insertion route. Strong recommendation, moderate quality evidence. If the location of the small-bowel lesion is unknown or uncertain, ESGE recommends that the antegrade route should be generally preferred. Strong recommendation, low quality evidence. In the setting of massive overt bleeding, ESGE recommends an initial antegrade approach. Strong recommendation, low quality evidence. 4 ESGE recommends that, for balloon-assisted enteroscopy (i. e., single-balloon enteroscopy [SBE] and double-balloon enteroscopy [DBE]), small-bowel insertion depth should be estimated by counting net advancement of the enteroscope during the insertion phase, with confirmation of this estimate during withdrawal. Strong recommendation, low quality evidence. ESGE recommends that, for spiral enteroscopy, insertion depth should be estimated during withdrawal. Strong recommendation, moderate quality evidence. Since the calculated insertion depth is only a rough estimate, ESGE recommends placing a tattoo to mark the identified lesion and/or the deepest point of insertion. Strong recommendation, low quality evidence. 5 ESGE recommends that all endoscopic therapeutic procedures can be undertaken at the time of DAE. Strong recommendation, moderate quality evidence. Moreover, when therapeutic interventions are performed, additional specific safety measures are needed to prevent complications. Strong recommendation, high quality evidence.

/pdf/small-bowel-capsule-endoscopy-and-device-assisted-4dltzyt3z1.pdf

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

https://www.spg.pt/wp-content/uploads/2015/11/2013-JCC_ECCO_Endoscopy_Consensus_10_2013_inPress.pdf

European evidence based consensus for endoscopy in inflammatory bowel disease

Effective palliation of malignant biliary obstruction with conventional 10 or 12 French gauge straight polyethylene endoprostheses is limited by stent occlusion, which typically occurs four to five months after insertion. Short term follow up studies of self expanding metal stents (Wallstent, Schneider, UK) in the treatment of patients with malignant biliary obstruction have shown that their use is associated with fewer episodes of stent occlusion compared with plastic stents. There are few data, however, on the longterm patency and durability of metal stents in malignant disease. Between May 1989 and May 1992, metal stents were inserted in 28 patients with malignant bile duct strictures secondary to ampullary tumour (n = 10), pancreatic carcinoma (n = 10), cholangiocarcinoma (n = 7), and porta hepatis nodes from colorectal carcinoma (n = 1). The follow up of these patients until May 1993 is reported with a median follow up of 14.6 months. Twenty two of 28 (78.6%) patients remained free of jaundice or cholangitis. The median period of stent patency was 8.2 months (range 1.0-32.5). Thirteen patients represented with jaundice or cholangitis and endoscopic retrograde cholangiopancreatography showed evidence of stent occlusion due to tumour ingrowth. Successful clearance of metal stents was achieved by balloon trawling, or insertion of a polyethylene stent. In conclusion, metal stents provide improved longterm palliation for patients with malignant biliary strictures with fewer episodes of occlusion compared with conventional stents.

https://gut.bmj.com/content/gutjnl/36/4/618.full.pdf

A three year follow up of self expanding metal stents in the endoscopic palliation of longterm survivors with malignant biliary obstruction.

The aim of this study was to clarify the mechanism by which cytochrome P450 (P450)-mediated catalytic activity is decreased following interferon (IFN) administration. Microsomal steroid hydroxylation was assessed to test the hypothesis that IFN selectively decreases the activities of individual P450 isozymes in male rats. Thus, recombinant rat IFN gamma (r-rat IFN gamma) treatment produced 40% and 17% reductions in androst-4-ene-3,17-dione (androstenedione) 6 beta- and 16 beta-hydroxylation, respectively. Androstenedione 16 alpha- and 7 alpha-hydroxylation were unaltered following r-rat IFN gamma treatment. Similar changes in the androstenedione hydroxylation pathways were observed following administration of naturally derived rat IFN alpha/beta. Microsomal levels of P450IIIA2, the male-specific constitutive steroid 6 beta-hydroxylase, were lower after administration of r-rat IFN gamma (42% of control fractions). Furthermore, hepatic P450IIIA2 mRNA was found to be decreased to a similar extent by r-rat IFN gamma. These findings suggest that IFN selectively decreases the content of this isozyme by a mechanism involving altered mRNA regulation. Sex steroids were unlikely to have mediated the decrease in P450IIIA2 levels since serum estradiol and testosterone levels were unchanged by r-rat IFN gamma. In order to determine whether IFN alters the expression of P450IIIA1, a steroid-inducible member of the P450IIIA gene subfamily which is not expressed in untreated rat liver, adult female rats (which lack P450IIIA2) were coadministered pregnenolone 16 alpha-carbonitrile and r-rat IFN gamma. However, IFN failed to impair the induction of androstenedione 6 beta-hydroxylation produced by pregnenolone 16 alpha-carbonitrile. These findings suggest that although IFN decreases the expression of P450IIIA2, it may not down regulate the expression of other steroid-inducible P450IIIA proteins. In view of the existence of human P450IIIA orthologs which catalyze the metabolism of several important therapeutic agents, the findings of this study may help predict possible drug interactions in patients receiving IFN.

Interferon down regulates the male-specific cytochrome P450IIIA2 in rat liver.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840170212

Interferon suppresses erythromycin metabolism in rats and human subjects

Endoscopic therapy for upper-GI vascular ectasias



Twenty-one of 40 patients with chronic non-A, non-B hepatitis (37 anti-HCV positive) were randomised to receive interferon α2b (3 million units subcutaneously thrice weekly for 24 weeks) and then to be observed for six months. Among the other 19 patients (controls) randomised to be observed without treatment for 12 months, eight have subsequently been treated with interferon for six months. One treated patient and three controls were lost to follow-up. A return to normal serum alanine aminotransferase levels which lasted until the end of the treatment period occurred in 18 (64%) of the 28 patients given interferon (and in 13 of 21 (62%) randomised to treatment), but only in one of the 16 untreated controls (p < 0.001). Multivariant analysis indicated that, compared with the ten nonresponders, the 18 patients who responded to interferon were more likely to have acquired infection by intravenous drug abuse than by blood transfusion (p < 0.05), and were more likely to have histologically less severe chronic liver disease (p < 0.01). Thus, all 13 patients with less severe liver disease histologically responded to interferon, but only five of 15 patients with cirrhosis or bridging fibrosis responded. Among 17 responders followed for more than four months, five (28%) are still in remission a median of 13 months (range four months to 24 months) after stopping interferon. The characteristics which favoured a response during treatment also appeared to distinguish those who experienced sustained post-treatment remission. Thus, five of 12 patients with less severe chronic hepatitis C histologically appear to have a sustained remission of disease activity after treatment for six months with interferon, whereas none of five patients with cirrhosis or bridging fibrosis has had a sustained remission after interferon treatment. It is proposed that continued treatment with interferon may be required for long-term suppression of chronic active hepatitis C among patients with bridging fibrosis or cirrhosis, but one course of interferon may provide a lasting response in 40% of patients with less severe disease.

Philip I. Craig

Papers

A three year follow up of self expanding metal stents in the endoscopic palliation of longterm survivors with malignant biliary obstruction.

Interferon down regulates the male-specific cytochrome P450IIIA2 in rat liver.

Interferon suppresses erythromycin metabolism in rats and human subjects

Endoscopic therapy for upper-GI vascular ectasias

Can the response to interferon treatment be predicted in patients with chronic active hepatitis C