Tony Bruns

Adverse effects of biologics used for treating IBD

In the last decade, biologic agents, in particular anti-TNF agents such as infliximab, adalimumab, and certolizumab have substantially extended the therapeutic armamentarium of inflammatory bowel disease (IBD). Additional approaches include biologicals, such as natalizumab, that block leucocyte adhesion; those that target cytokines, such as interleukin-12/23 antibodies; or those that inhibit T-cell signaling, such as interleukin-6 receptor antibodies. However, these drugs have a number of contraindications and side effects, especially when used in combination with classical immunosuppressive agents or corticosteroids. Areas of concern include opportunistic infections, malignancies, and miscellaneous complications such as injection/infusion reactions and autoimmunity and contraindications, such as heart failure and acute infectious diseases. In this review, the indications of biologicals in IBD treatment are briefly reported, and the potential disadvantages of a more active therapeutic approach in IBD are discussed. We have learned in the last decade that anti-TNF-alpha therapy is an effective and relatively safe treatment option for selected patients that changes the natural course of severe IBD. However, despite these changed therapeutic paradigms and goals in IBD, clinicians should be aware that the powerful immunosuppressive capacity of biologicals necessitates a rigorous long-term safety follow-up.

Etiologies and Outcomes of Acute Liver Failure in Germany

BACKGROUND & AIMS Acute liver failure (ALF) is a severe form of acute liver injury that can progress to multiple organ failure. We investigated causes and outcomes of ALF. METHODS Eleven university medical centers in Germany were asked to report patients with (primary) severe acute liver injury (sALI) (international normalized ratio [INR] >1.5 but no hepatic encephalopathy) and primary ALF (INR >1.5 with overt hepatic encephalopathy) treated from 2008 to 2009. Data were analyzed from 46 patients with sALI and 109 patients with ALF. RESULTS The most frequent etiologies of primary ALF were non-acetaminophen drug-induced (32%), indeterminate (24%), and viral (21%); acetaminophen ingestion was the cause of ALF in only 9% of patients. The support of a ventilator was required by 44% of patients with ALF, vasopressors by 38%, and renal replacement by 36%. Seventy-nine patients with ALF (72%) survived until hospital discharge, 38 (35%) survived without emergency liver transplantation (ELT), and 51 received ELT (47%); 80% of patients who received ELT survived until discharge from the hospital. CONCLUSIONS In Germany, drug toxicity, indeterminate etiology, and viral hepatitis appear to be the major causes of primary ALF, which has high mortality. Patients with ALF are at great risk of progressing to multiple organ failure, but 80% of patients who receive ELT survive until discharge from the hospital.

NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis.

Background: Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.

Identification of bacterial DNA in neutrocytic and non-neutrocytic cirrhotic ascites by means of a multiplex polymerase chain reaction

Background: Even though bacterial cultures of ascitic fluid are negative in up to 65% of the cases of spontaneous bacterial peritonitis (SBP); bacterial DNA (bactDNA) has been frequently detected in episodes of SBP as well as in culture‐negative non‐neutrocytic ascites.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease – a prospective multicenter observational study

Vedolizumab, a monoclonal antibody targeting the α4β7‐integrin, is effective in inducing and maintaining clinical remission in Crohns disease and ulcerative colitis according to randomised clinical trials.

Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response

BACKGROUND & AIMS Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events. METHODS We evaluated a cohort of PBC patients (n=386) attending the Liver Unit in Birmingham (derivation cohort), seeking to identify risk-variables associated with transplant-free survival independent of UDCA-response. A validation cohort was provided through well-characterised patients attending the Toronto Center for Liver Diseases (n=479) and Jena University Hospital (n=150). RESULTS On multivariate analysis, factors at diagnosis associated with liver transplant (LT)/death were patient age (HR:1.06; p<0.001), elevated bilirubin (HR:1.27; p<0.001), early-onset cirrhosis (HR:2.40; p<0.001) and baseline AST/platelet ratio index (APRI) (HR:1.95; p<0.001). At 1-year, UDCA biochemical non-response predicted poorer transplant-free survival, and additional factors (multivariate) associated with adverse outcome were age (HR:1.02; p<0.05) and 1-year APRI (HR:1.15; p<0.001). Obtaining a cut-point from our derivation cohort, APRI >0.54 at baseline was predictive of LT/death (adjusted HR: 2.40; p<0.001), and retained statistical significance when applied at 1-year (APRI-r1, adjusted HR:2.75; p<0.001) despite controlling for UDCA-response. Across both cohorts, transplant-free survival was poorer for biochemical-responders with an APRI-r1 >0.54 vs. biochemical-responders with a lower APRI-r1 (p<0.01 and p<0.001, respectively); non-responders with high APRI-r1 had the poorest outcomes (p<0.001 and p<0.001). CONCLUSION In PBC, elevated APRI is associated with future risk of adverse events, independently and additively of UDCA-response. This cross-centre, robustly validated observation will contribute to ongoing efforts to refine existing risk-stratification tools, as well as direct focus for new therapies in patients with PBC.

Risk factors and outcome of bacterial infections in cirrhosis

Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating infections and organ failure in advanced cirrhosis. Bacterial infections and sepsis are now recognized as a distinct stage in the natural progression of chronic liver disease as they accelerate organ failure and contribute to the high mortality observed in decompensated cirrhosis. The increasing knowledge of structural, immunological and hemodynamic pathophysiology in advanced cirrhosis has not yet translated into significantly improved outcomes of bacterial infections over the last decades. Therefore, early identification of patients at the highest risk for developing infections and infection-related complications is required to tailor the currently available measures of surveillance, prophylaxis and therapy to the patients in need in order to improve the detrimental outcome of bacterial infections in cirrhosis.

Medical and surgical therapy of inflammatory bowel disease in the elderly — Prospects and complications

Population ageing is a global phenomenon. People aged 65 years and older comprise approximately 16% of the population of Europe. The medical management of elderly patients with inflammatory bowel disease (IBD) is challenging with respect to diagnosis, pharmaceutical and surgical treatment, and complications. IBD has a late onset in 10%-15% of patients, with the first flare occurring at 60 to 70 years of age; others suffer from the disease for several decades. Even though the natural course of the disease in geriatric populations and the diagnostic options may not differ much from those in younger patients, distinct problems exist in the choice of medical therapy. Recommended clinical practise has been rapidly evolving towards an intensified initial treatment in IBD. However, in patients older than 65 years, a gentler approach should be used, and a combination of immunosuppressive agents should be avoided because of increased risk of infectious and neoplastic complications. Furthermore, elderly patients with severe IBD show prolonged, complicated post-operative clinical courses with worse hospital outcomes, so early surgical intervention for elderly patients is recommended. This article provides an overview of elderly IBD patient care, including medical and surgical therapeutic considerations and emphasises the necessity of close collaborations between gastroenterologists and surgeons.

Effects of Antibiotics on Gut Microbiota.

The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease.

Emergence of spontaneous bacterial peritonitis due to enterococci – risk factors and outcome in a 12-year retrospective study

Third‐generation cephalosporins (TGC) constitute the empirical first‐line therapy for spontaneous bacterial peritonitis (SBP). Hospitalisation, invasive procedures and use of antibiotics may challenge this concept due to an increase in enterococci and other TGC‐resistant microorganisms.