Alla Grigorian

Probiotic Mix VSL#3 Is Effective Adjunctive Therapy for Mild to Moderately Active Ulcerative Colitis: A Meta-analysis

Background:VSL#3 is a probiotic mix preparation reported to be effective in the treatment of mild to moderately active ulcerative colitis. We aimed to perform a systematic review of the literature and a meta-analysis of studies on its efficacy. Methods:The searched databases included PubMed, Scopus, and ScienceDirect. The Mantel–Haenszel method was used to pool the effect- ize across studies, and the odds ratios (ORs) and 95% confidence intervals (CIs) of experiencing a specific outcome were calculated. Results:Five studies with 441 patients were identified. The pooled remission rate was 49.4% (95% CI, 42.7–56.1). Only 3 low risk of bias studies with 319 patients met the inclusion criteria for further analysis. A total of 162 patients received 3.6 × 1012 CFU/d VSL#3, and 157 patients received placebo. A total of 95% of patients received concomitant therapies with 5-ASA and/or immunomodulators. The Ulcerative Colitis Disease Activity Index was used to define response and remission. A >50% decrease in the Ulcerative Colitis Disease Activity Index was achieved in 44.6% of the VSL#3-treated patients versus 25.1% of the patients given placebo (P = 0008; OR, 2.793; 95% CI, 1.375–5.676; number needed to treat = 4–5). The response rate was 53.4% in VSL#3-treated patients versus 29.3% in patients given placebo (P < 0001; OR, 3.03; 95% CI, 1.89–4.83; number needed to treat = 3–4). The remission rate was 43.8% in VSL#3-treated patients versus 24.8% in patients given placebo (P = 0007; OR, 2.4; 95% CI, 1.48–3.88; number needed to treat = 4–5). No serious side effects were reported. Conclusions:VSL#3, when added to conventional therapy at a daily dose of 3.6 × 1012 CFU/d, is safe and more effective than conventional therapy alone in achieving higher response and remission rates in mild to moderately active ulcerative colitis.

Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: A meta-analysis

BACKGROUND AND AIM Fenofibrate is a potential novel therapy for primary biliary cirrhosis (PBC). We performed a systematic review and a meta-analysis of studies of fenofibrate in PBC. METHODS Electronic database search was performed for relevant studies. A search of abstracts presented in the main scientific meetings in the field and articles in press was also performed. Random effect model was used to pool the effect size across studies for changes in alkaline phosphatase, GGT, bilirubin and IgM levels before and after treatment and the overall rate of complete response to fenofibrate therapy. RESULTS Six studies with 102 patients met the inclusion criteria. All studies were case series and in all, patients who had no or incomplete response to UDCA had fenofibrate added at a dose of 100-200mg daily. Treatment duration ranged from 8-100weeks. Treatment with fenofibrate was associated with a significant decrease in alkaline phosphatase (-114IU/L, 95% CI: -152 to -76, P<0.0001); a significant decrease in GGT level (-92IU/L, 95% CI: -149 to -43; P=0.0004); significant decrease in total bilirubin (-0.11mg/dL, 95% CI: -0.18 to -0.08; P=0.0008); and a significant decrease in IgM level (-88mg/dL, 95% CI: -119 to -58; P<0.0001). The complete response rate was 69% (95% CI: 53-82%) with an odds ratio of 82.8 (95% CI: 21.6-317.2; P=0.024) while on fenofibrate. CONCLUSIONS Fenofibrate at doses of 100-200mg daily appears to be effective adjunctive therapy in PBC patients who had no or incomplete response to UDCA. There is a critical need for larger scale randomized trials to determine its effect on liver-related morbidity and mortality (or progression towards end-stage disease).

Heart transplantation in cardiac amyloidosis

Abstract“Cardiac amyloidosis” is the term commonly used to reflect the deposition of abnormal protein amyloid in the heart. This process can result from several different forms, most commonly from light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, which in turn can represent wild-type (ATTRwt) or genetic form. Regardless of the origin, cardiac involvement is usually associated with poor prognosis, especially in AL amyloidosis. Although several treatment options, including chemotherapy, exist for different forms of the disease, cardiac transplantation is increasingly considered. However, high mortality on the transplantation list, typical for patients with amyloidosis, and suboptimal post-transplant outcomes are major issues. We are reviewing the literature and summarizing pros and cons of listing patients with amyloidosis for cardiac or combine organ transplant, appropriate work-up, and intermediate and long-term outcomes. Both AL and ATTR amyloidosis are included in this review.

Liver transplantation for fibrolamellar hepatocellular carcinoma: A national perspective

Fibrolamellar Hepatocellular Carcinoma (FL‐HCC) is a rare primary liver tumor that usually presents in younger patients without underlying liver disease.

The efficacy of endoscopic therapy for pancreas divisum: a meta-analysis

Background The purpose of this study was to perform a meta-analysis assessing the efficacy and predictors of success of endoscopic therapy in the management of patients with pancreas divisum. Methods An electronic database search (PubMed and ScienceDirect) was performed for relevant studies. Studies were selected based on predefined criteria and data were extracted on patient population, follow up, endotherapy methods, success rates and complication rates. A random-effect model was used to pool the effect size across studies. Heterogeneity testing and publication bias assessment were performed. Multivariate regression analysis was performed to identify predictors of successful endoscopic therapy. Results Of 381 articles reviewed, 23 studies with 874 patients met the inclusion criteria. All were case series with suboptimal quality. Endoscopic therapy included minor papilla sphincterotomy, minor papilla sphincteroplasty and dorsal duct stenting. Mean follow-up duration was 37 months. The rate of “improvement” as defined by authors after endoscopic therapy varied significantly across studies, ranging from 31-96%: 589/874 patients were reported to have improved, corresponding to a pooled efficacy rate of 67.5% (95% confidence interval [CI] 0.610-0.734; P=0.0001). The pooled rate of pancreatitis after endoscopic retrograde cholangiopancreatography was 10.1% (95%CI 0.084-0.124; 2-sided P=0.0001). On subgroup analysis, patients with recurrent acute pancreatitis had better endoscopic outcomes (pooled efficacy rate 76%, 95%CI 0.712-0.803, P=0.0001). Dorsal duct stenting and longer follow up were the only parameters predictive of successful endotherapy. Significant heterogeneity was observed within and across studies. Conclusions Endoscopic efficacy in pancreas divisum is estimated at 67.5%. Available studies are of poor quality with significant heterogeneity. Comparative studies with rigorous methodology are needed.

Successful Liver Transplantation From a Donor With a Continuous-Flow Left Ventricular Assist Device for 9 Months

Organ donor criteria continue to be extended in an attempt to meet growing demands. Patients with continuous-flow left ventricular assist devices are one group of potential donors being considered. One concern with this group is the effect of continuous flow for a prolonged duration, as opposed to normal pulsatile flow, on end-organ function. We report the 1st case of a liver transplantation from a donor who had a continuous-flow left ventricular assist device for 9 months. The recipient was a 69-year-old woman with a history of cryptogenic cirrhosis and hepatocellular carcinoma. The transplantation was complicated by moderate acute cellular rejection as well as biliary obstruction requiring sphincterotomy and stent placement. After management of those complications, the patients liver function tests returned to normal values and remained stable at her 6-month post-transplantation follow-up. This case shows that organ transplantation from a donor with a continuous-flow left ventricular assist device for a prolonged period can be performed successfully.

Liver Transplantation for the Treatment of Complicated Iatrogenic Biliary Injuries: A National Review from the UNOS Data Set

Background Liver transplantation (LT) is rarely indicated in the management of iatrogenic bile duct injuries (IBDI), but occasionally, it becomes the only remaining therapy. The purpose of this study is to evaluate potential complications of IBDI and their impact on perioperative mortality, graft, and patient survival after LT. Methods The United Network for Organ Sharing database was queried for all LT performed in the United States between 1994 and 2014. Of the 101 238 liver transplants performed, 61 were related to IBDI. We performed a case matched analysis in a 5:1 ratio. Results The median age for patients with IBDI was 50.16 ± 11.7 years with a mean Model End-Stage Liver Disease score of 22.6 ± 9.8. Patients receiving LT for IBDI were more likely women (54.1%, P = 0.001), had lower incidence of hepatitis C virus infection (4.9%, P = 0.001) and longer cold ischemic time (P = 0.001). The mean body mass index was 25.5 ± 5.2 in patients transplanted for IBDI. IBDI was recognized as the strongest independent predictor associated with eightfold increased risk of early graft loss (P = 0.001; odds ratio, 8.4) and a 2.9-fold increased risk of 30-day mortality after LT in a case matched analysis (P = 0.03). Conclusions IBDI is an uncommon but challenging indication for LT. These patients have significantly increased rates of early graft loss. IBDI is an independent factor related to increased risk of perioperative death after LT. Further studies are needed to determine the causes of perioperative complications and identify potential modifiable factors to improve outcomes in patients undergoing transplantation for IBDI.

Hepatic encephalopathy for the hospitalist

The care of patients with advanced liver disease is often complicated by episodes of acute decline in alertness and cognition, termed hepatic encephalopathy (HE). Hospitalists must be familiar with HE, as it is a common reason for hospitalization in this population and is associated with significantly increased mortality. This narrative review addresses common issues related to diagnosis and classification, precipitants, inpatient management, and transitions of care for patients with HE. The initial presentation can be variable, and HE remains a clinical diagnosis. The spectrum of HE manifestations spans from mild, subclinical cognitive deficits to overt coma. The West Haven scoring system is the most widely used classification system for HE. Various metabolic insults may precipitate HE, and providers must specifically seek to rule out infection and bleeding in cirrhotic patients presenting with altered cognition. This is consistent with the 4-pronged approach of the American Association for the Study of Liver Disease practice guidelines. Patients with HE are typically treated primarily with nonabsorbable disaccharide laxatives, often with adjunctive rifaximin. The evidence for these agents is discussed, and available support for other treatment options is presented. Management issues relevant to general hospitalists include those related to acute pain management, decisional capacity, and HE following transjugular intrahepatic portosystemic shunt placement. These issues are examined individually. Successfully transitioning patients recovering from HE to outpatient care requires open communication with multiple role players including patients, caregivers, and outpatient providers. Journal of Hospital Medicine 2016;11:591-594.

Probiotics in inflammatory bowel disease: is it fair to lump them into a one size that fits all?

To the Editor: We read with interest the metaanalysis by Shen et al on the use of probiotics in inflammatory bowel disease. We had a few concerns regarding the studies included in the analysis, particularly the subanalysis of VSL#3 in ulcerative colitis. First, the authors pooled data from markedly heterogeneous studies, as indicated by tests of heterogeneity. Pooling data from studies of various populations (adults and pediatrics) and studies that examined various doses and concomitant therapies increase the risk of obtaining inaccurate estimates. In their 2004 study, Tursi et al used “arbitrarily” defined outcomes and a lower dose of VSL#3 (900 billion CFU) than in their recent high quality study (3600 billion). Surprisingly (may be not), the results of the latter were less impressive with only 43% remission rate compared with 80% in the earlier study. Miele et al used a weight-based dose in pediatric patients who received concomitant systemic steroids as part of their induction regimen, and all patients in the study attained response, but remission rates were different. Remission rates among patients treated with VSL#3 ranged from 42% to 92%. Rates were lower in higher quality studies (40%–50%) and higher in studies with high-risk of bias (80%– 92%), which received more weight in the analysis when they should have been excluded. Second, meta-analyses are most conclusive and informative when they address a focused and specific question/ intervention in a population that is as homogeneous as possible. Probiotics have been defined as “living microorganisms, which on ingestion in certain numbers exert health benefits beyond inherent basic nutrition.” Although this definition is generic and lacks specificity, it stresses the importance of dose and diversity. An attempt to lump probiotics into a one size that fits all is impractical and yields results that can be difficult to interpret. This is reminiscent of attempts made to make conclusions about the use of antibiotics in inflammatory bowel disease from meta-analyses. Pooled analyses of antibiotic therapies showed statistically significant effect at inducing remission in active Crohn’s disease and ulcerative colitis, but the evidence was still considered a very low quality given the different antibiotic regimen evaluated and the presence of moderate heterogeneity between studies. Finally, we think that there are multiple study-name/outcome mismatch in Figure 3/1.6.3. For example, the results of the study by Miele are described as Ng, and of Tursi 2010 as Sood and so forth.