Hepatobiliary Complications in Critically Ill Patients.
Clinics in liver disease
2019; 23 (2): 221–32
Defining Improvement in Nonalcoholic Steatohepatitis for Treatment Trial Endpoints: Recommendations from the Liver Forum.
Hepatology (Baltimore, Md.)
Critically ill patients frequently present with the systemic inflammatory response syndrome, which is largely a reflection of the liver's response to injury. Underlying hepatic congestion is a major risk factor for hypoxic liver injury, the most common cause for hepatocellular injury. Cholestatic liver injury often occurs in critically ill patients due to inhibition of farnesoid X receptor (FXR), the main regulator of bile acid handling, particularly in the liver and intestines. Additional injury to the liver occurs due to alterations in the bile acid pool with increased cytotoxic forms and disturbance in the typical processing of xenobiotics in the liver.
View details for PubMedID 30947873
Nonalcoholic Fatty Liver Disease: Identification and Management of High-Risk Patients.
The American journal of gastroenterology
Identifying effective therapies for nonalcoholic steatohepatitis (NASH) with fibrosis is a pressing challenge, with 1-2% of the population in developed nations at risk of developing NASH cirrhosis and its complications. The design of NASH clinical therapeutic trials is hampered by the long period of minimally symptomatic disease that typically precedes the development of decompensated cirrhosis, and the accompanying uncertainties regarding the best pre-cirrhotic trial endpoints that reliably reflect a subsequent reduction in liver-related morbidity and mortality. The Liver Forum is a multi-stakeholder organization comprised of academic, industry, and regulatory experts working from a regulatory science perspective to identify barriers, prioritize research, and identify solutions to accelerate therapeutic development for NASH. Prior work of The Liver Forum has focused on recommendations for disease definitions and baseline parameters to be implemented in clinical trials that are designed to assess disease status and prevent progression to cirrhosis, liver transplantation, hepatocellular carcinoma, and death. The purpose of this summary is to review currently available clinical data to identify parameters that change in parallel with liver histology and are likely to reflect clinically meaningful reductions in the risk of developing cirrhosis and its complications. We review available data on exploratory histologic, blood-based and imaging pharmacodynamic biomarkers that may reflect meaningful treatment responses and provide recommendations regarding measurements to be considered in phase 2 and 3 trials as well as during post-marketing monitoring trials. This article is protected by copyright. All rights reserved.
View details for PubMedID 31034092
Infectious Complications in Critically Ill Liver Failure Patients.
Seminars in respiratory and critical care medicine
2018; 39 (5): 578–87
Nonalcoholic fatty liver disease (NAFLD) is an increasingly dominant cause of liver disease worldwide. The progressive subtype, nonalcoholic steatohepatitis, is a leading indication for liver transplantation and a noteworthy cause of hepatocellular carcinoma. The overall prevalence of NAFLD is on the rise, and even more concerning data modeling predicts that an increasing percentage of those with NAFLD will develop advanced disease. This increased volume of patients with advanced liver disease will impose a significant health care burden in terms of resources and cost. Thus, the identification of patients with established fibrosis or at high risk of developing advanced liver disease is critical to effectively intervene and prevent overall and liver-related morbidity and mortality. Herein, we provide a framework to consider for the identification of patients with NAFLD at high risk of nonalcoholic steatohepatitis with advanced fibrosis and provide a critical assessment of currently accessible diagnostic and treatment modalities.
View details for PubMedID 30839326
Follow-up of the Post-Liver Transplantation Patient: A Primer for the Practicing Gastroenterologist.
Clinics in liver disease
2017; 21 (4): 793–813
Infections remain a leading cause of morbidity and mortality among patients with liver failure. A number of factors, including relative immune dysfunction and systemic inflammation, bacterial translocation, gut dysbiosis, small intestine bacterial overgrowth, altered bile acid pools, and changes in pH due to acid suppression, contribute to the high rates of infection in this population. Though a range of infections can complicate the course of cirrhotic patients, spontaneous bacterial peritonitis (SBP), cholangitis, and cholecystitis in addition to other infections (i.e. pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile colitis) are more common in this population and will be reviewed in this article. Preventative strategies are directed at minimizing the risk of SBP through the use of targeted antimicrobial prophylaxis. Lastly, the critically ill cirrhotic patient may present with an acute need for liver transplantation. Thus, careful assessment for ongoing infection should be performed and treated to optimize outcomes of transplant, if needed.
View details for DOI 10.1055/s-0038-1673657
View details for PubMedID 30485888
Diarrhea Concealing a Duodenal-Cecal Fistula Secondary to Appendiceal Mucinous Neoplasm.
ACG case reports journal
The focus in liver transplantation in the next 10 years will likely change from preventing viral disease recurrence to minimizing the toll of rejection and fatty liver disease, minimizing the complications from immunosuppression with withdrawal strategies, and more optimal management of long-term risks, such as malignancy, cardiovascular disease, and renal failure. In addition, now that short-term results (<1 year) have improved significantly, there will be a shift toward improving long-term patient and graft survival, as well as a focus on primary care preventive strategies.
View details for DOI 10.1016/j.cld.2017.06.006
View details for PubMedID 28987263
Idiopathic hypereosinophilic syndrome presenting with hepatitis and achalasia.
Clinical journal of gastroenterology
2016; 9 (4): 238-242
Primary mucinous adenocarcinoma of the appendix is a rare gastrointestinal malignancy. Fistulous tract formation is a complication that is cited in literature. An 85-year-old man with multiple comorbidities presented with several weeks of persistent non-bloody diarrhea. Laboratory work-up was non-diagnostic. Abdominal imaging with barium contrast showed an enterocolonic fistulous tract extending from the duodenum to the cecum involving an enlarged appendiceal mass. Subsequent biopsy confirmed mucinous appendiceal neoplasm with peritoneal spread to the liver and mesentery. This is the first report describing an enterocolonic fistula formation resulting from this malignancy.
View details for DOI 10.14309/crj.2017.3
View details for PubMedID 28138447
View details for PubMedCentralID PMC5244891
Presurgical Transarterial Chemoembolization Does Not Increase Binary Stricture Incidence in Orthotopic Liver Transplant Patients
2014; 46 (5): 1413-1419
Idiopathic hypereosinophilic syndrome (HES) is a rare diagnosis defined by the World Health Organization as a persistent eosinophilia for 6 months and resulting in end-organ dysfunction. While many patients present with nonspecific symptoms, others will present with symptoms of the affected organs, most commonly those involving the heart, skin, or nervous system. Gastrointestinal or liver involvement is estimated to affect up to one-third of patients with HES, although patients with clinically significant disease are limited to case reports. This is the first report of a patient presenting with hepatitis and achalasia related to idiopathic HES.
View details for DOI 10.1007/s12328-016-0661-8
View details for PubMedID 27294613
The goal of this study was to compare the incidence of biliary strictures in orthotopic liver transplant (OLT) patients treated with previous transarterial chemoembolization (TACE) versus those with no TACE history.A single-center retrospective review was performed on 248 patients who underwent OLT from 2006 to 2012. Patient demographic characteristics, history of TACE for treatment of hepatocellular carcinoma, OLT data, and biliary stricture data were obtained. TACE was generally performed in a segmental manner using chemotherapy to ethiodized oil mixture (1:1). Clinically significant biliary strictures resulting in cholestasis or obstructive jaundice were diagnosed by using endoscopic retrograde cholangiopancreatography. Group characteristics were compared by using the Wilcoxon rank sum test, χ(2) analysis, and Kaplan-Meier statistics with log-rank comparison.Forty-six patients (35 men, 11 women; median age, 58 years) with a history of pre-OLT TACE were compared with 185 patients (111 men, 74 women; median age, 54 years) with no history of TACE. TACE and non-TACE patients had 30% and 31% cumulative incidence of biliary stricture, respectively. The median time to stricture was not reached in either group. There was no statistically significant difference in biliary stricture incidence (P = .928) or time to biliary stricture development (P = .803). Biliary strictures were primarily anastomotic in location in both groups: 79% in TACE patients and 84% in non-TACE patients (P = .233).Selective TACE treatment of hepatocellular carcinoma in pretransplant patients does not increase the rate of posttransplant biliary strictures. These findings corroborate the safety of TACE in the treatment of hepatocellular carcinoma in potential OLT patients as a bridge to transplantation.
View details for DOI 10.1016/j.transproceed.2014.03.012
View details for Web of Science ID 000338090600026
View details for PubMedID 24935306