Stephen E. Congly

Portal Vein Thrombosis: Should Anticoagulation Be Used?

Portal vein thrombosis (PVT) can contribute to significant morbidity and mortality; in patients with cirrhosis, this can make transplant more technically challenging. Additionally, the clot may extend further into the mesenteric and splenic veins, and disturbance of the hepatic blood flow may lead to faster progression of the cirrhosis. Development of PVT is associated with local risk factors, and many patients have associated systemic prothrombotic factors. Anticoagulation in noncirrhotic patients should be initiated at diagnosis, using low-molecular-weight heparin overlapping with vitamin K antagonists. Cirrhotic patients with PVT should be screened for varices and then anticoagulated with low-molecular-weight heparin for at least a 6-month period. All patients should be assessed for triggering factors and tumors, as well as systemic prothrombotic factors. Newer evidence suggests that prophylactic anticoagulation in patients with cirrhosis may have a role in clinical management with decreased incidence of PVT and improved survival; further study is needed.

Amoebic liver abscess in USA: a population-based study of incidence, temporal trends and mortality.

Background: Amoebic liver abscess (ALA) may be associated with significant morbidity and mortality, but nationwide American data is unavailable. Our objective was to describe ALA epidemiology and outcomes in USA from a population‐based perspective.

Characterization of hepatitis B virus genotypes and quantitative hepatitis B surface antigen titres in North American tertiary referral liver centres.

Hepatitis B virus (HBV) genotype and quantitative hepatitis B surface antigen (qHBsAg) have been related to clinical outcome. In this nationwide cross‐sectional study, we aimed to investigate the epidemiology and clinical significance of HBV genotype and qHBsAg in patients with chronic hepatitis B (CHB).

Hepatitis B immunoglobulin for prevention of hepatitis B virus infection and recurrence after liver transplantation

Intravenous hepatitis B immunoglobulin (HBIG) is a human plasma-derived purified gammaglobulin (IgG) that has proven efficacy and dose-dependent response in the prevention of hepatitis B virus (HBV) recurrence after liver transplantation. It is also indicated for postexposure prophylaxis after contact with blood or body fluids of serum hepatitis B surface antigen (HBsAg)-positive carriers and in prevention of mother-to-child (vertical) transmission. The exact mechanism of passive immunization is unknown; HBIG may block HBV entry and binding to hepatocytes, neutralize circulating HBV and target HBV-infected cells through an antibody-mediated immune response. The drug is well tolerated and common side effects include fever, chills and arthralgias that are usually mild and transient. This article summarizes the main indications and the recommendations for use of intravenous HBIG, as well as the usage of intramuscular HBIG in the liver transplant setting.

Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B carriers

Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first‐line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown.

Cost effectiveness of quantitative hepatitis B virus surface antigen testing in pregnancy in predicting vertical transmission risk.

Vertical transmission of hepatitis B virus (HBV) can occur despite immunoprophylaxis in mothers with high HBV DNA levels (>5–7 log10 IU/ml). Quantitative hepatitis B surface antigen (qHBsAg) testing could be used as a surrogate marker to identify high viral load carriers, but there is limited data in pregnancy. We conducted a prospective observational study to determine the cost‐effectiveness and utility of qHBsAg as a valid surrogate marker of HBV DNA.

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus (HIV) positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers. Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients co-infected with hepatitis B virus (HBV). However, liver transplantation in HIV positive patients with hepatitis C virus (HCV) has poorer outcomes overall, requiring careful selection of candidates. This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management. In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.

Prediction of bleeding etiology: the clinician is vindicated!

Gastrointestinal (GI) bleeding is associated with significant morbidity and mortality. Variceal bleeds are significantly more life-threatening than nonvariceal bleeds, with mortality rates of 18% in variceal bleeds (1) versus 5% in nonvariceal bleeds (2). Determining the acuity of the bleed is important to ensure that therapeutic upper endoscopy is performed within a window of time that balances mortality risk against optimal use of a limited resource. Several prediction scores have been proposed to risk stratify patients with upper GI bleeds, including the Rockford and Blatchford scales (3,4). These scores are, however, limited because they do not discriminate between GI bleeds of variceal and nonvariceal origin. This is a crucial distinction because management is different. In the current issue of the Canadian Journal of Gastroenterology, Alharbi et al (5) (pages 187–192) investigate preprocedure characteristics of patients ultimately diagnosed with variceal and nonvariceal upper GI bleeds. The patients were enrolled in the REgistry of patients undergoing endoscopic and/or Acid Suppression therapy and Outcomes analysis for upper gastrointestinal bleediNg (REASON) trial, with an aim to identify patient characteristics that distinguish variceal bleeds from nonvariceal bleeds. This multicentre, Canadian study conducted over an 18-month period found 11% of upper GI hemorrhages to be secondary to varices, which is similar to the rate found in the United Kingdom (6). Thirty-day mortality rates were significant for non-variceal bleeds (9.4%) and 14.4% for variceal bleeds. After multivariate analysis, statistically significant risk factors associated with a variceal bleed included a history of liver disease, the presence of any stigmata of liver disease, alcohol abuse, hematemesis and hematochezia. This study also provides a unique snapshot of the management of GI bleeds in a very large geographical area. While outcome comparisons among centres were not reported, as a whole, mortality figures were similar to those reported in other western societies. Somewhat surprisingly, in 42% of cases, a rectal examination appeared not to be performed. In 19% of cases, a fecal occult blood test from a stool sample was performed – a test that has no utility in the context of an upper GI bleed (however, these fecal occult blood tests may have been performed by nongastroenterologists). Given that definitive management of variceal and nonvariceal upper GI bleeds is different, as are the transfusion goals and adjunct therapy (albumin and antibiotics in variceal bleeding), better methodology to discriminate variceal from nonvariceal bleeding has the potential to improve patient outcomes through earlier recognition. Previous work has investigated predictive factors of who will experience poor outcomes with a GI bleed (ie, the Rockford and Blatchford scales). These scales have been validated in real-world populations of patients presenting with both variceal and nonvariceal bleeding (3,4). An extension of this concept is to predict which patients are likely to experience variceal bleeds before a potentially life-threatening bleeding episode. This includes measuring liver stiffness through transient elastography (7) and biochemical parameters such as a platelet to spleen ratio (8,9). Unfortunately, a diagnosis of cirrhosis is often made at the time of a variceal bleed, limiting the utility of these techniques, and emphasizing a need for a high index of suspicion for the presence of high-risk varices in outpatient populations. It would be of clinical relevance to incorporate the significant findings of the study by Alharbi et al in an outpatient model of at-risk patients who have yet to experience a variceal bleed. Two single-centre trials from Thailand have also studied how to differentiate nonvariceal bleeds from variceal GI bleeds. Pongprasobchai et al (10) found an 18% incidence of variceal bleeding in their study, which is higher than the rate found by the REASON investigators. Factors supporting a variceal source include a history of cirrhosis, signs of chronic liver disease, hematemesis and blood from a nasogastric aspirate. Further support was found in the recent study by Rattanasupar (11), which confirmed the predictive value of signs and symptoms of chronic liver disease, as well as a history of cirrhosis. Interestingly, the type of emesis did not appear to be predictive; rather, a low hematocrit of <30% was found to have a significant association with varices. In combination, this study found that all three tests had a specificity of 98.2%, but a poor sensitivity of 59.5%. The best test characteristics were found with clinical signs of chronic liver disease. It is difficult to extrapolate these findings to the Canadian population given the different demographics of the Thai population and a likely higher proportion of patients with cirrhosis due to viral causes (hepatitis B in particular). The study by Alharbi et al provides us with the largest series investigating a mixed population of patients presenting with upper GI hemorrhage. It confirms some preprocedure patient characteristics that can predict a greater likelihood of GI bleeding due to varices. While consistent, these characteristics are not terribly surprising; however, an important take home message is to have a high index of suspicion for a variceal source of bleeding in patients with a known history of cirrhosis or with clinical signs of chronic liver disease. Overall, the study by Alharbi et al vindicates bedside examination, confirming that clinical clues, obtained through history and physical examination, can accurately predict which patients are likely to experience upper GI bleeding due to varices. These factors in the clinical assessment should be used in addition to using risk prediction scores such as the Rockford or Blatchford scale. Further validation of predictive factors in a prospective trial, as well as in other countries, might help in the development of a clinical predictive scoring system to be used in combination with history and physical examination.

Cost-Effectiveness of Early Insertion of Transjugular Intrahepatic Portosystemic Shunts for Recurrent Ascites

Background & Aims Treatment options for recurrent ascites resulting from decompensated cirrhosis include serial large‐volume paracentesis and albumin infusion (LVP+A) or insertion of a transjugular intrahepatic portosystemic shunt (TIPS). Insertion of TIPSs with covered stents during early stages of ascites (early TIPS, defined as 2 LVPs within the past 3 weeks and <6 LVPs in the prior 3 months) significantly improves chances of survival and reduces complications of cirrhosis compared with LVP+A. However, it is not clear if TIPS insertion is cost effective in these patients. Methods We developed a Markov model using the payer perspective for a hypothetical cohort of patients with cirrhosis with recurrent ascites receiving early TIPSs or LVP+A using data from publications and national databases collected from 2012 to 2018. Projected outcomes included quality‐adjusted life‐year (QALY), costs (2017 US dollars), and incremental cost‐effectiveness ratios (ICERs;

Long-Term Follow-up and Quantitative Hepatitis B Surface Antigen Monitoring in North American Chronic HBV Carriers

/QALY). Sensitivity analyses (1‐way, 2‐way, and probabilistic) were conducted. ICERs less than