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BACKGROUND: Acute hepatitis C virus (HCV) infection is often asymptomatic; thus, its epidemiology and natural history are difficult to define. METHODS: Acute HCV infection was identified on the basis of HCV seroconversion within 1 year (n=45), new anti-HCV seropositivity with clinical acute hepatitis (n=21), or HCV strain sequencing after an iatrogenic exposure (n=1). Risk factors were assessed with a baseline questionnaire, and participants were followed up prospectively with serial measurement of viral loads. RESULTS: Of 67 persons with acute HCV infection, most were asymptomatic (64%) and injection drug users (66%). Thirteen had an unknown mode of transmission; of these, 11 reported high-risk sexual behavior. Ten acquired acute HCV infection within 3 months of an iatrogenic exposure; 3 had confirmed iatrogenic infection, and 4 had no other risk factors identified. The spontaneous viral clearance rate after 6 months of infection was 18% (95% confidence interval, 11%-31%). The rate of viral clearance varied significantly by sex (34% vs. 3% for women vs. men; P<.001). CONCLUSIONS: High-risk sexual or iatrogenic exposures may be important contemporary risk factors for HCV infection. The spontaneous viral clearance rate (18%) in this contemporary study was similar to that reported for past studies of transfusion-associated HCV infection. Women were more likely to clear acute HCV infection than men. [ABSTRACT FROM AUTHOR]

Background & Aims: Patients with end-stage liver disease (ESLD) have progressively complex medical needs. However, little is known about their end-of-life health care utilization or associated costs. We performed a population-based study to evaluate the end-of-life direct utilization and costs for patients with ESLD among health care sectors in the province of Ontario., Methods: We used linked Ontario health administrative databases to conduct a population-based retrospective cohort study of all decedents from April 1, 2010, through March 31, 2013. Patients with ESLD were compared with patients without ESLD with regard to total health care utilization and costs in the last year and last 90 days of life., Results: The median age at death was significantly lower for ESLD decedents (65 y; interquartile range, 56-75 y) than for individuals without ESLD (80 y; interquartile range, 68-88 y). The median cost in the last year of life was significantly greater for patients with ESLD ($51,235 vs $44,456 without ESLD) (P < .001). Median ESLD end-of-life care costs also significantly exceeded those associated with 4 of the 5 most resource-intensive chronic conditions ($69,040 for ESLD vs $59,088 for non-ESLD) (P < .001). Cost differences were most pronounced in the final 90 days of life. During this period, patients with ESLD spent 4.7 more days in the hospital (95% CI, 4.3-5.1 d) than patients without ESLD (P < .0001), had significantly higher odds of dying in an institutional setting (odds ratio, 1.8; 95% CI, 1.7-1.9) (P < .0001), and incurred an additional $4201 in costs (95% CI, $3384-$5019; P < .0001)., Conclusions: In a population-based study in Canada, we found that patients with ESLD incur significantly higher end-of-life care costs than decedents without ESLD, predominantly owing to increased time in the hospital during the final 90 days of life., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background. Treatment options are limited for patients with refractory cirrhotic ascites (RCA). As such, we assessed the safety and effectiveness of the PleurX catheter for RCA. Methods. A retrospective analysis was performed on all patients with RCA who have undergone insertion of the PleurX catheter between 2007 and 2014 at our clinic. Results. Thirty-three patients with RCA were included in the study; 4 patients were lost to follow-up. All patients were still symptomatic despite bimonthly large volume paracentesis and were not candidates for TIPS or PV shunt. Technical success was achieved in 100% of patients. The median duration the catheter remained in situ was 117.5 days, with 95% CI of 48-182 days. Drain patency was maintained in 90% of patients. Microorganisms consistent with spontaneous bacterial peritonitis (SBP) from a catheter source were isolated in 38% of patients. The median time to infection was 105 days, with 95% CI of 34-233 days. All patients were treated for SBP successfully with antibiotics. Conclusion. Use of the PleurX catheter for the management of RCA carries a high risk for infection when the catheter remains in situ for more than 3 months but has an excellent patency rate and did not result in significant renal injury.

Goals: To assess the current practice patterns of liver transplant centres in Canada and the USA regarding transplant eligibility., Background: Liver transplantation is an evolving field and today remains the only life-sustaining treatment for end-stage liver disease. Issues of allocation and transplant eligibility are important factors in the ethical practice of medicine., Study: Questionnaires were mailed to liver transplant programme directors in Canada and the USA inquiring about current practices regarding recipient eligibility., Results: This study demonstrates that there is consensus in the use of other eligibility criteria, including non-compliance, social status, abstinence from alcohol and methadone and cocaine use. Interestingly, literature is lacking to support the use of these parameters as eligibility criteria with the exception of alcohol. There is a lack in consensus regarding marijuana use, human immunodeficiency virus status, ability to accept blood transfusions and prisoner status. The literature suggests that liver transplantation in select patients who refuse blood transfusions results in good outcomes., Conclusions: Important decisions regarding transplant eligibility still have to be made empirically in the absence of scientific literature about various social issues. While consensus among transplant programmes is useful, it is important that we continue to use the evidence in the literature to revise these eligibility criteria, keeping in mind ethical principles applied to the access and allocation of a scarce resource.

In an attempt to more completely define the histopathologic features of the portal vein hyperperfusion or small-for-size syndrome (PHP/SFSS), we strictly identified 5 PHP/SFSS cases among 39 (5/39; 13%) adult living donor liver transplants (ALDLT) completed between 11/01 and 09/03. Living donor segments consisting of 3 right lobes, 1 left lobe, and 1 left lateral segment, with a mean allograft-to-recipient weight ratio (GRWR) of 1.0 +/- 0.3 (range 0.6 to 1.4), were transplanted without complications, initially, into 6 relatively healthy 25 to 63-year-old recipients. However, all recipients developed otherwise unexplained jaundice, coagulopathy, and ascites within 5 days after transplantation. Examination of sequential posttransplant biopsies and 3 failed allografts with clinicopathologic correlation was used in an attempt to reconstruct the sequence of events. Early findings included: (1) portal hyperperfusion resulting in portal vein and periportal sinusoidal endothelial denudation and focal hemorrhage into the portal tract connective tissue, which dissected into the periportal hepatic parenchyma when severe; and (2) poor hepatic arterial flow and vasospasm, which in severe cases, led to functional dearterialization, ischemic cholangitis, and parenchymal infarcts. Late sequelae in grafts surviving the initial events included small portal vein branch thrombosis with occasional luminal obliteration or recanalization, nodular regenerative hyperplasia, and biliary strictures. These findings suggest that portal hyperperfusion, venous pathology, and the arterial buffer response importantly contribute to early and late clinical and histopathologic manifestations of the small-for-size syndrome.

Budd-Chiari syndrome (BCS) is a rare but potentially life-threatening disorder caused by hepatic venous obstruction, distinct from cardiac causes of hepatic congestion or sinusoidal obstruction syndrome (formerly known as veno-occlusive disease). BCS may be classified as primary or secondary, depending on the underlying process. Most cases of primary BCS are due to an underlying hypercoagulable disorder. A high index of suspicion is required to make the diagnosis. In most case series, chronic, indolent cases of BCS are more common than acute presentations. Doppler ultrasound, magnetic resonance imaging (MRI), and direct venography are useful in confirming the diagnosis. Systemic anticoagulation should be started expeditiously, as long as there are no contraindications. The use of systemic thrombolysis remains controversial. However, thrombolysis may prove effective when it is administered locally following hepatic venoplasty with or without stenting. Guidelines for the management of more complex cases and of patients who fail medical management are currently in evolution. Budd-Chiari syndrome (BCS) is potentially life-threatening, depending on the extent and rapidity of hepatic venous obstruction. A high index of suspicion is required to clinch the diagnosis, since BCS may be quite indolent or even asymptomatic. Doppler ultrasound or magnetic resonance imaging (MRI) is usually definitive. Systemic anticoagulation should be offered to all patients, unless contraindicated. The role of thrombolysis in BCS remains controversial, and thus it should be reserved for cases undergoing hepatic decompression via percutaneous angioplasty. Guidelines for the management of cases who fail standard medical management are currently in evolution.

The search for continues for a safe, accurate and reliable method to quantify liver function similar in principle to renal creatinine clearance or pulmonary function spirometry tests. When evaluating patients in the more advanced stages of chronic liver disease, one's clinical judgement regarding the degree of liver dysfunction usually suffices, but in patients with early or only intermediate disease, and estimate based on routine blood tests and/or clinical severity scores is often unreliable. A more quantitative approach under investigation at present has been to monitor specific pharmacokinetic parameters of 'probe' drugs metabolized primarily by hepatic cytochrome P-450. These parameters include the plasma or salivary clearance rate of the parent compound and/or the formation rate of its metabolites. Following a review of basic hepatic pharmacology relevant to this topic, we shall explore the advantages and disadvantages of two 'metabolic probes' that have shown the most promise to date, caffeine and lidocaine.

Henoch-Schönlein purpura is a common vasculitic syndrome of childhood that is also seen in adults. It is characterized by the deposition of immune complexes, mainly IgA and C3, in various organ systems. Diagnosis is based on the presence of nonthrombocytopenic purpura, arthritis or arthralgia, abdominal pain that may be complicated by intussusception, and glomerulonephritis. The disease is usually self-limited and lasts a few weeks but may recur. Recovery is complete in almost all patients, with the severity of renal involvement dictating any remaining sequelae. Corticosteroid therapy may provide acute symptomatic relief but apparently has no effect on the natural course of the disease.

Objectives: Plasma cholecystokinin increases with enteral feeding. Cholecystokinin increases intracellular calcium in lymphocytes/monocytes and is a lymphocyte co-mitogen. We hypothesize that decreased cholecystokinin production with "bowel rest" and parenteral nutrition may be beneficial in inflammatory bowel disease by down-regulating gut immune/inflammatory mechanisms. The majority of cells observed in mucosa of inflammatory bowel disease are monocytes and neutrophils. Cholecystokinin effect was therefore measured on monocyte production of proinflammatory mediators (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6) and neutrophil chemotaxins/activators (interleukin-8, granulocyte-macrophage colony stimulating factor, and leukotriene B4)., Methods: Peripheral blood monocytes (0.5 x 10(6)) from healthy donors in 1 mL of RPMI 1640 plus 5% fetal calf serum were cultured for 24 h in 5% CO2 at 37 degrees C with 5 micrograms/mL endotoxin, 1 x 10(-7) M cholecystokinin, or no agonist. Supernatants were analyzed by ELISA for cytokines and leukotriene B4., Results: Endotoxin-stimulated monocytes produced 1130 pg/mL tumor necrosis factor versus 81 pg/mL for cholecystokinin, 612 pg/mL interleukin-1 versus 10 pg/mL, 694 pg/mL interleukin-6 versus 30 pg/mL, 4531 pg/mL of interleukin-8 versus 3848 pg/mL, 21 pg/mL granulocyte-macrophage colony stimulating factor versus 9 pg/mL, and 21 pg/mL leukotriene B4 versus 12 pg/mL. Controls produced no cytokines/eicosanoids (N = 8, p < 0.001)., Conclusion: Cholecystokinin increase with enteral feeding may up-regulate gut immune response. Cholecystokinin suppression with parenteral alimentation may decrease inflammatory mediator production.

Sjögren's syndrome (SS) is an autoimmune exocrinopathy that primarily affects the salivary glands but can also involve almost any other part of the gut. The most distressing manifestation of SS is xerostomia secondary to destruction of the salivary glands. The lack of saliva also leads to difficulty with chewing and initial swallowing and an increased frequency of dental caries. Another major problem is dysphagia due to the lack of saliva as well as esophageal dysmotility and/or esophageal webs. Chronic atrophic gastritis probably accounts for the epigastric pain, nausea, and other dyspeptic symptoms seen in SS. Sjögren's syndrome is also one of the most frequent extrahepatic diseases associated with primary biliary cirrhosis, suggesting that this entity may be a secondary form of SS. The degree to which SS affects the small and large bowel is unclear, whereas pancreatic involvement appears to lead to only subclinical exocrine insufficiency.

Objectives: The pharmacokinetic and pharmacodynamic interactions after 7 days of oral treatment with nisoldipine (10 mg twice daily) and propranolol (80 mg twice daily) were investigated in a partially randomized, placebo-controlled crossover study of 12 healthy volunteers., Methods: At the end of each treatment period, pharmacokinetic parameters were measured, along with blood pressure, heart rate, cardiac function, systemic hemodynamics, plasma catecholamines, forearm blood flow, and apparent hepatic blood flow (estimated by the clearance of indocyanine green dye)., Results: After 7 days of treatment with nisoldipine and propranolol, neither drug altered the other's bioavailability or elimination parameters, and propranolol did not change the area under the plasma concentration-time curve of nisoldipine's metabolite, N-9425. Nisoldipine alone increased apparent hepatic blood flow and forearm blood flow compared with the other treatment groups but, with the addition of propranolol, both of these parameters were similar to those in the placebo group. Changes in the other hemodynamic parameters were consistent with the known effects of these drugs, and no differences in plasma catecholamine levels were detected., Conclusions: In contrast to the findings with single-dose treatment, administration of the combination of nisoldipine and propranolol for 7 days is not associated with any measurable kinetic interactions, although significant hemodynamic interactions do occur.

PEM or the possibility of developing PEM occurs in 30% to 50% of hospitalized patients, the frequency determined by the criteria used in its assessment and the case mix of patients in the hospital population. This condition exists independently of other medical conditions and results from preadmission or postadmission failure to meet nutrient requirements with associated loss of body weight and function, as well as impaired immunity. PEM also frequently arises in patients with a chronic condition and decreased functional reserve when a superimposed acute metabolic stress leads to accelerated nutrient depletion. Whether preexisting or not, PEM increases morbidity and mortality along with LOS and may be associated with complications such as pneumonia, sepsis, operative site infection, delayed wound healing, or decubitus ulcers. The cost of these complications and an extended LOS is a significant financial burden and a controllable medical liability for hospitals. Other costs include identifying patients at risk of PEM, providing nutrition support, not to mention treating any of its complications (mechanical, metabolic, and so forth). A proper analysis of the financial implications of late or untreated PEM versus nutrition support must therefore take into account not only the costs of complications or extended LOS due to the delay or failure to provide nutrition support but also the costs associated with this intervention itself. In this review, we described a model for examining the financial implications of malnutrition and nutritional therapy.

Various factors may prolong postoperative recovery and the length of stay (LOS) in the hospital. In a retrospective study of 245 adult patients who had no oral intake for 5 days after major gastrointestinal surgery, we used a correlation matrix to describe the population and determine the effects of the following factors on LOS: malnutrition, complication status, stress level, type of surgery, pathology, period of inadequate nutrient intake, and use of nutritional support. LOS was markedly prolonged in malnourished patients compared with those who were not (23.5 +/- 16.5 vs. 16.5 +/- 10.7 days, means +/- SD, p < 0.001). Patients were then grouped into those who had nutritional support and those who had not, and a nutrition classification was derived by examining the uncertainty (entropy) in the data matrix that allowed separation of the population into distinct groups. Nutrition and complication status and days without oral nutrient intake were discriminative. Analysis of variance and multivariate studies were also used to determine whether the presence of malnutrition, complications, both together, or neither could predict LOS and to determine the confounding effect of nutritional support on LOS. A significantly extended LOS persisted for patients with malnutrition or complications and was most prolonged for those with both, but patients who received nutritional support had a greater LOS than those who did not. In addition to the effects of nutritional support, malnutrition, and complication status, LOS correlated with the duration of the postoperative period without oral nutrient intake. We therefore recommend systematic and early nutritional intervention for selected gastrointestinal surgical patients.

To assess the role of renal prostaglandin E2 in the pathogenesis of refractory ascites, in relation to renal sodium handling and circulating levels of vasoconstrictive substances, we studied 12 cirrhotic patients with refractory ascites before and after peritoneovenous shunting. Baseline values for urinary prostaglandin E2 excretion, sodium excretion, and creatinine clearance, as well as serum aldosterone, plasma renin activity, and plasma free norepinephrine, were obtained preoperatively with patients on a sodium- and fluid-restricted diet. Diuretics were also withheld. Similar parameters were measured immediately postoperatively during four consecutive 2-h intervals, then again at 2 wk and 3 mo. In patients with refractory ascites, mean baseline urinary prostaglandin E2 excretion was significantly elevated (2.5 +/- 0.8 pmol/min), compared with that in both normal controls and cirrhotics without ascites (1.3 +/- 0.3 pmol/min). A significant natriuresis occurred immediately postoperatively and persisted at 2 wk and 3 mo. Concomitantly, the elevated levels of preoperative vasoconstrictor substances gradually normalized by 2 wk. Urinary prostaglandin E2 excretion, however, rose transiently in the immediate postoperative period and then fell gradually to within the normal range by 3 mo. Enhanced renal prostaglandin E2 synthesis, therefore, does not play a role in the sustained improvement in sodium homeostasis after peritoneovenous shunting in patients with refractory ascites.