Penelope Jones

Early detection of protein depletion in alcoholic cirrhosis : role of body composition analysis

BACKGROUND Malnutrition is common in alcoholic cirrhosis. Bedside nutritional assessment techniques may be unreliable in patients with chronic liver disease. The aim of this study was to quantify changes in body composition and compare methods for measuring body composition in alcoholic cirrhosis. METHODS Thirty-eight men with alcoholic cirrhosis were compared with 16 age-matched healthy men. Body composition was assessed using anthropometry and bioelectrical impedance to determine fat-free mass and body fat, deuterium oxide dilution to measure total body water, in vivo neutron activation analysis to measure total body protein, and dual energy x-ray absorptiometry to measure bone mineral content and total body fat mass. RESULTS With increasing severity of cirrhosis, total body water increased, whereas total body protein decreased with a significant decrease in serum albumin levels. Total body protein levels, expressed as an index, were a more sensitive indicator of protein depletion than serum albumin levels. When patients were assessed by anthropometry and bioelectrical impedance for fat-free mass, there was no reduction compared with controls. CONCLUSIONS Anthropometry and bioelectrical impedance do not accurately reflect changes in body composition associated with chronic liver disease. Quantification of body composition changes in alcoholic cirrhosis requires the use of direct methods such as in vivo neutron activation analysis, dual energy x-ray absorptiometry, or deuterium oxide dilution.

Increased Sympathetic Nervous Activity and the Effects of Its Inhibition with Clonidine in Alcoholic Cirrhosis

OBJECTIVE To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of clonidine on such disturbances. DESIGN Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous clonidine in the cirrhotic patients. PATIENTS Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls. INTERVENTIONS Intravenous clonidine. MAIN OUTCOME MEASURES Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function. MAIN RESULTS In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% CI, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; CI, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; CI, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 micrograms/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation. CONCLUSIONS The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis.

Splenectomy Associated Changes in IgM Memory B Cells in an Adult Spleen Registry Cohort

Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001) reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

Primary hepatic lymphoma in a patient with chronic hepatitis C

The case is presented of a woman with chronic active hepatitis C who developed primary hepatic lymphoma. The possible roles of viral hepatitis and therapeutic interferon in the pathogenesis and progression of this unusual maligancy are discussed. In addition, the importance of accurate tissue diagnosis to identify potentially treatable hepatic tumours is emphasized.

Change in serum hyaluronan: A simple index of short-term drug-induced changes in hepatic sinusoidal perfusion

BACKGROUND Hyaluronan is an endogenous polysaccharide whose clearance from the plasma is predominantly by liver sinusoidal cells and is sinusoidal flow dependent. This study was designed to determine if a change in serum hyaluronan might reliably reflect short-term drug-induced changes in sinusoidal perfusion. METHODS Hemodynamic changes following an oral dose of ketanserin were compared with changes in serum hyaluronan levels in 12 patients with alcoholic liver disease and portal hypertension. Indices determined comprised heart rate, mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance, hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and extraction, and total hepatic blood flow. Measurements were made in a basal state 1 hour after ketanserin ingestion and expressed as a ratio of values post- to pre-ketanserin administration. RESULTS Ketanserin had variable effects comprising both increases and decreases in all indices. On univariate and multivariate analysis, changes in serum hyaluronan concentration (1.05 +/- 0.13, mean +/- SD) significantly correlated with only one index: changes in ICG clearance (0.93 +/- 0.17, r = -0.65, P = 0.02). CONCLUSIONS Changes in serum hyaluronan levels reflect short-term drug-induced changes in sinusoidal perfusion in patients with alcoholic liver disease and portal hypertension. Serial measurement of serum hyaluronan levels may offer a simple method of screening vasoactive drugs for their short-term effects on sinusoidal perfusion.

Cost‐effectiveness of a post‐splenectomy registry for prevention of sepsis in the asplenic

Background: Overwhelming, sometimes fatal infections represent a lifelong risk after surgical removal of the spleen, or in patients who develop hyposplenism as a consequence of illnesses. This risk may be reduced by all or a combination of vaccination, antibiotic prophylaxis and education. We aimed to determine if a registry approach to delivering these interventions would be cost effective using our own experience and published data.

Adherence to infection prevention measures in a statewide spleen registry.

Objective: To assess self‐reported adherence to measures for preventing infection in patients registered in the Victorian Spleen Registry (VSR).

A comparison of Doppler flowmetry with conventional assessment of acute changes in hepatic blood flow

The validity and clinical relevance of Doppler flowmetry in measuring changes in regional blood flow are uncertain. In the present study we compared changes induced by ketanserin in regional splanchnic blood flow as measured by Doppler flowmetry with changes in conventionally measured systemic and in hepatic haemodynamic indices estimated pharmacokinetically using indocyanine green. Fourteen patients with alcoholic cirrhosis and portal hypertension were evaluated. On multivariate analyses, significant associations were noted for only three indices: changes in estimated hepatic blood flow were predicted jointly by changes in flow in the main and right portal veins and hepatic artery (R2= 0.80); changes in intrahepatic shunting (indocyanine green extraction) were predicted by changes in flow in the main and right portal veins (R2= 0.55); and changes in sinusoidal perfusion (indocyanine green clearance) were significantly predicted by changes in main portal vein flow alone (R2= 0.76). These data support the validity of Doppler flowmetry in quantifying change in regional blood flow, but highlight the limitations in its clinical application and interpretation. The association of changes in main portal vein flow with changes in sinusoidal perfusion has clinical potential but requires confirmation using other modulating drugs.

Overwhelming post-splenectomy sepsis in patients with asplenia and hyposplenia: a retrospective cohort study

Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia and is associated with encapsulated organisms, most commonly Streptococcus pneumoniae, but also Haemophilus influenzae and Neisseria meningitidis. We aimed to estimate the risk of infection in this patient group. We reviewed data collected by the Victorian Spleen Registry in Australia. On registration, all patients are asked about significant infections requiring admission to hospital for intravenous antibiotics; those requiring admission to ICU were defined as OPSI. In the 3274 asplenic patients registered 492 patients reported at least one episode of infection. There were 47 episodes of OPSI requiring intensive care (incidence rate 1·11/1000 patient-years). The risk of OPSI was highest in older patients, and there were no statistically significant differences in incidence by reason for splenectomy except for a higher rate in patients with medical hyposplenia. This study reinforces that post-splenectomy infection is a clinically significant but uncommon complication, and that fulminant infection requiring intensive care is a minority of all infections.

Spleen Australia guidelines for the prevention of sepsis in patients with asplenia and hyposplenism in Australia and New Zealand

People with asplenia/hyposplenism are at increased risk of fulminant sepsis, which carries a high mortality rate. A range of preventive measures is recommended although there is ongoing evidence that knowledge of and adherence to these strategies is poor. There have been significant changes in recommended vaccinations since the previously published recommendations in 2008. We provide current recommendations to help Australian and New Zealand clinicians in the prevention of sepsis in patients with asplenia and hyposplenia. The guideline includes Australian epidemiological data, preferred diagnostic techniques and recommendations for optimal antimicrobial prophylaxis and vaccination protocols.