Daphna Fenyves

Value of measurement of mean portal flow velocity by Doppler flowmetry in the diagnosis of portal hypertension

To establish the sensitivity and specificity of the mean portal flow velocity in the diagnosis of portal hypertension, a population of 304 consecutive cirrhotic patients, in whom 246 abdominal Doppler examinations were performed, was prospectively analysed between June 1988 and December 1990. To avoid equipment-related variability only examinations performed using the same equipment were considered. Further inclusion criteria were the absence of portal vein thrombosis or reversed flow in the portal vessels and the absence of spontaneous, ultrasonographically detectable, portosystemic shunts. The parameter evaluated was mean portal flow velocity calculated directly from the Doppler trace by specific, operator-independent, software. 123 patients satisfied the inclusion criteria. As a control group 60 healthy age- and sex-matched subjects were examined. Mean portal flow velocity was significantly lower in cirrhotic patients than healthy subjects (13.0 +/- 3.2 cm/s vs. 19.6 +/- 2.6 cm/s; p < 0.001). There was also a decrease in mean portal flow velocity in cirrhotics in each Child-Pugh category (13.8 +/- 2.8 cm/s in Child-Pugh A class; 12.1 +/- 3.5 cm/s in Child-Pugh B class and 11.0 +/- 2.4 cm/s in Child-Pugh C class) with a statistically significant difference between each Child-Pugh category and healthy subjects (p < 0.001), between Child-Pugh A and B (p < 0.01) and between Child-Pugh A and C (p < 0.005). The sensitivity and specificity of mean portal flow velocity in the detection of portal hypertension was then analyzed with the receiver operating characteristic curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of chronic bleeding from gastric antral vascular ectasia (GAVE) with estrogen-progesterone in cirrhotic patients: an open pilot study.

Objective:Gastric antral vascular ectasia (GAVE) is a rare cause of chronic bleeding in cirrhotic patients. Treatment of GAVE with surgical or nonsurgical portal decompression, β-blockers, or endoscopic therapy provides disappointing results. In the present study, we evaluated the efficacy of estrogen-progesterone therapy, which has been reported to control chronic bleeding in gastrointestinal vascular malformations, such as Osler-Weber Rendu disease or angiodysplasia, in GAVE-related chronic bleeding.Methods:Six cirrhotic patients who bled chronically from GAVE were included. Three had alcoholic cirrhosis, two cryptogenic cirrhosis, and one primary biliary cirrhosis. Grade 1 esophageal varices were noted in four patients. Bleeding could not be controlled by β-blockers, and endoscopic therapy was not considered given the extension of the antral vascular lesions.Results:Before the start of therapy, transfusion requirements averaged 3.5 units/month over a 1.5–11 month period of observation. Patients were then treated with a combination of ethynil estradiol 30 μg and noretisterone 1.5 mg daily. During follow-up (range 3–12 months), bleeding did not recur in four patients; in one patient, treatment with estrogen progesterone decreased the need for transfusions from 4 units/month to 1.4 unit/month; this patient stopped the treatment inadvertently after 6 months and severe anemia recurred with a need for 4 units of blood in the following month; reintroduction of the treatment resulted in an increase of hemoglobin levels without the need for blood transfusions during the following 4 months. In the last patient, a 5-month treatment did not improve chronic bleeding.Conclusion:The present study suggests that estrogen-progesterone therapy is useful in the treatment of chronic bleeding related to GAVE; however, these findings require confirmation by a controlled trial.

Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec.

BACKGROUND Hepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency, MIM 276700) can cause severe hepatic, renal and peripheral nerve damage. In Québec, HT1 is frequent and neonatal HT1 screening is practiced. Nitisinone (NTBC, Orfadin ®) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone and has been offered to HT1 patients in Québec since 1994. METHODS We recorded the clinical course of 78 Québec HT1 patients born between 1984 and 2004. There were three groups: those who never received nitisinone (28 patients), those who were first treated after 1 month of age (26 patients) and those treated before 1 month (24 patients). Retrospective chart review was performed for events before 1994, when nitisinone treatment began, and prospective data collection thereafter. FINDINGS No hospitalizations for acute complications of HT1 occurred during 5731 months of nitisinone treatment, versus 184 during 1312 months without treatment (p<0.001). Liver transplantation was performed in 20 non-nitisinone-treated patients (71%) at a median age of 26 months, versus 7 late-treated patients (26%, p<0.001), and no early-treated patient (p<0.001). No early-treated patient has developed detectable liver disease after more than 5 years. Ten deaths occurred in non-nitisinone treated patients versus two in treated patients (p<0.01). Both of the latter deaths were from complications of transplantation unrelated to HT1. One probable nitisinone-related event occurred, transient corneal crystals with photophobia. INTERPRETATION Nitisinone treatment abolishes the acute complications of HT1. Some patients with established liver disease before nitisinone treatment eventually require hepatic transplantation. Patients who receive nitisinone treatment before 1 month had no detectable liver disease after more than 5 years.

Predictors of clinical response to transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with refractory ascites

Objective:Transjugular intrahepatic portosystemic shunt (TIPS) is used increasingly as a treatment for refractory ascites. The aim of the present study was to determine the prognostic value of different parameters in predicting a favorable evolution following TIPS in a cohort of 53 cirrhotic patients without organic renal disease and with refractory ascites.Methods:Patients were classified as good responders if they survived more than 6 months, without severe chronic hepatic encephalopathy and with good control of ascites. The prognostic value for a good outcome was evaluated using age, creatinine clearance, plasma renin activity, plasma aldosterone, and Pugh score.Results:Good control of ascites was obtained in 90%. The cumulative survival rate was 54% at 6 months, 48% at 1 yr, and 39% at 2 yr. The vast majority of patients died of complications of hepatic insufficiency. Severe chronic hepatic encephalopathy developed in 26%. Overall, a good clinical response was observed in 47%. Creatinine clearance was identified as the only pre-TIPS factor to be significantly and independently associated with a good clinical response to TIPS for refractory ascites. A good clinical response was observed in 57% of patients with a creatinine clearance >36 ml/min compared to 9% of those with a clearance <36 ml/min p < 0.01. This cutoff point in creatinine clearance had a sensitivity of 96% and a specificity of 36%; positive predictive and negative predictive values were 57% and 90%, respectively.Conclusions:TIPS might be useful for the treatment of refractory ascites in cirrhotic patients without severe renal function impairment. However, the TIPS usefulness still has to be demonstrated compared to large volume paracentesis or Leveen shunt. In patients with poor renal function or with liver failure after TIPS, liver transplantation should be considered.

Treatment of refractory ascites using transjugular intrahepatic portosystemic shunt (TIPS) : A caution

Ascites becomes refractory to medical treatmentin nearly 10% of cirrhotic patients, who then requirerepeated large-volume paracentesis. In this prospectivestudy we evaluated the use of transjugular intrahepatic portosystemic shunt (TIPS) in 30 patients withrefractory ascites. TIPS was successful in all andresulted in a 54% reduction in portacaval gradient (from22.8 ± 0.8 to 10.4 ± 0.6 mm Hg). Ascitesbecame easily controlled with diuretics in 26 patientsfollowing TIPS. Ascites recurrence associated with shuntstenosis was observed during follow-up in eightpatients; revision could be undertaken in five of themand resulted in good control of ascites. Inresponders, a marked decrease in plasma aldosterone andrenin activity, a reduction in serum creatinine, and arise in urinary sodium excretion were observed.Creatinine and inulin clearances improved significantly;PAH clearance remained unchanged. However, new-onset orworsening hepatic encephalopathy was seen in 14patients. Severe disabling chronic encephalopathyoccurred in five patients; it could be reversedsuccessfully by balloon occlusion of the shunt in three.The cumulative survival rate was 41 and 34% at 1 and 2years, respectively. In summary, TIPS can controlrefractory ascites in a majority of patients but isassociated with a high rate of chronic disabling HE. Inaddition, the survival rate is poor. Randomized trialsare needed to evaluate the exact role of TIPS in the management of refractory ascites. It isunlikely to improve survival but can ameliorate qualityof life in nontransplant candidates and be useful as abridge to transplantation, in particular, to improve denutrition associated with longstanding tenseascites.

Changes in plasma endothelin-1 and Big endothelin-1 induced by transjugular intrahepatic portosystemic shunts in patients with cirrhosis and refractory ascites

BACKGROUND/AIMS Endothelin-1 (ET-1) is a potent vasoconstrictor that may be involved in the pathogenesis of splanchnic and renal hemodynamic changes associated with portal hypertension. The aim of this study was to measure the concentration of ET-1 and of its precursor Big endothelin-1 (Big ET-1) in the systemic circulation as well as in the splanchnic and renal venous beds and to evaluate changes after the relief of portal hypertension following transjugular intrahepatic portosystemic shunt placement. METHODS Plasma concentrations of ET-1 and of Big ET-1 were measured in the vena cava, renal vein, hepatic vein and portal vein in ten patients with cirrhosis and refractory ascites before and 1-2 months after transjugular intrahepatic portosystemic shunt. The porto-caval gradient, creatinine clearance, plasma aldosterone and renin activity, as well as daily urinary sodium excretion were measured at the same time. RESULTS The plasma concentration of ET-1 and Big ET-1, respectively, in peripheral blood of normal volunteers were 0.28 +/- 03 and 3.95 +/- 0.34 pg/ml; the concentrations of both peptides were higher in patients with cirrhosis, both in vena cava (0.61 +/- 0.14 and 10.01 +/- 1.47 pg/ml), hepatic vein (0.62 +/- 0.13 and 13.93 +/- 1.77 pg/ml), portal vein (1.21 +/- 0.12 and 17.84 +/- 1.98 pg/ml) and renal vein (0.76 +/- 0.12 and 14.21 +/- 1.55 pg/ml). Moreover ET-1 and Big ET-1 concentrations were more elevated in the portal vein than in the vena cava (+98% and +70%) and slightly higher in the renal vein as compared to the vena cava (+25% and +42%). After transjugular intrahepatic portosystemic shunt, a rise in creatinine clearance and urinary sodium excretion (+49%; and +53%) was observed together with a marked reduction in plasma aldosterone and renin activity (-59% and -49%). ET-1 and Big ET-1 concentrations remained unchanged in the vena cava whereas a significant reduction of ET-1 and Big ET-1 occurred both in the portal vein (-43% and -44%) and in the renal vein (-53% and -29%). Portal vein and renal vein concentrations of both peptides became similar to vena cava levels. CONCLUSIONS Splanchnic and renal hemodynamic changes occurring in patients with cirrhosis and refractory ascites could be related to the production of ET-1 by splanchnic and renal vascular beds. This was abolished by transjugular intrahepatic portosystemic shunt, which could explain the exacerbation of systemic vasodilation and the improvement in renal perfusion observed after the procedure.

Descriptive Epidemiology of Primary Biliary Cirrhosis in the Province of Quebec

Primary biliary cirrhosis (PBC) is a rare disease, but is usually recognized because of the characteristic clinical picture and the diagnostic specificity of antimitochondrial antibody (AMA) determination. Information on the epitlemiology of PBC is limited. The authors have examined the incidence and prevalence of PBC in the province of Quebec, where all short term hospitals are required to classify discharge summary diagnoses according to the International Classification of Diseases. Code 571.6 designates primary or secondary biliary cirrhosis. The authors reviewed the charts of all patients to whom this code was assigned during a six year period (1980-86). Two hundred and twenty-eight subjects satisfied predetermined diagnostic criteria for PBC. The mean annual incidence rate was 3.9 per 106 population, and the point prevalence in 1986 was 25.4 per 106 population. Ninety-two patients were female, with a mean age at the time of diagnosis of 55.7 years; 89.4% had positive AMA, and 10.5% were asymptomatic. As of January 1, 1989, 126 patients were alive, 91 had died, and 11 had undergone liver transplantation. Cumulative five and 10 year survivals from the time of initial diagnosis were 69% and 49%, respectively. In patients with serum bilirubins greater than 100 μmol/L (n=66), cumulative two year survival was 5.5%. These data indicate that the incidence and prevalence of PBC in Quebec arc similar to chose reported in Ontario and at the lower end of the range of chose reported in western Europe. The clinical features and evolution of PBC are also similar, and serum bilirubin is a major prognostic factor.

Transient healing of TIPS-induced biliovenous fistula by PTFE-covered stent graft

Transjugular intrahepatic portosystemic shunt (TIPS) is used increasingly to manage the complications of portal hypertension. Despite its low procedural mortality and morbidity, vascular structures, as well as bile ducts, can be injured during the technique. Hemobilia occurred in less than 10% of cases in one large series (1); it usually resolves spontaneously. Leakage of bile into the systemic venous circulation may occur after the accidental creation of a fistula between a bile duct and a vein, leading to bilhemia. There are very few reports in the literature of this complication and its management . We report the case of a patient who developed bilhemia following revision of TIPS and in whom this was successfully managed by transjugular insertion of a polytetrafluoroethylene (PTFE) -covered stent, which transiently sealed the presumed site of the fistula.

Cefotaxime, Desacetyl-Cefotaxime, and Bactericidal Activity in Spontaneous Bacterial Peritonitis

We have prospectively studied 13 episodes of spontaneous bacterial peritonitis (SBP) in 12 patients treated with cefotaxime (CTX) 2 g intravenously every 8 h (mean duration, 5.3 days). Ascitic fluid was inoculated at the bedside. The cultures were done before, during (day 3 after CTX initiation), and 48-72 h (mean, 56 h) after the end of therapy. All SBP episodes were monomicrobial. During treatment, the concentrations of CTX and desacetyl-cefotaxime (d-CTX) in ascitic fluid were high in all 13 SBP episodes, and d-CTX was still present in 6 patients who had residual ascitic bactericidal titer (ABT) activity after the last dose of CTX. ABTs were >/=1:128 during CTX therapy in 12 episodes and were measurable in 7 patients after the last dose. All patients were cured. The present study provides scientific rationale to the clinical studies that suggest treating SBP episodes with lower doses of antibiotics and shorter treatment duration.

Successful reversal of chronic incapacitating post-TIPS encephalopathy by balloon occlusion of the stent

Transjugular intrahepatic portosystemic shunt (TIPS) placement is a new technique allowing decompression of the portal system without the need for abdominal surgery or general anesthetic. This promising procedure appears safe, and is being evaluated in the context of life threatening uncontrollable variceal hemorrhage as well as ascites refractory to medical treatment. Following TIPS, portal flow diversion is associated with hepatic encephalopathy in up to 25% of patients. This is most often mild and treatable but may become uncontrollable, incapacitating and even life threatening in up to 3 to 5% of cases. The authors present two patients in whom such life threatening encephalopathy and stupor was reversed by transjugular balloon occlusion of the TIPS.