Hock Foong Lui

Ten years' follow-up of 472 patients following transjugular intrahepatic portosystemic stent-shunt insertion at a single centre.

Background Transjugular intrahepatic portosystemic stent-shunt (TIPSS) is increasingly used for the management of portal hypertension. We report on 10 years’ experience at a single centre. Methods Data held in a dedicated database was retrieved on 497 patients referred for TIPSS. The efficacy of TIPSS and its complications were assessed. Results Most patients were male (59.4%) with alcoholic liver disease (63.6%), and bleeding varices (86.8%). Technical success was achieved in 474 (95.4%) patients. A total of 13.4% of patients bled at portal pressure gradients ⩽ 12 mmHg, principally from gastric and ectopic varices. Procedure-related mortality was 1.2%. The mean follow-up period of surviving patients was 33.3 ± 1.9 months. Primary shunt patency rates were 45.4% and 26.0% at 1 and 2 years, respectively, while the overall secondary assisted patency rate was 72.2%. Variceal rebleeding rate was 13.7%, with all episodes occurring within 2 years of TIPSS insertion, and almost all due to shunt dysfunction. The overall mortality rate was 60.4%, mainly resulting from end-stage liver failure (42.5%). Patients who bled from gastric varices had lower mortality than those from oesophageal varices (53.9% versus 61.5%, P < 0.01). The overall rate of hepatic encephalopathy was 29.9% (de novo encephalopathy was 11.5%), with pre-TIPSS encephalopathy being an independent predicting variable. Refractory ascites responded to TIPSS in 72% of cases, although the incidence of encephalopathy was high in this group (36.0%). Conclusions TIPSS is effective in the management of variceal bleeding, and has a low complication rate. With surveillance, good patency can be achieved. Careful selection of patients is needed to reduce the encephalopathy rate.

Chronic administration of losartan, an angiotensin II receptor antagonist, is not effective in reducing portal pressure in patients with preascitic cirrhosis

OBJECTIVES:Plasma angiotensin II (ANG II) concentrations are elevated in cirrhosis and have been implicated as a cause of portal hypertension. We aimed to study both the systemic and portal hemodynamics, and tolerability after chronic administration of losartan, an ANG II receptor antagonist.METHODS:Twelve patients with preascitic cirrhosis were studied: mean age of 53.8 ± 3.3 yr; average Child-Pugh score of 5.8 ± 0.3; alcohol etiology (5), hepatitis B/C (1/3), primary biliary cirrhosis (3). No patients were on diuretics or vasoactive medication. Hemodynamic measurements were performed at baseline and 4 weeks after daily administration of 25 mg losartan.RESULTS:There was no significant change in the hepatic venous pressure gradient (15.4 ± 1.5 to 13.6 ± 1.6 mmHg, −11.7%, p= NS), despite a significant reduction in the wedge hepatic venous pressure (20.3 ± 1.8 to 17.3 ± 1.8 mmHg, −14.8%, p< 0.05). Cardiac output, hepatic blood flow, systemic vascular resistance, creatinine clearance, and natriuresis were unaffected. The plasma renin activity increased significantly from 2.7 ± 0.4 to 5.2 ± 1.1 ng/ml/h (p< 0.05). There was a significant reduction in the mean arterial pressure from 96.9 ± 3.3 to 89.3 ± 3.5 mmHg, −7.8 ± 3.0% (p= 0.02), with 1 patient experiencing symptomatic hypotension.CONCLUSIONS:Chronic administration of low-dose losartan does not lead to a significant reduction in the portal pressure gradient. Losartan is unlikely to be useful in the management of patients with early cirrhosis, who are at risk of variceal bleeding.

Impact of transjugular intrahepatic portosystemic stent-shunt for secondary prophylaxis of oesophageal variceal haemorrhage: a single-centre study over an 11-year period.

Aims The role of various treatments for variceal haemorrhage is currently being evaluated. The purpose of this study was to analyse the impact of the use of endoscopic variceal sclerotherapy (EVS), variceal band ligation (VBL) and transjugular intrahepatic portosystemic stent-shunt (TIPSS) for secondary prophylaxis on the outcome of cirrhotic patients with the first episode of variceal haemorrhage presenting to a single centre. Methods Between 1986 and 1996, data from 225 consecutive patients with the first episode of variceal haemorrhage were analysed. The modality of treatment for secondary prophylaxis between 1986 and 1991 was EVS (group I:n = 83; Child class C, 29%; mean follow-up 36 ± 3 months), between 1991 and 1993 VBL (group II:n = 56; Child class C, 38%; mean follow-up 24 ± 3 months), and between 1995 and 1996 TIPSS (group III:n = 86; Child class C, 60%; mean follow-up 17 ± 1 months). Half of the patients between 1993 and 1995 underwent VBL and the other half had TIPSS. Data regarding rebleeding, mortality and encephalopathy were analysed using the Kaplan–Meier method. Coxs proportional hazard regression was used to test the significance of prognostic factors. Results Seventy-five per cent of patients re-bled in group I, 40% in group II, and 16% in group III (P < 0.0001). Mortality was significantly lower in the patients with Child class C disease in group III patients compared with those in groups I and II (P < 0.02). TIPSS was associated independently with reduced early mortality and re-bleeding. Conclusion The results of this study suggest that TIPSS improves survival in patients with advanced liver disease and variceal haemorrhage, and should be considered for secondary prophylaxis in high-risk patients.

Hepatitis B reactivation in a patient receiving radiolabeled rituximab

Following the establishment of the chimeric anti-CD20 antibody, rituximab, for the treatment of CD20-positive non-Hodgkin’s lymphoma (NHL), it has now been shown that the radiolabeled monoclonal antibody results in higher complete and overall response rates than the non-labeled counterpart [1]. There are two approved radioimmunotherapy (RIT) agents for treatment of relapsed or refractory indolent NHL. The role of RIT earlier in the disease course, in different disease settings and in conjunction with other forms of therapy is being tested [2]. Hence, an increasing role of RIT as part of standard NHL treatment regimes is likely. We now present a patient who developed hepatitis B reactivation after receiving RIT. A 48-year-old Chinese female with chronic hepatitis B virus (HBV) infection was diagnosed with stage IV follicular lymphoma in May 1996 and treated with six cycles of cyclophosphamide, vincristine and prednisolone (CVP). She relapsed in June 1999 and progressed despite multiple lines of chemotherapy, including rituximab in June 2000 and three cycles of cyclophosphamide, doxorubicin and prednisolone (CHP) (March to May 2001). The latter was complicated by hepatitis B reactivation for which she received lamivudine (June 2001 to March 2002). On further progression, she was treated with iodine 131-labeled rituximab in May 2002, receiving 75 cGy total body dose. Table 1 shows the blood count trend before and after infusion of radiolabeled rituximab. Her pre-RIT transaminases were normal, HbsAg positive, HBeAg negative, anti-HBeAb positive and HBV DNA <0.7 MEq/ml serum (Bayer). She attained good partial remission of lymphoma with radiolabeled rituximab. Her HBV DNA remained undetectable on serial monthly assays up till and including August 2002. In September 2002, she developed hepatitis B reactivation-raised alanine transaminase (75 U/l) and aspartate transaminase (42 U/l), HBV DNA 40.6 MEq/ml, HBeAg negative and antiHBeAb positive. Lamivudine was started upon reactivation resulting in full recovery. The lymphoma, however, progressed 5 months post-RIT. Hepatitis B is endemic in South East Asia. Although the frequency of hepatitis B reactivation with use of rituximab is unknown, there have been several reported cases of fatal fulminant hepatic failure in patients who received rituximab concurrently with chemotherapy [3, 4]. This report shows that the use of radiolabeled monoclonal antibody as a single agent is sufficient to induce hepatitis B virus reactivation, albeit in a heavily pretreated patient. Interestingly, our patient developed hepatitis reactivation only with RIT and not with rituximab alone. This was likely due to the prolonged period of lymphopaenia and immune suppression (see Table 1). Detection and monitoring of chronic HBV infection is important in the use of RIT. Y. L. Soong . K. M. Lee . S. Li Er Loong (*) Department of Radiation Oncology, National Cancer Centre, 11 Hospital Drive, Singapore, Singapore, 169610 e-mail: trdlle@nccs.com.sg Tel.: +65-63214204 Fax: +65-62228675

Randomised controlled trial of long term portographic follow up versus variceal band ligation following transjugular intrahepatic portosystemic stent shunt for preventing oesophageal variceal rebleeding

Background/aims: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the prevention of variceal rebleeding but requires invasive portographic follow up. This randomised controlled trial aims to test the hypothesis that combining variceal band ligation (VBL) with TIPSS can obviate the need for long term TIPSS surveillance without compromising clinical efficacy, and can reduce the incidence of hepatic encephalopathy. Patients/methods: Patients who required TIPSS for the prevention of oesophageal variceal rebleeding were randomised to either TIPSS alone (n = 39, group 1) or TIPSS plus VBL (n = 40, group 2). In group 1, patients underwent long term TIPSS angiographic surveillance. In group 2, patients entered a banding programme with TIPSS surveillance only continued for up to one year. Results: There was a tendency to higher variceal rebleeding in group 2 although this did not reach statistical significance (8% v 15%; relative hazard 0.58; 95% confidence interval (CI) 0.15–2.33; p = 0.440). Mortality (47% v 40%; relative hazard 1.31; 95% CI 0.66–2.61; p = 0.434) was similar in the two groups. Hepatic encephalopathy was significantly less in group 2 (20% v 39%; relative hazard 2.63; 95% CI 1.11–6.25; p = 0.023). Hepatic encephalopathy was not statistically different after correcting for sex and portal pressure gradient (p = 0.136). Conclusions: TIPSS plus VBL without long term surveillance is effective in preventing oesophageal variceal rebleeding, and has the potential for low rates of encephalopathy. Therefore, VBL with short term TIPSS surveillance is a suitable alternative to long term TIPSS surveillance in the prevention of oesophageal variceal rebleeding.

Albumin dialysis in critically ill patients: use versus omission of intradialytic heparin.

Albumin liver dialysis using the Molecular Adsorbent Recirculating System (MARS) (Teraklin AG, Rostock, Germany) is used in severe acute liver failure (ALF). We hypothesized that intradialytic heparin worsens preexisting hemostatic defects without enhancing system longevity or therapeutic efficacy. This was a retrospective, single center study of 10 critically ill patients (M : F = 8:2; mean age 58.5 +/- 16.5 years old; Acute Physiology and Chronic Health Evaluation II 25.0 +/- 3.5) treated with 31 MARS sessions (intradialytically heparinized : nonheparinized = 18:13). Mortality in this cohort was 80%. All MARS circuits were primed with dilute heparinized saline before commencement. However, intradialytic, intermittent, bolus heparin was administered on an ad hoc basis with circuit saline flush where indicated. Acute renal replacement therapy was instituted where indicated. Average total intradialytic heparin used was 757 +/- 389 IU. Circuit pressures were stable with or without intradialytic heparin. Significant reductions in serum urea, creatinine, ammonia, and total bilirubin were achieved using intradialytically heparinized and nonheparinized MARS. Thrombocytopenia and elevated activated partial thromboplastin time (aPTT) were further deranged post-MARS for both circuit types, but significantly so in intradialytically heparinized MARS: pre- versus post-MARS aPTT (s) 57.8 +/- 17.6 versus 88.7 +/- 48.0, P = 0.011, and platelet count (x 10(3)/L) 102.9 +/- 61.1 versus 84.4 +/- 50.5; P = 0.009. The use of low dose, intradialytic heparin during MARS exacerbates preexisting severe coagulopathy and thrombocytopenia in patients with severe ALF without enhancing circuit function and longevity. However, the role and safety of heparinized saline prime need further investigation.

MARS therapy in critically ill patients with advanced malignancy: a clinical and technical report

Abstract  

Transjugular intrahepatic portosystemic stent-shunt insufficiency and the role of diabetes mellitus

Background/aims Maintenance of long-term patency of transjugular intrahepatic portosystemic stent-shunts (TIPSS) has proved problematic. Various prognostic variables have been assessed as predictors, but the role of diabetes mellitus, which induces vascular endothelial cell dysfunction, has not been assessed. Methods We analysed the records of 248 patients who underwent TIPSS between July 1991 and July 1997, followed-up through to August 1998. Patients with at least one shunt assessment by portography and available blood glucose levels were eligible (177 patients; median follow-up, 15.0 months). Fourteen patients had a pre-procedural diagnosis of diabetes (one insulin dependent, seven oral hypoglycaemic treated and six diet controlled). In another 14 patients, diabetes was diagnosed at TIPSS insertion, giving a 28/177 (15.8%) prevalence of diabetes in our patients. Fifty-nine patients were excluded from the final analysis (including five diabetics), as they either died or had early shunt insufficiency (within 1 month of stent placement), leaving 118 patients (including 23 diabetics) to be included in the final analysis. Results Mean age, sex distribution, median follow-up (months) and pre-shunt portal pressure gradient were comparable in the two groups (diabetics versus non-diabetics). Child–Pugh classes A and B were more common in the diabetic group (P < 0.01), and the mean inserted stent diameter was larger in the diabetic group (P < 0.05). The presence of diabetes was associated with a higher incidence of delayed shunt insufficiency (P = 0.02), but there was no evidence of an association between presence of diabetes and variceal haemorrhage post TIPSS. Kaplan–Meier analyses revealed earlier insufficiency in diabetic patients compared with those without diabetes (P = 0.04). Age, gender and presence of diabetes are included in the final logistic regression model. Individuals who have diabetes are more likely to experience shunt insufficiency independent of age and gender. Conclusions Diabetes mellitus is common in patients undergoing TIPSS and is associated independently with increased incidence of primary delayed shunt insufficiency.