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Aims: In Asian countries, transarterial chemoembolisation (TACE) has long been used for palliation of unresectable hepatocellular carcinoma (HCC) without strong evidence of improved survival or quality of life. In 2002, a survival benefi of TACE was shown in two randomised controlled trials in Europe and Hong Kong. The effectiveness of interventions fo HCC is influenced by geographical factors related to diverse patient characteristics and protocols. Therefore, the validation of TACE as palliative modality for unresectable HCC requires confirmation in diverse patient populations. The aim of the present study was to assess the effectiveness of TACE for HCC in a North American population., Materials and Methods: This was a single centre prospective cohort study. Child-Pugh A cirrhosis or better patients wit unresectable HCC and without radiological evidence of metastatic disease or segmental portal vein thrombosis wer assessed between November 2001 and May 2004. Of 54 patients who satisfied the inclusion criteria, 47 underwent 80 TACE sessions. Chemoembolisation was carried out using selective hepatic artery injection of 75 mg/m(2) doxorubicin and lipiodol followed by an injection of embolic particles when necessary. Repeat treatments were carried out at 2-3 month intervals for recurrent disease. The primary outcome was overall survival; secondary outcomes were morbidity and tumour response., Results: The survival probabilities at 1, 2 and 3 years were 76.6, 55.5 and 50%, respectively. At 6 months after the first intervention, 31% of patients had a partial response and 60% had stable disease by RECIST criteria. Minor adverse events occurred after 39% of TACEs and major adverse events after 20% of sessions, including two treatment-related deaths (4% of patients). One patient had complete cancer remission after undergoing three TACE treatments. Further progression of tumour growth was prevented in 91% of tumours at the 6 month point after the first TACE. At 3 months, serum levels of the tumour marker alpha-feto protein were significantly reduced in patients with elevated levels before TACE., Conclusions: The survival probabilities at 1 and 2 years after TACE were comparable with results in randomised studies from Europe and Asia. Most patients tolerated TACE well, but clinicians need to be aware that moderately severe sideeffects require close monitoring and prompt intervention.

Background & Aims: Graft-versus-host hemolysis (GVHH) syndrome develops in approximately half of patients undergoing ABO-unmatched liver transplantation. The clinical and laboratory presentations of GVHH syndrome often mimic acute rejection, leading to liver biopsy for definitive diagnosis. The purpose of this study was to investigate if there are specific histological findings that permit diagnosis of GVHH syndrome and to assess the relationship between GVHH syndrome and rejection., Methods: Clinical and laboratory evidence of GVHH syndrome, results of liver biopsy, and clinical outcome were assessed in 30 ABO-unmatched liver transplant recipients. Biopsy results were compared with those of two control groups consisting of patients who had normal liver test findings (protocol biopsy) and rejection., Results: Sixteen of the 30 patients (53%) had evidence of GVHH syndrome. Erythrophagocytosis was noted in each biopsy specimen, and the degree of phagocytosis correlated significantly with the amount of blood given after postoperative day 5 (r = 0.9; P < 0.02). Electron-microscopic studies performed randomly in 5 patients showed that the red cells were located in Kupffer cells. In contrast, erythrophagocytosis was minimal in the two control groups. Despite an incidence and severity of rejection similar to those in other liver transplant patients, serum transaminase levels were significantly higher in patients with GVHH syndrome., Conclusions: Erythrophagocytosis is a sensitive histological marker of GVHH syndrome. The severity of rejection and response to antirejection therapy should be monitored by markers other than transaminases in patients with GVHH syndrome.

Background: Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive, antinatriuretic forces such as the renin aldosterone angiotensin system and the sympathetic nervous system, and vasodilatory, natriuretic agents such as atrial natriuretic factor (ANF). Patients with diuretic resistant refractory ascites may require peritoneovenous shunting (PVS) to control ascites., Methods: To study the factors responsible for the improvement in sodium homeostasis post-PVS, we compared the response to ANF infusion before and 1 month after PVS in 6 patients with massive ascites., Results: Before PVS, sodium excretion at baseline and in response to ANF infusion was blunted but became more normal post-PVS. ANF infusion post-PVS induced a significant increase in the glomerular filtration rate and filtration fraction and also in distal delivery of sodium. ANF's distal effect of increasing the fractional excretion of distally delivered sodium was present pre-PVS and was not significantly increased post-PVS. Changes in sodium handling were accompanied by a significant decrease in antinatriuretic forces (baseline aldosterone, 2079 +/- 507 vs. 647 +/- 17 nmol/L; P < 0.04) post-PVS., Conclusions: The improvement in sodium homeostasis and response to ANF infusion post-PVS appears to be associated with the decrease in antinatriuretic forces with the loss of massive refractory ascites. Thus, PVS restores the balance toward ANF responsiveness.

Emergency surgery should be considered one of the treatment options for the patient with acute variceal bleeding in whom the usual nonsurgical modes of therapy fail, and who is deemed fit to tolerate a major operation. A total shunt (portacaval or mesocaval) is recommended for most of these patients, although a distal splenorenal shunt might be considered for some very good risk, nonalcoholic patients who have only moderate bleeding. Devascularization procedures have a limited role in the emergency situation, but they may be useful in patients who are nonshuntable because of splanchnic venous thrombosis. The Sugiura type of operation is appropriate for the nonalcoholic patient, and esophageal transection is appropriate for the alcoholic patient with cirrhosis. Patients with end-stage nonalcoholic liver disease should also be considered for liver transplantation.

The long-term renal and hemodynamic effects of the peritoneovenous shunt for intractable ascites were studied in 11 patients to elucidate the mechanism of its persistent beneficial effect. Sodium balance studies were performed in 7 patients. All had patent shunts and no clinically detectable ascites. On a 20-mEq sodium diet, the mean sodium excretion was 17.2 +/- 5.3 mEq/day which was increased over the preoperative mean of 2.4 +/- 0.4 (p < 0.025) on the same diet. There was a 100% increase in creatinine clearance over the preoperative level (p < 0.0005). The mean plasma renin activity and serum aldosterone levels were within normal limits in most patients, and the sodium excretion correlated inversely with the levels of each. During 100-mEq sodium challenge diet, the sodium excretion ranged from 4 to 130 mEq/day with a mean of 56.1 +/- 16.5 and with 6 of the 7 patients displaying sodium retention. On this diet the mean creatinine clearance was 104.3 +/- 6.4 ml/min, and the mean plasma renin activity and serum aldosterone levels had decreased physiologically with the higher sodium intake. Again the sodium excretion correlated inversely with the serum aldosterone on the 100-mEq sodium diet. In 8 patients, the portal pressure, as reflected by the wedge hepatic vein pressure, had decreased by a mean of 37% (p < 0.0005). But, despite this, 2 of the 8 patients had major variceal hemorrhages postoperatively. There was a significant inverse correlation between the increase in sodium excretion and the fall in portal pressure in 4 patients. Thus, sodium retention in cirrhosis is multifactorial with the reninaldosterone system and, possibly, portal hypertension per se both playing a role. Peritoneovenous shunting in carefully selected patients partially reverses the sodium retention and renders patients more manageable over the long term.

The effect of peritoneovenous shunting on body composition has been studied in 7 cirrhotic patients undergoing a successful shunt and 3 patients in whom the shunt was unsuccessful. In the 7 patients with functioning shunts, their weight had decreased by a mean of 9 kg (p less than 0.001) by 6 wk after initial diuresis, natriuresis, and kaliuresis, and was associated with a decrease in total body potassium (TBK) but not total body nitrogen (TBN). This resulted in a significant decrease in the TBK/TBN ratio from 2.12 +/- 0.74 to 1.66 +/- 0.20 (p less than 0.01). By a mean of 14 mo, in these 7 patients there was a significant increase in mean TBN (from 1.54 +/- 0.10 to 1.84 +/- 0.10, p less than 0.005) associated with an improvement in the mean nitrogen index (from 0.74 +/- 0.04 to 0.88 +/- 0.04, p less than 0.005). These changes were associated with a significant increase in nonalcoholic calories, a nonsignificant increase in protein consumption, and a positive nitrogen balance. After the initial kaliuresis, mean potassium balance remained constantly positive (+22.7 +/- 3.4 mmol/day), serum aldosterone levels normalized, and TBK increased. In contrast, 3 patients with failed peritoneovenous shunting continued to lose weight significantly despite the presence of ascites; TBN and nitrogen index also decreased. In conclusion, body composition studies appear to have confirmed the clinical observation that cirrhotic patients with massive ascites have depleted body protein which is gradually repleted only after successful shunting. In this situation TBK, long used as a measure of lean body mass, is less satisfactory than TBN and nitrogen index. This improvement in body protein appears to be explained by an increased dietary intake associated with improved nitrogen balance, but these changes are not found in patients in whom the shunt failed.

Fifteen patients with chronic liver disease having a peritoneovenous shunt for chronic intractable ascites were studied prospectively for renal function and hemodynamic changes during balance studies, pre-, peri-, and postoperatively. Shunt insertion caused a rapid redistribution of ascites into the intravascular compartment with hemodilution and significant rises in cardiac output (9 patients) (P less than 0.025) renal blood flow (3 patients) (P less than 0.025), and creatinine clearance (15 patients) (P less than 0.005), and decreases in plasma renin activity (10 patients) and serum aldosterone levels (9 patients) (P less than 0.025). Despite these changes, small repeated doses of furosemide were required to start and maintain a diuresis and natriuresis with sodium excretion rising from 7.2 +/- 4.1 to 174 +/- 44 meq/day (P less than 0.0005) in the 15 patients. At 2 wk postoperatively, the 15 patients had lost a mean of 7.5 kg in weight associated with a persistent improvement in creatinine clearance and a continued natriuresis, 15.9 +/- 7 mEq/day (P less than 0.005), despite no statistically significant change in cardiac output (7 patients) or renal blood flow (4 patients) compared with preoperative levels. This operation is an effective therapy for refractive ascites, but the incidence of potentially fatal complications makes us hesitate to recommend it except for patients resistant to normal conservative measures.