Dominique Valla

Assessment of the benefits and risks of percutaneous biopsy before surgical resection of hepatocellular carcinoma

BACKGROUND/AIMSnBecause of a potential risk of needle tract seeding, the use of ultrasound (US)-guided biopsy for the diagnosis of hepatocellular carcinoma (HCC) is controversial. This study was aimed at determining the usefulness, accuracy and safety of this technique as well as the incidence of needle tract seeding.nnnMETHODSnFrom 1986 to 1996, 137 patients who underwent resection or transplantation for suspected HCC had US-guided biopsy before surgery. The analysis of the resected liver was compared to the results of biopsy. Patients were assessed with a mean follow up of 38 months.nnnRESULTSnThe diagnosis of HCC was established by biopsy in 122 patients (89%). Thirteen of the 15 patients with negative biopsy were shown to have HCC after surgery. The remaining two patients had non-malignant nodules. Sensitivity and accuracy of US-guided biopsy were 90 and 91%, respectively. Accuracy was significantly influenced by the location of the nodule but not by its size. Needle tract seeding occurred in two patients (1.6%).nnnCONCLUSIONSnIn this series, the incidence of needle tract seeding was less than 2% and no recurrence was observed after local excision. This risk should be balanced with the risk of deciding an aggressive treatment in a patient without malignancy. Patients with negative biopsy should undergo a second biopsy and/or repeated investigations by imaging techniques.

A Single-Center Surgical Experience of 122 Patients With Single and Multiple Hepatocellular Adenomas

BACKGROUND & AIMSnHepatocellular adenoma (HA) is associated with risk of bleeding and malignancy, justifying resection. Patients with multiple forms of HA are difficult to manage. We evaluated the characteristics and outcome of 122 patients with single and multiple HAs after surgery.nnnMETHODSnFrom 1990 to 2004, 122 patients (14 male) underwent surgical resection. Complications (hemorrhage and malignancy) were assessed according to size, number, and histologic subtype (steatotic, telangiectatic, and unclassified), with a mean follow-up period of 70 months.nnnRESULTSnHemorrhagic HA occurred in 21% of cases and malignant HA occurred in 8%. Risk of complications was not related to the number of HAs but was associated with size (>5 cm), especially of telangiectatic and unclassified subtypes. Patients with steatotic HA had a low risk of complications. Malignant HA was more frequent in men (43%); all patients treated by partial resection survived, without recurrent malignancy, after a mean follow-up period of 78 months. After 109 patients with benign HA revealed recurrence or progression of HA in 8% and regression in 9% of cases. No complications were observed in 11 women who became pregnant during the follow-up period.nnnCONCLUSIONSnPatients with HAs greater than 5 cm, telangiectatic or unclassified subtypes, and men have an increased risk of complicated disease; resection should be restricted to these patients. The risk of complications was not related to the number of HAs, so patients with multiple HAs do not need liver transplantation.

Aiming at minimal invasiveness as a therapeutic strategy for Budd‐Chiari syndrome

The 1‐year spontaneous mortality rate in patients with Budd‐Chiari syndrome (BCS) approaches 70%. No prospective assessment of indications and impact on survival of current therapeutic procedures has been performed. We evaluated a therapeutic strategy uniformly applied during the last 8 years in a single referral center. Fifty‐one consecutive patients first received anticoagulation and were treated for associated diseases. Symptomatic patients were considered for hepatic vein recanalization; then for transjugular intrahepatic portosystemic shunt (TIPS), and finally for liver transplantation. The absence of a complete response led to the next procedure. Assessment was according to the strategy, whether procedures were technically applicable and successful. At entry, median (range) Child‐Pugh score and Clichy prognostic index were 8 (5–12), and 5.4 (3.1–7.7), respectively. A complete response was achieved on medical therapy alone in 9 patients; after recanalization in 6, TIPS in 20, liver transplantation in 9, and retransplantation in 1. Of the 41 patients considered for recanalization, the procedure was not feasible in 27 and technically unsuccessful in 3. Of the 34 patients considered for TIPS, the procedure was considered not feasible in 9 and technically unsuccessful in 4. At 1 year of follow‐up, a complete response to TIPS was achieved in 84%. One‐ and 5‐year survival from starting anticoagulation were 96% (95% CI, 90–100) and 89% (95% CI, 79–100), respectively. In conclusion, excellent survival can be achieved in BCS patients when therapeutic procedures are introduced by order of increasing invasiveness, based on the response to previous therapy rather than on the severity of the patients condition. (HEPATOLOGY 2006;44:1308–1316.)

Evidence for a role of nonalcoholic steatohepatitis in hepatitis C: A prospective study

Although steatosis is a common histological feature in chronic hepatitis C (CHC), nonalcoholic steatohepatitis (NASH) has not yet been clearly characterized in this context. The aim of this prospective study was to investigate the characteristics of patients with NASH and CHC. Biopsies were categorized as CHC alone (178 patients [57%]), CHC+steatosis (94 patients [34%]), or CHC+NASH (24 patients [9%]). Patients with CHC+NASH had significantly higher AST and triglyceride levels and lower high‐density lipoprotein (HDL) cholesterol or total cholesterol than patients with CHC+steatosis. They also showed more steatosis and higher METAVIR fibrosis stage than patients with CHC+steatosis. Genotype 3 was more frequent in patients with CHC+NASH than in patients with CHC+steatosis or CHC alone. Patients with genotype 3 and CHC+NASH were similar to those with CHC+steatosis or with CHC alone according to triglyceride or the homeostasis model for assessment of insulin resistance (HOMA‐IR), whereas in patients with genotype 1, HOMA‐IR and triglyceride increased progressively from CHC alone to CHC+steatosis to CHC+NASH. In multivariate analysis, triglyceride and HDL cholesterol were predictors of NASH in patients with genotype 1, whereas in patients with genotype 3, AST was the only predictor. Conclusion: Patients with CHC+NASH differ significantly from those with CHC+steatosis and CHC alone in terms of biological and metabolic parameters and more advanced histopathological lesions. NASH is more common in genotype 3 and is not associated with metabolic dysfunctions in this subgroup, suggesting that NASH may complicate steatosis in CHC irrespective of etiology of steatosis. (HEPATOLOGY 2007.)

Portal vein thrombosis, cirrhosis, and liver transplantation

Portal vein thrombosis is not uncommon in candidates for transplantation. Partial thrombosis is more common than complete thrombosis. Despite careful screening at evaluation, a number of patients are still found with previously unrecognized thrombosis per-operatively. The objective is to recanalize the portal vein or, if recanalization is not achievable, to prevent the extension of the thrombus so that a splanchnic vein can be used as the inflow vessel to restore physiological blood flow to the allograft. Anticoagulation during waiting time and transjugular intrahepatic portosystemic shunt (TIPS) are two options to achieve these goals. TIPS may achieve recanalization in patients with complete portal vein thrombosis. However, a marked impairment in liver function, which is a characteristic feature of most candidates for transplantation, may be a contraindication for TIPS. Importantly, the MELD score is artificially increased by the administration of vitamin K antagonists due to prolonged INR. When patency of the portal vein and/or superior mesenteric vein is not achieved, only non-anatomical techniques (renoportal anastomosis or cavoportal hemitransposition) can be performed. These techniques, which do not fully reverse portal hypertension, are associated with higher morbidity and mortality risks. Multivisceral transplantation including the liver and small bowel needs to be evaluated. In the absence of prothrombotic states that may persist after transplantation, there is no evidence that pre-transplant portal vein thrombosis justifies long term anticoagulation post-transplantation, provided portal flow has been restored through conventional end-to-end portal anastomosis.

Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy.

BACKGROUND & AIMSnAcute liver insufficiency is a rare complication of anorexia nervosa. The mechanisms for this complication are unclear. The aim of this study was to describe patient characteristics and clarify the mechanisms involved.nnnMETHODSnLiver specimens from 12 patients (median age, 24 years; median body mass index, 11.3 kg/m(2)), with a prothrombin index <50% and/or an International Normalized Ratio >1.7 and anorexia nervosa as the only cause for acute liver injury were analyzed. A detailed pathologic examination was performed, including under electron microscopy.nnnRESULTSnLiver cell glycogen depletion was a constant finding. There was a contrast between the increase in serum alanine aminotransferase (56 times normal on average; 1,904 IU/L) and the absence of significant hepatocyte necrosis on histology. Centrilobular changes (trabecular atrophy and/or sinusoidal fibrosis) were observed in 6 patients. There were rare or no (<5%) terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes, suggesting that apoptosis was not the primary mechanism. Hepatocytes from 4 patients showed numerous autophagosomes, a morphologic hallmark of autophagy, on electron microscopy. In contrast, the mitochondria, endoplasmic reticulum, and nuclei were normal in most cells. These features were absent in 11 control patients. The outcome was favorable in all patients, with a rapid return to normal liver function.nnnCONCLUSIONSnAnorexia nervosa with extremely poor nutritional status should be added to the list of conditions causing acute liver insufficiency. Our findings show that starvation-induced autophagy in the human liver may be involved in liver cell death during anorexia nervosa, even though other mechanisms of liver cell damage could also play a role.

Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study

Background: Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. Aims: To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. Methods: Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4–6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. Results: Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. Conclusions: This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.

Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy

Background and aims: The rates of fibrosis progression in chronic hepatitis C are significantly different between males and females. The antifibrogenic effect of oestrogen has been proposed, possibly via inhibition of stellate cells. The aim of this study was to evaluate the severity of chronic hepatitis C in women, in relation to the menopause, steatosis and hormone replacement therapy (HRT). Methods: From November 2003 to October 2004, women with chronic hepatitis C were enrolled prospectively. A questionnaire was completed prospectively and a blood sample was obtained on the day of biopsy. We identified characteristics associated with moderate/severe fibrosis using univariate and multivariate analysis. Results: 251 women were included in the study. 122 women (52%) were menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe fibrosis (F2–F4, Metavir score) had a longer known duration of infection (>15 years), a higher body mass index and presented with steatosis more frequently than 190 (76%) women with mild fibrosis (F0–F1). Women with F2–F4 were more often menopausal (67% v 47%). The probability of fibrosis F2–F4 was lower for menopausal women receiving HRT (pu200a=u200a0.012). Steatosis was more frequent and more severe in menopausal women. Conclusions: Severity of fibrosis was associated with a longer duration of infection (>15 years), a higher body mass index, advanced steatosis and the menopause. Menopausal women receiving HRT presented with a lower stage fibrosis. These results reinforce the hypothesis of a protective role of oestrogens in the progression of fibrosis. Steatosis may be implicated in the progression of fibrosis after the menopause.

Pregnancy in women with known and treated Budd–Chiari syndrome: Maternal and fetal outcomes

BACKGROUND/AIMSnBudd-Chiari syndrome (BCS) mainly affects women of childbearing age. We aimed to clarify whether pregnancy, a thrombotic risk factor, should be contraindicated in patients with known and treated BCS.nnnMETHODSnA retrospective study of pregnancy in women with known and treated BCS.nnnRESULTSnSixteen women had 24 pregnancies. Nine women had undergone surgical or radiological treatment. Anticoagulation was administered during 17 pregnancies. Seven fetuses were lost before gestation week 20. Deliveries occurred between week 20 and 31 in two patients, week 32 and 36 in eleven and after week 37 in four. There was one stillbirth, but 16 infants did well. Factor II gene mutation was a factor for a poor outcome of pregnancies. In two patients, symptomatic thrombosis recurred during pregnancy or postpartum. All patients were alive after a median follow-up of 34 months after the last delivery. Bleeding at delivery, although non-lethal, occurred only on anticoagulation therapy.nnnCONCLUSIONSnWhen known and treated BCS is well controlled, pregnancy should not be contraindicated as maternal outcome, and fetal outcome beyond gestation week 20, are good. The risk-benefit ratio of anticoagulant therapy needs to be further clarified. Patients should be fully informed of the persistent risks of such pregnancies.

Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome

In Budd-Chiari syndrome (BCS), thrombosis develops in the hepatic veins or inferior vena cava. To study the relationship between hypofibrinolysis and BCS, we measured plasma levels of fibrinolysis proteins in 101 BCS patients and 101 healthy controls and performed a plasma-based clot lysis assay. In BCS patients, plasminogen activator inhibitor 1 (PAI-1) levels were significantly higher than in controls (median, 6.3 vs 1.4 IU/mL, P < .001). Thrombin-activatable fibrinolysis inhibitor and plasmin inhibitor levels were lower than in controls (13.8 vs 16.9 microg/mL and 0.91 vs 1.02 U/L, both P < .001). Median plasma clot lysis time (CLT) was 73.9 minutes in cases and 73.0 minutes in controls (P = .329). A subgroup of cases displayed clearly elevated CLTs. A CLT above the 90th or 95th percentile of controls was associated with an increased risk of BCS, with odds ratios of 2.4 (95% confidence interval, 1.1-5.5) and 3.4 (95% confidence interval, 1.2-9.7), respectively. In controls, only PAI-1 activity was significantly associated with CLT. Analysis of single nucleotide polymorphisms of fibrinolysis proteins revealed no significant differences between cases and controls. This case-control study provides the first evidence that an impaired fibrinolytic potential, at least partially caused by elevated PAI-1 levels, is related to the presence of BCS.