Transjugular intravascular ultrasound for the evaluation of hepatic vasculature and parenchyma in patients with chronic liver disease.

BACKGROUND: The evaluation of the hepatic parenchyma in patients with chronic liver disease is important to assess the extension, localization and relationship with adjacent anatomical structures of possible lesions. This is usually performed with conventional abdominal ultrasound, CT-scan or magnetic resonance imaging. In this context, the feasibility and the safety of intravascular ultrasound in the liver have not been assessed yet. METHODS: We tested the safety and performance of an intracardiac echography (ICE) catheter applied by a transjugular approach into the hepatic veins in patients with chronic liver disease undergoing hepatic hemodynamic measurements. RESULTS: Five patients were enrolled in this pilot study. The insertion of the ICE catheter was possible into the right and middle, but not into the left hepatic vein. The position of the ICE was followed using fluoroscopy and external conventional ultrasound. Accurate imaging of focal hepatic parenchymal lesions, Doppler ultrasound of surrounding blood vessels and assessment of liver surface and ascites were achieved without complications. CONCLUSIONS: This study demonstrated that a diagnostic approach using an ICE device inserted in the hepatic veins is feasible, safe and well tolerated. However, it remains for the moment only an experimental investigative tool. Whether ICE adds further information regarding parenchymal lesions and associated vascular alterations as compared to other techniques, needs additional investigation.

Demographics and outcomes of severe herpes simplex virus hepatitis: a registry-based study.

BACKGROUND & AIMS: Herpes simplex virus hepatitis is a rare, but severe disease, thus far only documented by case reports and short series. The present study was based on the SRTR registry, and included all listed patients for liver transplantation from 1985 to 2009 with a diagnosis of HSV hepatitis. METHODS: We assessed demographics and outcome of all listed patients, and further conducted a case-control study, matching each transplanted patient with 10 controls. Matching criteria included: transplant status, MELD score ±5, transplant date ±6 months, and age at transplant ±5 years. During the study period, 30 patients were listed for HSV hepatitis. Of the 30 listed patients, seven recovered spontaneously and five died, prior to transplantation. The remaining 10 children and eight adults were transplanted. RESULTS: The chance of recovery was significantly higher in children than in adults (7/19 vs. 0/11, p=0.02). In children, survival was similar between HSV patients and the matched controls (5-year survival: 69% vs. 64%, p=0.89). Conversely, survival was poor in adult HSV (5-year survival: 38% vs. 65%, p=0.006), with 62% of them dying within the first 12 months. All three reported post-transplant deaths in children were independent from HSV. Among the seven adult post-transplant deaths, four were related to infection (bacterial, fungal, or viral). CONCLUSIONS: Children listed for HSV hepatitis have a significantly better survival than adults both prior and after liver transplantation. While HSV fulminant hepatitis is an appropriate indication for liver transplantation in children, it should only be performed in selected adult patients in otherwise good condition.

A simple score for predicting alcohol relapse after liver transplantation: results from 387 patients over 15 years.

BACKGROUND: Alcohol relapse can negatively influence the outcome after liver transplantation (LT). The aim of our study was to identify factors that could be associated with the recurrence of harmful alcohol consumption after LT. METHODS: A total of 387 consecutive patients (23.8% women) who underwent LT for alcoholic cirrhosis in Geneva, Switzerland, and Lyon, France, between 1989 and 2005 were evaluated. Mean +/- SD age was 51.3 +/- 7.5 years. Follow-up time was 61.2 +/- 47.5 months. Alcohol consumption relapse and potential factors associated with it were studied. RESULTS: The relapse rate of harmful alcohol consumption after LT was 11.9%. In univariate analysis, alcohol relapse was significantly associated with age greater than 50 years (P = .04), year of LT 1995 or earlier (P<.05), duration of abstinence less than 6 months (P = .02), presence of psychiatric comorbidities (P<.001), presence of a life partner (P<.05), and a high score on the High-Risk Alcoholism Relapse (HRAR) scale (P<.001). Multivariate logistic regression disclosed the following independent factors of relapse: duration of abstinence of less than 6 months (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.2-9.3) (P = .02); presence of psychiatric comorbidities (OR, 7.8; 95% CI, 3.1-20.0) (P<.001); and HRAR score higher than 3 (OR, 10.7; 95% CI, 3.8-30.0) (P = .001). In patients with none of these factors, alcohol relapse was 5%, while the presence of 1, 2, or 3 factors was associated with relapse rates of 18%, 64%, and 100% of the patients, respectively. CONCLUSIONS: In a large cohort of patients undergoing LT for alcoholic cirrhosis, a duration of abstinence of less than 6 months before wait-listing for LT, the presence of psychiatric comorbidities, or an HRAR score higher than 3 was associated with relapse into harmful drinking. The presence of more than 1 factor dramatically increased this risk over 50%. In the pre-LT evaluation in this setting, these factors should be accurately determined.

Perendoscopic variceal pressure measurement: a reliable estimation of portal pressure in patients with cirrhosis?

OBJECTIVES: In patients with cirrhosis, the hepatic venous pressure gradient (HVPG) is the reference method for the assessment of portal hypertension (PHT). Variceal pressure (VP) may be measured at endoscopy, but its relationship to the HVPG remains controversial. The aim of the study was to retrospectively compare HVPG and VP values obtained in a cohort of patients with cirrhosis and PHT. METHODS: Within 8 days (range: 6-10 days), 64 patients in a stable condition with biopsy-proven cirrhosis [alcoholic: 47; other 17; mean age: 56.5 yrs (35-70); mean Child-Pugh's score: 9.4 +/- 1.9; ascites: 37/64; previous variceal bleeding (="bleeders"): 24/64) and oesophageal varices (grade 2: 49; grade 3: 15)] underwent both measurement of the HVPG during transjugular liver biopsy and VP at endoscopy using a "home made" pressure sensitive gauge in the absence of needle puncture of the varix. Alcoholic hepatitis was present in 28 patients with alcoholic cirrhosis. RESULTS: The pressure sensitive gauge was well tolerated. The mean HVPG and VP values were 18.5 +/- 3.4 mmHg and 19 +/- 3.7 mmHg, respectively. A significant difference was observed between "bleeders" (n=24) and non "bleeders" (n=40) in terms of VP values (21.4 +/- 3.3 vs 17.2 +/- 3.2 mmHg, P<0.001), but not for HVPG values (19.4 +/- 4.1 vs 17.9 +/- 2.8 mmHg, P=0.075). A positive correlation was observed between VP and HVPG values (r=0.62, P<0.0001). CONCLUSIONS: In this group of patients with cirrhosis and oesophageal varices, a "home-made" pressure sensitive gauge allowed a non invasive perendoscopic measurement of VP. The positive correlation between VP and HVPG values suggests that measurement of VP may be a reliable estimate of portal pressure in these patients.

Surgical management and long-term outcome of complicated liver hydatid cysts caused by Echinococcus granulosus.

BACKGROUND: The aim of this retrospective study was to evaluate clinical presentation and long-term outcome of patients treated surgically for complicated liver hydatid cysts. PATIENTS AND METHODS: Eighty-four patients with liver hydatid cysts underwent an operation at the Geneva University Hospital between 1980 and 1999. Clinical presentation, postoperative morbidity, mortality, and long-term recurrence rate were evaluated. RESULTS: Among the 84 patients with liver hydatid disease, 35 patients (41%) presented complicated cysts (ie, cysts that had developed a fistula into adjacent structures or organs). In most patients, the fistula communicated with the biliary tree (n = 25), but we also observed communication with the right lung (n = 3), the right diaphragm (n = 2), liver parenchyma (n = 1), and peritoneal cavity (n = 1). Complete removal of the cystic disease was possible in 24 of 35 patients (70%). In 11 patients, fragments of cysts were not removed because of their location adjacent to main vessels. Postoperatively, 8 patients (23%) developed a severe complication (grade II and III). There were no postoperative deaths, and no recurrences of hydatid disease were observed with a median follow-up of 8.6 years (complete follow-up was obtained in 69% of patients). CONCLUSIONS: Complicated liver hydatid disease is frequent and was observed in almost half of patients operated for liver hydatid cysts at our center. Using a surgical strategy aimed at complete removal of cystic and pericystic tissue with simultaneous treatment of the fistulous tract, we observed 23% postoperative morbidity, no mortality, and no recurrence of disease with a median follow-up of >8 years.

Lymphatic vessel density and vascular endothelial growth factor-C expression correlate with malignant behavior in human pancreatic endocrine tumors.

Metastatic dissemination of tumor cells to regional lymph nodes is a common early feature of many human cancers including pancreatic adenocarcinoma. In contrast, lymph node metastasis is more variably observed in pancreatic endocrine tumors. The objective of this study was to assess the lymphatic system of human pancreatic endocrine tumors and correlate this to clinical behavior. Immunohistochemistry was performed using antibodies to two recently identified markers of lymphatic endothelium, namely, LYVE-1 and podoplanin, and to the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. As has been reported previously, we observed that in the normal pancreas, islets of Langerhans are devoid of intra-islet lymphatics, but that lymphatics are present in connective tissue in association with ducts and blood vessels. We found that both benign and malignant pancreatic endocrine tumors contain intratumoral lymphatic vessels. Lymphatic vessel density was related to the size of the tumor in benign tumors and to the presence of liver metastasis but not to lymph node metastasis in malignant tumors. VEGF-C was expressed in tumor cells: 4 of 19 (21%) benign tumors were positive, whereas 6 of 9 (67%) borderline tumors and 9 of 11 (82%) carcinomas were positive. These findings strongly suggest that lymphangiogenesis occurs in pancreatic endocrine tumors and that lymphatic invasion and the development of metastases are associated with VEGF-C expression.

Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis.

BACKGROUND/AIMS: In alcoholic hepatitis (AH), soluble TNF alpha receptor-1 (sTNF-R1) is increased. Elevated TNF alpha predicts mortality, but infection influences TNF alpha values. In patients with AH, we determined the prognostic value of TNF alpha, sTNF-R1, and lipopolysaccharide binding protein (LBP) and CD14, both involved in endotoxemia-associated inflammation. METHODS: One hundred and eight cirrhotic patients (Pugh score 10 [6-13]) and biopsy-proven AH (Maddrey's DF <32: n=46; > or =32: n=62) without associated infection were included within 8 days of admission and followed-up for 3 months. Cytokines were measured using specific immunoassays. Patients with severe AH received steroids. RESULTS: Twenty four patients died at a median time of 35 days (range: 3-89). The overall survival was 78%. Multivariate Cox regression analysis showed that sTNF-R1 was an independent predictor of mortality, (OR 4.33: 95% CI [1.12-16.75]). Pugh's score (P=0.618), Maddrey's DF (P=0.182), creatinine (P=0.197), TNF alpha (P=0.319), LBP (P=0.362), and CD14 (P=0.347) were not related to survival. CONCLUSIONS: In patients with AH, sTNF-R1 measured at admission is an independent predictor of survival at 3 months. Provided that TNF-R1 mediates the cytotoxic actions of TNFalpha, these results support the concept of dysregulated TNF alpha metabolism in AH.

Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study.

BACKGROUND/AIMS: The aim of this study is to evaluate the tolerance and effects of infliximab combined with steroids in severe alcoholic hepatitis (AH). METHODS: Twenty patients with biopsy-proven severe AH (Maddrey's score>32) received prednisone 40 mg/day for 28 days and either infliximab 5mg/kg IV (group A) or placebo (group B) at day 0. Histology, plasma interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured at baseline and at day 10. RESULTS: Infliximab was well tolerated. Histology showed no significant changes. At day 28, Maddrey's score significantly improved in group A (39 (32-53) to 12 (7-52), P<0.05 vs. baseline) but not in group B (44 (33-50) to 22 (2-59), P=NS). At day 10, IL-6 and IL-8 decreased in group A (25 pg/ml (10-85 pg/ml) to 4.5 pg/ml (2-25 pg/ml); 301 pg/ml (107-1207 pg/ml) to 14 6 pg/ml (25-252 pg/ml), P<0.01, P<0.05 vs. baseline, respectively). In group B, changes were not significant (38 pg/ml (13-116 pg/ml) to 16 pg/ml (4-128); 315 pg/ml (26-1698 pg/ml) to 110 pg/ml (27-492 pg/ml)). CONCLUSIONS: In severe AH, infliximab was well tolerated and associated with significant improvement in Maddrey's score at day 28. Although the size of this study does not allow comparison between groups, these promising results should encourage larger trials assessing the effects of this therapy on survival.

Acute effects of nitric oxide synthase inhibition on systemic, hepatic, and renal hemodynamics in patients with cirrhosis and ascites.

BACKGROUND: Nitric oxide synthase (NOS) inhibition has been demonstrated to correct systemic vasodilation and renal hypoperfusion in studies of patients with cirrhosis. In patients with decompensated cirrhosis, NOS blockade increases arterial pressure, but the acute effects on hepatic and renal hemodynamics are not known. METHODS: We examined the acute systemic, hepatic, and renal hemodynamic effects of N(G)-monomethyl-L-arginine (L-NMMA) in 10 patients with decompensated cirrhosis. After baseline measurements, 3 mg/kg L-NMMA was administered as an IV bolus. At 20 minutes, if mean arterial pressure did not increase by at least 10 mm Hg above the baseline value, a second injection of 6 mg/kg was administered. RESULTS: In 5 of 10 patients, the second injection of L-NMMA 6mg/kg was necessary to achieve at least a 10 mm Hg increase in mean arterial pressure. Acute NOS inhibition increased systemic vascular resistance and decreased cardiac output, without causing changes in the hepatic venous pressure gradient. Hepatic blood flow decreased, but the indocyanine green intrinsic clearance and extraction remained unchanged. Plasma renin activity (from 9.5 +/- 2.9 to 6.7 +/- 1.6 ng/ml/h) and urinary prostaglandin E2 (from 299 +/- 40 to 112 +/- 36 pg/ml) significantly decreased. No significant changes in glomerular filtration rate, renal plasma flow, and natriuresis occurred, however. CONCLUSIONS: Acute L-NMMA infusion in patients with decompensated cirrhosis reduced hepatic blood flow and decreased plasma renin activity and urinary prostaglandin E2, without causing significant changes in renal hemodynamics.

Persistence of mild parkinsonism 4 months after liver transplantation in patients with preoperative minimal hepatic encephalopathy: a study on neuroradiological and blood manganese changes.

Pallidal hyperintensity at magnetic resonance imaging (MRI) correlates to blood manganese (Mn) levels and parkinsonian signs in patients with cirrhosis. Similarly, metabolite changes in the basal ganglia (BG) at proton spectroscopy are related to these neurological signs. The evolution of these abnormalities after liver transplantation (OLT) is incompletely described. We evaluated 14 unselected consecutive patients with cirrhosis (minimal hepatic encephalopathy [HE] n=8, no HE n=6) before and 4 months after successful OLT for the evolution of parkinsonism using a validated scale (the United Parkinson's Disease Rating Scale, or UPDRS). Pallidal intensity at MRI, spectroscopic changes in the BG at magnetic resonance spectroscopy (MRS), and whole blood manganese concentrations were measured. After OLT in patients with preoperative minimal HE, the UPDRS scores improved, but mild parkinsonism persisted (16.1+/-3.6 to 6.2+/-4.8, P<0.05). Pallidal hyperintensity remained abnormal in 5/8 of cases, but spectroscopic changes normalized in all patients. Blood Mn remained elevated in 4/6 patients. In patients without HE, UPDRS values remained negligible (2.42+/-1.5 to 2.5+/-1.4). Pallidal hyperintensity normalized in 7/8 patients and spectroscopic changes normalized in all patients. Blood Mn remained elevated in 5/6 patients. Four months after successful OLT, patients with preoperative minimal HE and severe pallidal hyperintensity showed persistent mild parkinsonism. The role of blood manganese determination appears limited in the monitoring of MRI and parkinsonian signs changes after OLT.

Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.

BACKGROUND & AIMS: Type 1 hepatorenal syndrome (HRS) is a severe complication of cirrhosis associated with a short median survival time (<2 weeks). Although the administration of terlipressin improves renal function, its effect on survival is unknown. This study investigated predictive factors of survival in patients with type 1 HRS treated with terlipressin. METHODS: Ninety-nine patients with type 1 HRS treated with terlipressin in 24 centers were retrospectively studied. Terlipressin-induced improved renal function was defined as a decrease in serum creatinine value to <130 micromol/L or a decrease of at least 20% at the end of treatment. RESULTS: At inclusion, the Child-Pugh score was 11.8 +/- 1.6 (mean +/- SD). Terlipressin (3.2 +/- 1.3 mg/day) was administered for 11 +/- 12 days. Renal function improved in 58% of patients (serum creatinine decreased by 46% +/- 17% from 272 +/- 114 micromol/L). Median survival time was 21 days. Survival rate was 40% at 1 month. Multivariate analysis showed that improved renal function and Child-Pugh score < or =11 at inclusion were independent predictive factors of survival (P < 0.0001 and 0.02, respectively). Thirteen patients underwent liver transplantation (92 +/- 95 days after HRS onset), 10 of whom had received terlipressin and had had improved renal function. CONCLUSIONS: This retrospective uncontrolled study shows that in patients with type 1 HRS, terlipressin-induced improved renal function is associated with an increase in survival. Thus, a randomized trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed.