María-Vega Catalina

Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD era

Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End‐Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02‐1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00‐1.06; P = .05) so that each 1‐mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95% CI]; MELD score variables: 0.71 [0.62‐0.80], MELD score variables, age, and HVPG 0.76: [0.69‐0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved. (HEPATOLOGY 2005;42:793–801.)

Comparison of transcatheter arterial embolization and surgery for treatment of bleeding peptic ulcer after endoscopic treatment failure.

PURPOSE To compare the outcomes of embolotherapy and surgery as salvage therapy after therapeutic endoscopy failure in the treatment of upper gastrointestinal peptic ulcer bleeding. MATERIALS AND METHODS Retrospective analysis of 70 cases of refractory peptic upper gastrointestinal hemorrhage was performed. Thirty-one cases were managed with embolotherapy and 39 were managed surgically. Demographic variables, underlying conditions, clinical findings, endoscopic treatment, transfusion requirements before and after alternative therapeutic approach, length of hospital stay, and outcomes including recurrent bleeding, need for surgery after initial alternative treatment, and in-hospital death were recorded. RESULTS Patients who received embolotherapy were older (75.2 years +/- 10.9 vs 63.3 years +/- 14.5; P <.001) and had greater incidences of heart disease (67.7% vs 20.5%; P <.001) and previous anticoagulation treatment (25.8% vs 5.1%; P =.018). There were no differences in the rest of the pretreatment variables. No differences were found between the embolotherapy and surgery groups in the incidence of recurrent bleeding (29% vs 23.1%), need for additional surgery (16.1% vs 30.8%), or death (25.8% vs 20.5). CONCLUSIONS The lack of differences between these two treatment alternatives, despite the more advanced age and greater prevalence of heart disease in the embolotherapy group, provides support for future prospective randomized studies aimed to evaluate the role of embolotherapy in the management of refractory peptic ulcer bleeding.

Value of the hepatic venous pressure gradient to monitor drug therapy for portal hypertension: a meta-analysis.

OBJECTIVES:The use of the hepatic venous pressure gradient (HVPG) to assess the efficacy of the pharmacological treatment of portal hypertension in cirrhosis is controversial. Our aim was to establish whether target HVPG reduction predicts variceal bleeding in cirrhotic patients receiving variceal bleeding prophylaxis.METHODS:Data sources were MEDLINE, EMBASE, Cochrane Controlled Trials Register, citation lists, and abstracts (most recent search March 2006). Cohorts of patients on drug therapy from randomized and nonrandomized studies correlating variceal bleeding and HVPG change were used. Heterogeneity was explored by metaregression analysis.RESULTS:Ten studies totaling 595 patients undergoing two HVPG measurements were identified. The RR of bleeding was lower in patients achieving an overall (HVPG ≤12 mmHg or decrease ≥20%) (0.27, 95% CI 0.14–0.52), complete (HVPG ≤12 mmHg) (0.48, CI 0.28–0.81), or partial (HVPG decrease ≥20%) (0.41, CI 0.20–0.81) response, with significant heterogeneity. Regression analysis identified the interval between the HVPG measurements significantly associated with the RR of bleeding. Heterogeneity was no longer significant after exclusion of an outlier trial, which showed the longest interval to HVPG remeasurement and the lowest quality score. Even considering nonevaluable patients because of bleeding as HVPG responders, the RR of bleeding was lower in overall responders than in nonresponders (0.66, CI 0.51–0.86). Overall response was associated with lower liver-related mortality (RR 0.58, CI 0.37–0.91).CONCLUSIONS:Current evidence supports the validity of HVPG end points to monitor drug therapy efficacy for variceal bleeding prophylaxis. HVPG monitoring also provides valuable prognostic information.

Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure.

Abstract Hyperdynamic circulation and portal hypertension characterize acute on chronic liver failure (AoCLF), partially because of circulating mediators. Molecular Absorbents Recirculating System (MARS) may remove some of these substances. The objective of this study was to evaluate the effect of MARS on portal pressure, systemic haemodynamic and endogenous vasoactive systems. MARS treatment was performed in four patients with AoCLF (mean age 36.2 ± 3.1 years; Child–Pugh C 11 ± 1.8 points; three AAH and one NASH). Systemic and splanchnic haemodynamic measurements were performed before and after each session. Plasmatic renin activity (PRA) and NE were measured at baseline, at the end of the sessions and 10 days after MARS. All patients had severe portal hypertension (HVPG = 23 ± 7 mmHg) and pronounced hyperdynamic circulation (MAP 77.8 ± 11.7 mmHg; CO 11.2 ± 1.6 L/min; SVRI 478.5 ± 105 dyne s/cm5). HVPG decreased at the end of the first session in all patients (23 ± 7 mmHg vs 17.3 ± 9.9 mmHg; P = 0.05; mean decrease 32 ± 24%) because of a decrease in WHVP (40.7 ± 5.6 mmHg vs 34 ± 9.6 mmHg; P = 0.025; mean decrease 18 ± 19%). MARS significantly attenuated hyperdynamic circulation as shown by a decrease in CO (11.2 ± 1.6 L/min vs 9.4 ± 2.1 L/min; mean decrease 12.3%), with an increase in MAP (77.8 ± 11.7 mmHg vs 84.2 ± 8 mmHg; mean increase 9.2%) and in SVRI (478.5 ± 105 dyne s/cm5 vs 622 ± 198 dyne s/cm5; mean increase 41%). PRA and NE decreased significantly (14.2 ± 17.2 ng/mL/h vs 3.7 ± 3.4 ng/mL/h; 1319 ± 1002 pg/mL vs 617 ± 260 pg/mL, respectively). The NE decrease was correlated to HVPG decrease (r = 1, P = 0.01). MARS decreases portal hypertension and ameliorates hyperdynamic circulation in patients with AoCLF, probably mediated by clearance of vasoactive substances. Further studies are necessary to confirm these results.

Cardiac dysfunction during liver transplantation: incidence and preoperative predictors.

Background. The aim was to investigate the cardiac response during liver transplantation (LT) and analyze its relationship with clinical factors, echocardiographic, and hemodynamic findings. Methods. All patients undergoing LT for cirrhosis from 1998 to 2004 were included. Clinical data, comprehensive echocardiography, hepatic, and right heart hemodynamic measurements were analyzed. During LT patients underwent continuous right-heart pressure monitorization. Measurements 10 min after reperfusion were compared with baseline values. Abnormal cardiac response was defined as a decrease in left ventricular stroke work index despite a rise in pulmonary wedge capillary pressure. Predictors of abnormal cardiac response were investigated using logistic regression. Results. Data were available from 209 patients (mean age 52 (9) yrs; Child A 27; B 93; C 89) with a mean model for end-stage liver disease score 16.3 (4.7). Abnormal cardiac response was observed in 47 (22.5%) patients after reperfusion. Patients who developed this response had hyponatremia, lower central venous pressure, lower pulmonary artery pressure, and lower pulmonary wedged capillary pressure. Abnormal cardiac response was related to a longer postoperative intubation time. Conclusion. Abnormal cardiac response is observed during LT and may be a manifestation of occult cirrhotic cardiomyopathy. This finding is underestimated with usual diagnostic tools and could be related to indirect signs of circulatory dysfunction of advanced liver disease.

Risk factors for developing de novo autoimmune hepatitis associated with anti-glutathione S-transferase T1 antibodies after liver transplantation.

De novo autoimmune hepatitis (de novo AIH) is a rare form of graft dysfunction that develops after liver transplantation (LT) in patients transplanted for conditions other than autoimmune disorders. Although characterized by biochemical, serological, and histological features of AIH, de novo AIH is sometimes associated with atypical serum autoantibodies, many of which are directed against glutathione S‐transferase T1 (anti‐GSTT1). GSTT1 donor/recipient genotype mismatch has been suggested as a necessary condition for the appearance of autoantibodies and de novo AIH. However, clinically evident disease is not observed in all patients with anti‐GSTT1 antibodies. We examined the incidence of de novo AIH and its conditioning (risk) factors in patients with anti‐GSTT1 antibodies. Anti‐GSTT1 autoantibodies were detected in 29 of 419 [6.9%; 95% confidence interval (CI), 4.9–9.8] consecutive adult LT recipients with donor/recipient GSTT1 mismatch. Twenty of 27 assessable patients (74%) developed de novo AIH after a median follow‐up of 26 months (95% CI, 19.2–32.8). The probability of de novo AIH was 11%, 44%, and 60% 12, 24, and 36 months after LT, respectively. No relationship emerged between de novo AIH and recipient gender, donor and recipient age, rejection episodes, immunosuppressive regime, allelic GSTT1 expression, human leukocyte antigen distribution, or cytomegalovirus infection. Multivariate analysis identified male donor [hazard ratio (HR), 3.3; 95% CI, 1.18–9.26; P = 0.018], nonalcoholic etiology (HR, 4.67; 95% CI, 1.64–13.3; P = 0.002), and high anti‐GSTT1 titer (HR, 2.98; 95% CI, 1.04–8.57; P = 0.035) as independent predictors of de novo AIH. Most patients with anti‐GSTT1 antibodies and donor/recipient GSTT1 mismatch developed clinically evident de novo AIH after LT. The risk of developing the disease was increased by male donor gender, nonalcoholic etiology of original liver disease, and a high anti‐GSTT1 titer. Liver Transpl 15:530–539, 2009.

Randomized controlled trial of aspiration needle versus automated biopsy device for transjugular liver biopsy.

PURPOSE The efficacy and safety of transjugular liver biopsy used to obtain liver specimens in patients with coagulation disorders have been widely proven. However, histopathologic examination is not always possible because of fragmented samples provided by the aspiration technique. Recently, an automated device with a Tru-Cut-type needle was designed. In this randomized controlled trial, the use of this new device is compared with the traditional method in terms of efficacy and safety. METHOD Fifty-six patients were included in the study; 28 were randomized to undergo the aspiration technique and 28 were randomized to undergo the automated biopsy technique. RESULTS Correct positioning of the device was achieved in 93% of patients undergoing the aspiration technique and 96% of patients undergoing the automated biopsy technique (P = NS). Mean duration of the procedure and total number of passes were significantly higher in the aspiration needle group than in the automated device group (22.6 min +/- 12.6 vs 15.5 min +/- 9.4; P = .03, and 3.3 min +/- 1.9 vs 1.5 min +/- 0.63; P < .001, respectively). The number of portal tracts was significantly higher in the automated device group (4.7 +/- 2.5 vs. 2.7 +/- 3.4; P < .05). Adequate specimens for histopathologic evaluation were obtained in 26 patients in the automated device group and 24 patients in the aspiration needle group (92.8% vs 85.7%; P = NS), but a definite histopathologic diagnosis was more frequently obtained with the automated biopsy device (68% vs 43%; P = .05). No significant differences were observed in complication rates (7.14% vs. 10.7%; P = NS). CONCLUSION The automated biopsy device for transjugular liver biopsy is more effective than an aspiration needle in obtaining good samples for a definite histologic diagnosis.

Prognostic value of hepatic venous pressure gradient in patients with compensated chronic hepatitis C-related cirrhosis

Abstract Background and aim. Hepatic venous pressure gradient (HVPG) is the main predictor of clinical decompensation in cirrhotic patients with compensated disease of any etiology without varices. However, the predictive factors of decompensation are not so well known in patients with hepatitis C-related compensated cirrhosis, in whom etiology-based therapy is difficult. The aim of this study was to identify predictors of decompensation in patients with compensated chronic hepatitis C (CHC)-related cirrhosis with and without esophageal varices (Baveno stages 1 and 2). Methods. The study population was a cohort of 145 of such consecutive patients who received hepatic hemodynamic study. All patients were similarly followed every 6 months. Through multivariate Cox regression and bootstrap analyses, a prognostic index (PI) was developed and tested in an external cohort (n = 38). Results. Forty-two patients (29%) suffered a first decompensation episode after a median follow-up of 27 months (2–110). Cox regression analysis identified HVPG (hazard ratio (HR) 1.11; 95% confidence interval (CI): 1.05–1.17) and albumin (HR 0.42; 95% CI: 0.22–0.82) as independent predictors of decompensation. Bootstrapping confirmed that HVPG (95% CI: 1.05–1.18) and albumin (95% CI: 0.12–0.74) were the most robust predictive variables. Using a cut-off level of 2.5, the PI [4 + (0.11 × HVPG - 0.8 × albumin)] was able to distinguish two populations of patients with very different risks of decompensation in both the exploratory and validation cohorts. A time-dependent ROC curve identified HVPG as the best predictive variable. Conclusion. HVPG and albumin are independent predictors of clinical decompensation in patients with compensated CHC-related cirrhosis irrespective of the existence of varices.

The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis

Background: In cirrhosis, repeated flares of portal pressure and collateral blood flow provoked by postprandial hyperaemia may contribute to variceal dilation and rupture. Aim: To examine the effect of the extent of the collateral circulation on the postprandial increase in portal pressure observed in cirrhosis. Patients and methods: The hepatic venous pressure gradient (HVPG), hepatic blood flow and azygos blood flow were measured in 64 patients with cirrhosis before and after a standard liquid meal. Results: Peak increases in HVPG (median+14.9%), hepatic blood flow (median+25.4%), and azygos blood flow (median+32.2%) occurred at 30 min after the meal. Compared with patients with marked postprandial increase in HVPG (above the median, n = 32), those showing mild (<15%, n = 32) increase in HVPG had a higher baseline azygos flow (p<0.01) and underwent a greater postprandial increase in azygos flow (p<0.02). Hepatic blood flow increased similarly in both groups. Postprandial increases in HVPG were inversely correlated (p<0.001) with both baseline azygos flow (r = −0.69) and its postprandial increase (r = −0.72). Food intake increased nitric oxide products in the azygos (p<0.01), but not in the hepatic vein. Large varices (p<0.01) and previous variceal bleeding (p<0.001) were more frequent in patients with mild increase in HVPG. Conclusions: Postprandial hyperaemia simultaneously increases HVPG and collateral flow. The extent of the collateral circulation determines the HVPG response to food intake. Patients with extensive collateralisation show less pronounced postprandial increases in HVPG, but associated with marked flares in collateral flow. Collateral vessels preserve their ability to dilate in response to increased blood flow.

Toxicidad hepática por ingesta de setas: curso clínico y nuevas perspectivas de tratamiento

Resumen El envenenamiento por setas, fundamentalmente del genero Amanita , es una causa infrecuente de insuficiencia hepatica en nuestro medio pero constituye una urgencia medica por su elevada morbilidad y mortalidad. Los sintomas tipicos iniciales de nauseas, vomitos, dolor abdominal y diarrea son inespecificos y pueden ser confundidos con una gastroenteritis. Si no se trata adecuada y precozmente, en pocos dias se puede desarrollar un fallo renal y hepatico, lo que hace necesario en ocasiones la realizacion de un trasplante hepatico. Se exponen 3 casos de intoxicacion por setas que presentaron distinto curso clinico, desde la recuperacion completa con el tratamiento medico convencional, hasta el desarrollo de insuficiencia hepatica aguda grave. Uno de los pacientes fue trasplantado y otro tratado con dialisis de albumina ( molecular absorbent recycling system [MARS]), este ultimo caso con muy buena evolucion. Aunque no hay estudios clinicos controlados respecto al tratamiento de esta afeccion, se han establecido unas pautas basadas en las experiencias de distintos autores. La penicilina G y la silimarina parecen ser de utilidad. El desarrollo de nuevas tecnicas de depuracion extracorporea, fundamentalmente el MARS, puede suponer un importante sistema de soporte en el tratamiento de estos pacientes.