Emilio Fábrega

Alcohol recidivism impairs long-term patient survival after orthotopic liver transplantation for alcoholic liver disease.

The aim of this study was to evaluate the rate of alcohol recidivism after orthotopic liver transplantation (OLT) for alcoholic liver disease (ALD) and its influence on the allograft and patient survival, as well as the development of comorbidities and de novo cancers. The study was performed on 54 subjects previously analyzed and transplanted in our center for ALD, whose follow‐up was prolonged to a mean of 99.2 (SD 31.7) months (range, 14–155). Medical records were reviewed, and data on alcohol consumption, therapeutic compliance, graft evolution, rejection, infections, comorbidities, rates of de novo malignancies and other clinical events, and survival were collected. Comparisons between groups were performed by the Fishers exact test, and survival was assessed by the Kaplan‐Meier method. Survival curves were compared using the Mantel‐Cox statistic. The risk of death resulting from alcohol recidivism was analyzed with a Cox proportional hazards model. Fourteen patients who underwent transplantation for ALD (25.9%) returned to alcohol use between 5.0 and 86.9 months after OLT (median, 47.5). There was no significant association between the presence or absence of alcohol recidivism and the occurrence of graft rejection, infections, associated comorbidities after OLT, or compliance. The 5‐ and 10‐year survival rates for patients with alcohol recidivism were 92.9% and 45.1%, respectively, compared with 92.4% and 85.5%, respectively, for patients without alcohol recidivism. These figures show significantly lower survival rates in recidivistic patients after 10 years (P < 0.01, Mantel‐Cox). The fact that patients who resumed alcohol consumption have a worse 10‐year survival rate might be attributed to a higher frequency of deaths, primarily from cancer and cardiovascular events. (Liver Transpl 2005;11:420–426.)

Outcome of autoimmune hepatitis after liver transplantation.

BACKGROUND Recurrence of autoimmune hepatitis after liver transplantation is not rare, but there is little information about its time of onset, risk factors, response to treatment and prognosis. The aim of this study was to evaluate the rate of recurrence and outcome of autoimmune hepatitis after transplantation. METHODS The records of patients transplanted in eight centers in our country between 1984 and 1996 were retrospectively analyzed. RESULTS Forty-three of the 2331 (1.8%) recipients fulfilled diagnostic criteria of autoimmune hepatitis at the time of transplantation. Sixteen patients were excluded from evaluation. Nine (33%) of the 27 patients evaluated fulfilled criteria for recurrence of autoimmune hepatitis, with a mean time of recurrence after orthotopic liver transplantation of 2.6+/-1.5 years. Patients with recurrence had a longer follow-up time after transplantation (5.1 vs. 2.5 years, P=0.0012) and were receiving less immunosuppressive treatment. The estimated risk of recurrence of autoimmune hepatitis in the graft increased over time: 8% over the first year and 68% 5 years after transplantation. None of the seven patients with liver-kidney microsomal-positive antibodies recurred (P=0.059). Fifty percent of the patients failed to respond or responded only partially to therapy, although none of the patients have deteriorated clinically after 2.4+/-1.06 years of follow-up after recurrence. CONCLUSIONS Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced. Although response to treatment is poor, patient and graft survival do not appear to be decreased.

Variceal ligation compared with endoscopic sclerotherapy for variceal hemorrhage: prospective randomized trial.

BACKGROUND To evaluate the safety and efficiency of variceal ligation compared with endoscopic sclerotherapy, 88 patients with cirrhosis with recent variceal bleeding were randomized to undergo either treatment. METHODS Sclerotherapy was performed using ethanolamine and polidocanol injection at 1, 2, and 3 weeks and every 3 weeks thereafter. The Stiegmann-Goff device was used for variceal ligation at the same intervals. RESULTS The rate of variceal eradication was the same for both groups, but eradication was accomplished sooner in patients undergoing variceal ligation (5.3+/-1.6 vs. 6.6+/-2.4 endoscopic sessions, p < 0.05) and with fewer complications (19 vs. 6, p < 0.005). The rate of recurrent bleeding was lower in patients treated by ligation (31% vs. 50%, p < 0.05). After eradication, variceal recurrence was more frequent in patients treated by variceal ligation at 1 and 3 years (47% and 92% vs. 23% and 55%, p < 0.01). Portal hypertensive gastropathy was significantly worse in the patients who had variceal ligation (17 patients vs. 6, p < 0.01). Survival and treatment failure were similar in both groups. CONCLUSIONS Variceal ligation was superior to sclerotherapy in terms of the rate of recurrent bleeding and the occurrence of complications but worse with respect to recurrence of varices and the evolution of portal hypertensive gastropathy. Long-term follow-up studies are required to find out whether there are deleterious effects of variceal ligation.

Plasma Leptin and TNF-α Levels in Chronic Hepatitis C Patients and Their Relationship to Hepatic Fibrosis

The aim of this study was to examine the possible relationship between the plasma levels of leptin and tumor necrosis factor (TNF)-α and the stage of hepatic fibrosis in a cohort of patients with chronic hepatitis C. Leptin and TNF levels were measured by RIA in 135 patients and in 75 age- and sex-matched controls. Liver disease was evaluated by the stage of fibrosis and the extent of inflammatory infiltrate in the liver biopsy. Leptin levels correlated with BMI values in healthy controls and in patients with chronic hepatitis C (men, r = 0.61, P = 0.0001; women, r = 0.68, P = 0.003). Leptin levels increased as hepatic fibrosis stage progressed both in male and in female patients (P < 0.001); also, TNF levels were higher in patients with an advanced stage of fibrosis (P = 0.006). In these patients, levels of leptin increased according to the progression of the stage of fibrosis; these data suggest that leptin may play a role in the regulation of hepatic fibrosis.

Liver Transplantation in a Case of Steatohepatitis and Subacute Hepatic Failure after Biliopancreatic Diversion for Morbid Obesity

Background: Biliopancreatic diversion (BPD) was designed to avoid the serious complications of jejunoileal bypass (steatohepatitis and hepatic failure). Although this is today considered a safe and effective procedure, a few reports of patients who developed steatohepatitis and subsequently died in hepatic failure exist. Methods: We report a morbidly obese patient who developed subacute hepatitis resulting in hepatic failure 1 year after BPD. Results: Because of irreversible liver failure the decision to perform a liver transplantation was made.The patient underwent emergency liver transplant and lengthening of the common limb. The course of liver transplantation and the patients recovery were uneventful. Conclusion: Severe liver disease may rarely follow BPD. Liver transplantation and lengthening of the common bowel may be performed to treat these patients.

Changes in the Serum Levels of Interleukin-17/ Interleukin-23 During Acute Rejection in Liver Transplantation

Interleukin‐23 (IL‐23) and T helper 17 (Th17) cells have been cast as major players in autoimmunity, but their role in transplantation immunity remains to be specified. The aim of our study was to investigate the time course of serum levels of IL‐23 and IL‐17 during hepatic allograft rejection. Serum levels of IL‐23 and IL‐17 were determined in 20 healthy subjects and 50 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 35 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL‐23 were similar for the rejection group and nonrejection group at early postoperative times. We observed a significant increase in serum IL‐23 levels in the rejection group when a diagnosis of acute rejection had been established. Similarly to IL‐23, at the diagnosis of acute rejection, the concentration of IL‐17 was significantly higher in the rejection group versus the nonrejection group. The whole transplant group, including those with stable graft function, had higher serum levels of IL‐23 and IL‐17 than the controls during the entire postoperative period. In conclusion, IL‐23 and IL‐17 are up‐regulated during acute hepatic rejection. These findings suggest a role for Th17 cells in human liver allograft rejection. Liver Transpl 15:629–633, 2009.

ImmuKnow as a diagnostic tool for predicting infection and acute rejection in adult liver transplant recipients: A systematic review and meta‐analysis

Immune status monitoring of transplant recipients could identify patients at risk of acute rejection, infection, and cancer, which are important sources of morbidity and mortality in these patients. The ImmuKnow assay provides an objective assessment of the cellular immune function of immunosuppressed patients. Inconclusive results concerning the ability of the ImmuKnow test to predict acute rejection and infection have raised concerns about the predictive value of ImmuKnow in liver transplant recipients. We conducted a systematic literature review to identify studies published up to March 2012 that documented the use of ImmuKnow for monitoring immune function in liver transplant recipients. The study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 score. We identified 5 studies analyzing ImmuKnow performance for infection and 5 studies analyzing ImmuKnow performance for acute rejection. The pooled sensitivity, specificity, positive likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 83.8% [95% confidence interval (CI) = 78.5%‐88.3%], 75.3% (95% CI = 70.9%‐79.4%), 3.3 (95% CI = 2.8‐4.0), 14.6 (95% CI = 9.6‐22.3), and 0.824 ± 0.034, respectively, for infection and 65.6% (95% CI = 55.0%‐75.1%), 80.4% (95% CI = 76.4%‐83.9%), 3.4 (95% CI = 2.4‐4.7), 8.8 (95% CI = 3.1‐24.8), and 0.835 ± 0.060, respectively, for acute rejection. Heterogeneity was low for infection studies and high for acute rejection studies. In conclusion, the ImmuKnow test is a valid tool for determining the risk of further infection in adult liver transplant recipients. Significant heterogeneity across studies precludes the conclusion that ImmuKnow identifies liver transplant patients at risk for rejection. Liver Transpl 18:1245–1253, 2012.

Vitamin D deficiency in chronic liver disease.

Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis, but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation, has immunomodulatory and anti-inflammatory properties. Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) virus infection. The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known, but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases. Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease. Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

Osteoprotegerin and RANKL in alcoholic liver cirrhosis.

Abstract: Background/aims: The mechanisms leading to osteoporosis in alcoholic liver disease remain poorly understood. Recently identified soluble circulating osteoprotegerin (OPG), is the osteoclastogenesis inhibitory factor. It acts as a decoy receptor for osteoclast activating factor, receptor activator of nuclear factor‐κB ligand (RANKL), and impairs osteoclast function. The aim of our study was to investigate the OPG/RANKL system in alcoholic cirrhotic patients and their correlation with biochemical marker of bone turnover.

Long-term survival after liver transplantation for alcoholic liver disease

Currently, alcoholic cirrhosis is the second leading indication for liver transplantation in the United States and Europe. The quality of life and survival after a liver transplantation (LT) in patients with alcoholic liver disease (ALD) are similar to those in patients with other cirrhosis etiologies. The alcoholic relapse rate after a LT varies from 10%-50%, and these relapse patients are the ones who present a reduced long-term survival, mainly due to cardiovascular diseases and the onset of de novo neoplasms, including lung and upper aerodigestive tract. Nearly 40% of ALD recipients resume smoking and resume it early post-LT. Therefore, our pre-and post-LT follow-up efforts regarding ALD should be focused not only on alcoholic relapse but also on treating and avoiding other modifiable risk factors such as tobacco. The psychiatric and psychosocial pre-LT evaluation and the post-LT follow-up with physicians, psychiatrists and addiction specialists are important for reversing these problems because these professionals help to identify patients at risk for relapse as well as those patients who have relapsed, thus enabling responsive actions.