Michele Molinari

Metabolic syndrome in liver transplant recipients: Prevalence and association with major vascular events

Cardiac and cerebral vascular diseases are leading causes of morbidity and death in solid organ transplant recipients. Immunosuppressant drugs are associated with dyslipidemia, hypertension, and hyperglycemia, which along with obesity are the main features of metabolic syndrome. In the nontransplant population, metabolic syndrome is associated with increased risk for major vascular complications. We postulated that metabolic syndrome is common post–liver transplantation and plays a significant role leading to cardiac and cerebrovascular events. Our Multi‐Organ Transplant Program database was reviewed for all liver transplant recipients between January 1998 and June 2004 with follow‐up until December 2005. We adapted the 2001 National Cholesterol Education Program‐Adult Treatment Panel III Guidelines to define posttransplantation metabolic syndrome (PTMS) as the presence at least 3 of the following: 1) obesity (body mass index >30 kg/m2); 2) serum triglyceride level ≥1.7 mmol/L; 3) high density lipoprotein level <1 mmol/L in men and <1.3 mmol/L in women; 4) hypertension; and 5) fasting plasma glucose ≥5.6 mmol/L. A total of 118 patients were included. Among them, 69 patients (58%) had PTMS. The mean (± standard deviation) time from transplant was 59 ± 21 months (no significant difference in patients with or without metabolic syndrome). Overall, patients with metabolic syndrome had a significantly higher average age, posttransplantation body mass index, fasting glucose, high‐density lipoprotein levels, and serum triglycerides. There was no difference in creatinine, hemoglobin, or prednisone average dose between the 2 groups. There were 25 major vascular events affecting 21% of patients. There were significantly more vascular events in patients with metabolic syndrome posttransplantation than in those without (30% vs. 8%; P = 0.003) during the study period. In conclusion, the prevalence of metabolic syndrome post–liver transplant is significantly higher than that estimated in the general population. Metabolic syndrome appears to be associated with an increased risk of major vascular events in our liver transplant population. Liver Transpl 13:1109–1114, 2007.

Evidence-Based Approach to Cholangiocarcinoma: A Systematic Review of the Current Literature

adjusted mortality rate increased from 0.07 per 100,000 in 1973 to 0.69 per 100,000 in 1997, with average age at presentation in the 7th decade of life and male-to-female ratio of 1.5. 9 Extrahepatic CC In the United States, age-adjusted incidence of extrahepatic CC (ECC) is 1.2 per 100,000 in men and 0.8 per 100,000 in women 10 and has decreased by 14% compared with two decades earlier. ECC usually present in the 7th decade of life.

Acute liver failure induced by green tea extracts: Case report and review of the literature

In industrialized countries, over‐the‐counter dietary supplements have become popular in preventing and treating an expanding list of medical conditions. Although most commercially available supplements have not been rigorously tested for safety and efficacy, they have found an enlarging market because they are considered natural. Oral supplements containing green tea extract have been marketed as effective for weight loss and to prevent and cure some solid tumors. Although there is little scientific evidence of the effectiveness of green tea extracts to improve the quality of health of regular consumers, there is an increasing body of medical literature supporting the hypothesis that they can cause serious side effects. Our experience adds to previous reports of acute liver toxicity observed in individuals consuming supplements containing green tea extract. We highlight the importance of obtaining a detailed history of dietary supplement consumption when evaluating a patient presenting with acute liver dysfunction. Liver Transpl 12:1892–1895, 2006.

Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic.

Living-Donor Right Hepatectomy with or without Inclusion of Middle Hepatic Vein: Comparison of Morbidity and Outcome in 56 Patients

Venous congestion of segments V and VIII is observed frequently in living‐donor right lobe liver transplants without middle hepatic vein (MHV) drainage, and can be a cause of graft dysfunction and failure. Inclusion of the MHV with the graft is controversial, however, because of the perceived potential for increased donor morbidity.

Hepatic resection versus radiofrequency ablation for hepatocellular carcinoma in cirrhotic individuals not candidates for liver transplantation: A Markov model decision analysis

BACKGROUND Several observational studies have suggested that radiofrequency ablation (RFA) may have survival benefits similar to hepatic resection (HR) in cirrhotic patients affected by hepatocellular carcinoma (HCC) are not candidates for liver transplantation. A small randomized controlled trial confirmed these findings, although underpowered to detect a significant difference at 5-year interval. METHODS A Markov model was created to simulate a randomized trial comparing the quality of life-adjusted survival for individuals undergoing HR versus RFA for HCCs less than 5 cm in diameter. RESULTS HR was the best therapeutic option with 5.33 (standard deviation +/-.42) versus 3.91 (standard deviation +/-.38) quality-adjusted life years except for in individuals older than 75 years of age (P = .02, log rank test). One-way sensitivity analysis showed that RFA was the preferred strategy if the perioperative mortality of HR was more than 30%, if the percentage of patients with negative margins was less than 60%, and if RFA could be performed at least 60% of the time for recurrent disease after a previous ablation. The quality of life associated with both procedures did not influence the results of this model. CONCLUSIONS HR provided better quality of life-adjusted survival as ablation therapy was associated with increased risk of local recurrent disease requiring multiple sessions. For older individuals, RFA appears to be the best therapeutic option. If the probability of ablation for recurrent disease is equal in the 2 arms, survival benefits of RFA is similar to HR.

Rifaximin vs conventional oral therapy for hepatic encephalopathy: A meta-analysis

AIM To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS We performed a systematic review and random effects meta-analysis of all eligible trials identified through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics [odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profile (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical significance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any significant difference in the above findings. CONCLUSION Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profile.

Consensus Statements From a Multidisciplinary Expert Panel on the Utilization and Application of a Liver-Specific MRI Contrast Agent (Gadoxetic Acid)

OBJECTIVE. This systematic review presents evidence-based consensus statements as reported by a multidisciplinary expert panel (six abdominal radiologists, four hepatobiliary surgeons, and two hepatologists) regarding the use of gadoxetic acid for liver MRI. CONCULSION. Although this review highlights the incremental diagnostic value of hepatobiliary phase imaging with gadoxetic acid-enhanced liver MRI in multiple clinical scenarios, there remains a need for further impact studies for some clinical applications, such as hepatocellular carcinoma in cirrhosis.

Role of Magnetic Resonance Cholangiography in Assessing Biliary Anatomy in Right Lobe Living Donors

Background. The value of magnetic resonance cholangiography (MRC) in assessing potential adult-to-adult living liver transplant (ALDLT) donors remains poorly defined. The purpose of this study is to determine the accuracy of MRC in assessing biliary anatomy with intraoperative confirmation. Methods. A prospective cohort of 30 ALDLT donors who underwent right hepatectomy from October 2000 to July 2003 was evaluated. MRC was performed using a heavily T2 weighted radial slab technique. MRC was interpreted preoperatively by a radiologist and a surgeon and compared with the intraoperative biliary findings in all patients derived from cholangiography (IOC) and bile duct exploration. The sensitivity, specificity, and positive and negative predictive values of MRC for aberrant biliary anatomy were calculated. Results. MRC suggested normal, aberrant, and indeterminate biliary anatomy in 16, 12, and 2 donors, respectively. IOC revealed normal and aberrant biliary anatomy in 17 and 13 patients, respectively. MRC demonstrated biliary anatomy accurately in 27 of 30 patients. The sensitivity, specificity, positive predictive, and negative predictive values of MRC in detecting aberrant biliary anatomy were 92%, 100%, 100%, and 94%, respectively. Conclusions. Preoperative MRC accurately depicts biliary anatomy in potential ALDLT donors and may guide the intraoperative management of the biliary tract.

Safety and effectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia

Hypercholesterolemia is a common problem among transplant recipients. Despite package‐insert warnings about the potential side effects of the use of statins in patients with chronic liver disease, they are often prescribed for liver transplant recipients. Unlike statins, ezetimibe acts through inhibition of enterohepatic recirculation of lipids. We report the effectiveness and safety of ezetimibe among liver transplant recipients because this has been evaluated previously only in kidney and heart transplant patients. A consecutive cohort of 25 liver graft recipients with serum low‐density lipoprotein (LDL) levels > 100 mg/dL (2.5 mmol/L) after a mean (±standard deviation) of 55 ± 21 months following liver transplantation received ezetimibe (10 mg orally every day) for at least 6 months. Serum lipid profiles, liver and renal function tests, and dosages and blood levels of the immunosuppression drugs at baseline, 3 months, and 6 months were prospectively collected. The overall mean age was 58 ± 12 years, and 56% were males. Statin therapy and fibrates were already being used in 32% and 20% of recipients for elevated LDL and/or triglycerides, respectively. The immunosuppression regimen included cyclosporine in 48% of subjects, tacrolimus in 32%, sirolimus in 48%, and mycophenolate mofetil in 44%; only 12% were on oral prednisone with a maximum daily dose of 5 mg. After ezetimibe was started, an 18% reduction in LDL values was observed [at baseline, 147 ± 35 mg/dL (3.8 ± 0.9 mmol/L), and at 6 months, 120 ± 31 mg/dL (3.1 ± 0.8 mmol/L); P = 0.010]. After 6 months, an additional 32% achieved the target LDL level of <100 mg/dL. None of the remaining variables, including immunosuppression drug levels, varied significantly during ezetimibe therapy. None of the subjects required adjustments in their pharmacological dosages. One discontinued ezetimibe 3 months later because of cost, 2 subjects had minimal nausea, 1 subject had myalgias without a rise in creatine phosphokinase, and 1 subject had a transient elevation (3‐5 times) in liver enzymes from baseline with increases in the total and indirect bilirubin levels. In conclusion, among liver transplant recipients, hypercholesterolemia can be effectively treated with ezetimibe with few side effects and no interaction with immunosuppressive regimens. Liver Transpl 15:504–508, 2009.