Salvatore Gruttadauria

Hepatic echinococcosis: Clinical and therapeutic aspects

Echinococcosis or hydatid disease (HD) is a zoonosis caused by the larval stages of taeniid cestodes belonging to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated into alveolar and cystic forms, associated with Echinoccus multilocularis (E. multilocularis) and Echinococcus granulosus (E. granulosus) infection, respectively. Cystic echinococcosis (CE) has a worldwide distribution, while hepatic alveolar echinococcosis (AE) is endemic in the Northern hemisphere, including North America and several Asian and European countries, like France, Germany and Austria. E. granulosus young cysts are spherical, unilocular vesicles, consisting of an internal germinal layer and an outer acellular layer. Cyst expansion is associated with a host immune reaction and the subsequent development of a fibrous layer, called the pericyst; old cysts typically present internal septations and daughter cysts. E. multilocularis has a tumor-like, infiltrative behavior, which is responsible for tissue destruction and finally for liver failure. The liver is the main site of HD involvement, for both alveolar and cystic hydatidosis. HD is usually asymptomatic for a long period of time, because cyst growth is commonly slow; the most frequent symptoms are fatigue and abdominal pain. Patients may also present jaundice, hepatomegaly or anaphylaxis, due to cyst leakage or rupture. HD diagnosis is usually accomplished with the combined use of ultrasonography and immunodiagnosis; furthermore, the improvement of surgical techniques, the introduction of minimally invasive treatments [such as puncture, aspiration, injection, re-aspiration (PAIR)] and more effective drugs (such as benzoimidazoles) have deeply changed life expectancy and quality of life of patients with HD. The aim of this article is to provide an up-to-date review of biological, diagnostic, clinical and therapeutic aspects of hepatic echinococcosis.

Efficacy and Safety of Fully Covered Self- Expandable Metallic Stents in Biliary Complications After Liver Transplantation: A Preliminary Study

After liver transplantation, the most common biliary complication is the anastomotic stricture, which is followed by biliary leakage. Studies have focused on the endoscopic treatment of biliary complications in transplanted patients with duct‐to‐duct reconstruction, showing a success rate of 70% to 80% after orthotopic liver transplantation and of 60% after living‐related liver transplantation. Once the endoscopic approach fails, surgical treatment with a Roux‐en‐Y choledochojejunostomy is the sole alternative treatment. The aim of this prospective observational study was to analyze the efficacy and safety of fully covered self‐expandable metallic stents for the treatment of posttransplant biliary stenosis and leaks in patients in whom conventional endoscopic retrograde cholangiopancreatography (ERCP) failed. From January 2008 to January 2009, 16 patients met the criteria of endoscopic treatment failure, and instead of surgery, a fully covered stent was placed. All patients had at least 6 months of follow‐up (mean follow‐up of 10 months). After removal, 14 patients showed immediate resolution of both the biliary stenosis and leak. After a mean of 10 months of follow‐up, only 1 patient showed biliary stenosis recurrence. No major complications occurred in any of the patients, except for stent migration in 6 patients, although these presented with no clinical consequences. In conclusion, in patients not responding to standard endoscopic treatment, the placement of fully covered metal stents is a valid alternative to surgery. A cost analysis should be performed in order to evaluate whether to treat transplanted patients suffering from biliary complications with covered self‐expandable metallic stent placement as first‐line therapy. Liver Transpl 15:1493–1498, 2009.

Worldwide epidemiology of liver hydatidosis including the Mediterranean area

The worldwide incidence and prevalence of cystic echinococcosis have fallen dramatically over the past several decades. Nonetheless, infection with Echinococcus granulosus (E. granulosus) remains a major public health issue in several countries and regions, even in places where it was previously at low levels, as a result of a reduction of control programmes due to economic problems and lack of resources. Geographic distribution differs by country and region depending on the presence in that country of large numbers of nomadic or semi-nomadic sheep and goat flocks that represent the intermediate host of the parasite, and their close contact with the final host, the dog, which mostly provides the transmission of infection to humans. The greatest prevalence of cystic echinococcosis in human and animal hosts is found in countries of the temperate zones, including several parts of Eurasia (the Mediterranean regions, southern and central parts of Russia, central Asia, China), Australia, some parts of America (especially South America) and north and east Africa. Echinococcosis is currently considered an endemic zoonotic disease in the Mediterranean region. The most frequent strain associated with human cystic echinococcosis appears to be the common sheep strain (G1). This strain appears to be widely distributed in all continents. The purpose of this review is to examine the distribution of E. granulosus and the epidemiology of a re-emerging disease such as cystic echinococcosis.

Liver Transplantation for Neuroendocrine Tumors in Europe—Results and Trends in Patient Selection A 213-Case European Liver Transplant Registry Study

Objective:The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. Background:LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. Methods:This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1–149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. Results:Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. Conclusions:LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

The hepatic artery in liver transplantation and surgery: vascular anomalies in 701 cases

The purpose of this study is to report the variations in hepatic arterial supply of a mixed population of organ donors in which the anatomy was individually examined during the bench surgery, and patients who underwent a selective angiogram of the celiac axis and superior mesenteric artery. 
We reviewed the donor forms and/or angiograms of 701 patients. The donor forms were completed personally by one of the authors, while all the radiology images were obtained through studies performed by one single radiologist. The arterial anatomy was anomalous in 296 out of 701 cases with an overall incidence of hepatic artery anomalies of 42.22%. 
In this paper we describe previously unreported arterial anomalies of the hepatic artery, collecting the second largest series of hepatic artery anatomical variations of the English literature. This anatomical update can be useful for transplant and general surgeons, as well as vascular radiologists.

Mediterranean Diet and Cardiovascular Risk Factors: A Systematic Review

The aim of this paper was to systematically review and analyze the epidemiological evidence on the role of Mediterranean diet (MD) in the prevention of cardiovascular diseases (CVD). Fifty-eight studies exploring the relation between MD and lipoprotein concentration, antioxidative capacity and inflammatory markers, hypertension, obesity, diabetes, and metabolic syndrome, were identified and selected. These included 33 cross-sectional, 9 cohort, and 16 intervention studies. Most of the studies showed favorable effects of MD on CVD, although a certain degree of controversy remains in the respect of some issues, as obesity. Important methodological differences and limitations in the studies make difficult to compare results, thus further studies, particularly randomized clinical trials, are needed to finally substantiate the benefits of MD and to shed some lights on mechanisms.

Liver biopsy findings from healthy potential living liver donors: Reasons for disqualification, silent diseases and correlation with liver injury tests

BACKGROUND/AIMS Liver biopsies detect silent donor disease in potential living liver donors and provide material for studies of subclinical non-alcoholic fatty liver disease (NAFLD). Our primary goal was to determine the contribution of biopsy findings to potential donor evaluation. Factors contributing to pre-clinical NAFLD and correlations between liver injury tests and histopathology have been also determined. METHODS Patient records, laboratory tests and results of the histopathologic examination and diagnoses of 284 patients from 2001 to 2005 were retrospectively extracted from the EDIT database. Hepatic histology was correlated with liver injury tests and with general demographic characteristics in an otherwise normal healthy population. RESULTS A minority (n=119; 42%) of biopsies from this population of 143 males/141 females (average age=36.8years; mean BMI=26.6) were completely normal. The remainder showed steatosis (n=107; 37%), steatohepatitis (n=44; 15%), or unexplained low-grade/early stage chronic hepatitis, primary biliary cirrhosis, or nodular regenerative hyperplasia (n=16; 6%). Biopsy findings disqualified 29/56 donors. Independent risk factors for NAFLD by multivariate modeling, which differed by sex, included: BMI (p=0.0001), age (p=0.003), iron (p=0.01), and ALT (p=0.004). CONCLUSIONS Liver biopsies provide valuable information about otherwise undetectable liver disease in potential liver donors. Obesity, age and iron, which are influenced by sex, contribute to NAFLD pathogenesis. Blood tests other than standard liver profiles are needed to detect early NAFLD.

Balancing Donor and Recipient Risk Factors in Liver Transplantation: The Value of D‐MELD With Particular Reference to HCV Recipients

Donor–recipient match is a matter of debate in liver transplantation. D‐MELD (donor age × recipient biochemical model for end‐stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3‐year patient survival. D‐MELD cutoff predictive of 5‐year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D‐MELD.com). Differences among D‐MELD deciles allowed their regrouping into three D‐MELD classes (A < 338, B 338–1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44–2.85) in D‐MELD class C versus B. The OR was 0.40 (95% CI, 0.24–0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11–1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51–0.93), retransplant (OR = 1.82; 95% CI, 1.16–2.87) and low‐volume center (OR = 1.48; 95% CI, 1.11–1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59–2.43) for D‐MELD class C versus class B and 0.42 (95% CI, 0.29–0.60) for D‐MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D‐MELD ≥ 1750). The innovative approach offered by D‐MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell–based therapy and case report on cell transplantation

Although hepatic cell transplantation (CT) holds the promise of bridging patients with end‐stage chronic liver failure to whole liver transplantation, suitable cell populations are under debate. In addition to hepatic cells, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being considered as alternative cell sources for initial clinical cell work. Fetal liver (FL) tissue contains potential progenitors for all these cell lineages. Based on the collagenase incubation of tissue fragments, traditional isolation techniques yield only a fraction of the number of available cells. We report a 5‐step method in which a portal vein in situ perfusion technique is used for tissue from the late second trimester. This method results in the high viabilities known for adult liver vascular perfusion, addresses the low cell yields of conventional digestion methods, and reduces the exposure of the tissue to collagenase 4‐fold. We used donated tissue from gestational weeks 18 to 22, which yielded 1.8 ± 0.7 × 109 cells with an average viability of 78%. Because HSC transplantation and MSC transplantation are of interest for the treatment of hepatic failure, we phenotypically confirmed that in addition to hepatic progenitors, the resulting cell preparation contained cells expressing typical MSC and HSC markers. The percentage of FL cells expressing proliferation markers was 45 times greater than the percentage of adult hepatocytes expressing these markers and was comparable to the percentage of immortalized HepG2 liver hepatocellular carcinoma cells; this indicated the strong proliferative capacity of fetal cells. We report a case of human FL CT with the described liver cell population for clinical end‐stage chronic liver failure. The patients Model for End‐Stage Liver Disease (MELD) score improved from 15 to 10 within the first 18 months of observation. In conclusion, this human FL cell isolation protocol may be of interest for further clinical translation work on the development of liver cell–based therapies. Liver Transpl 18:226–237, 2012.

Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system

Abstract:  Coagulopathy is a life‐threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell‐free dialysis technique, on the blood coagulation of cirrhotic patients.