Nicola Venturoli

What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy

BACKGROUND/AIMS/METHODS The diagnosis of cirrhosis is currently based on percutaneous liver biopsy, although this procedure may give rise to false negative results. This prospective study blindly investigates the accuracy of an ultrasonographic score, derived from liver, spleen and portal vein features, in predicting the final diagnosis in 212 patients with compensated chronic liver disease undergoing percutaneous liver biopsy. RESULTS Taking biopsy as the standard, the ultrasonographic score differed significantly between chronic hepatitis (39+/-33) and cirrhosis (100+/-35) (p<0.0001). Discriminant analysis with stepwise forward selection of the variables identified liver surface nodularity and portal flow velocity as independently associated with the diagnosis of cirrhosis (p<0.005), and a score based on these two variables correctly identified cirrhosis in 82.2% of cases. One or both of these abnormalities were also found in 27/32 patients who were diagnosed as having cirrhosis at ultrasound, but were not cirrhotic histologically. Eight of these 32 cases developed signs of decompensated liver disease and/or portal hypertension in the subsequent 6-month follow-up, thus supporting the diagnosis of cirrhosis. CONCLUSIONS Our data suggest that ultrasound is accurate in predicting the final diagnosis in patients with compensated chronic liver disease and may identify cirrhosis even in the absence of a typical histopathological pattern. However, neither percutaneous liver biopsy nor ultrasonography can be assumed to be the definitive criterion for the diagnosis of compensated cirrhosis.

Laboratory test variability and model for end-stage liver disease score calculation: effect on liver allocation and proposal for adjustment.

Background. The use of the Model for End-Stage Liver Disease (MELD) score to prioritize patients on liver waiting lists must take the bias of different laboratories into account. Methods. We evaluated the outcome of 418 patients listed during 1 year whose MELD score was computed by two laboratories (lab 1 and lab 2). The two labs had different normality ranges for bilirubin (maximal normal value [Vmax]: 1.1 for lab 1 and 1.2 for lab 2) and creatinine (Vmax: 1.2 for lab 1 and 1.4 for lab 2). The outcome during the waiting time was evaluated by considering the liver transplantations and the dropouts, which included deaths on the list, tumor progression, and patients who were too sick. Results. Although the clinical features of patients were similar between the two laboratories, 36 (13.1%) out of 275 were dropped from the list in lab 1, compared to 5 (3.5%) out of 143 in lab 2 (P<0.01). The differences were mainly due to the deaths on the list (8% lab 1 vs. 2.1% lab 2, P<0.05). The competing risk analysis confirmed the different risk of dropout between the two labs independently of the MELD score, blood group, and preoperative diagnosis. The bias on MELD calculation was considered and bilirubin and creatinine values were “normalized” to Vmax of lab 1 (corrected value=measured value×Vmax lab 1/Vmax lab 2). By comparing receiver operating characteristic curves, the ability of MELD to predict the 6-month dropouts significantly increased from an area under the curve of 0.703 to 0.716 after “normalization” (P<0.05). Conclusions. Normalization of MELD is a correct and good compromise to avoid systematic bias due to different laboratory methods.

A multiorgan donor cancer screening protocol: the Italian Emilia-Romagna region experience.

Background. We describe the Emilia-Romagna screening protocol for all multiorgan donors within this region of Italy and report on the first 2 years of implementation. Setting. Setting is a 24-hour multidisciplinary call service covering the 16 intensive care units in Emilia-Romagna (3,969,000 inhabitants) and a centralised pathology center, directed by a transplant coordination center. Study Population and Period. All 271 effective donor candidates presenting in Emilia-Romagna in 2001–2002. Protocol. Anamnesis, external examination, and thorough laboratory and instrumental screening is followed by sampling of internal effusions and evaluation of all internal organs. All suspect findings are then investigated by extemporary pathologic evaluation. To fit national legal requirements, candidates are classified as standard risk (no transmissible risk); nonstandard risk (low-risk of transmission, eligibility restricted to certified clinical emergencies pending informed consent); and unacceptable risk (unconditional exclusion because of high-risk pathologies). Results. The protocol was successfully implemented for all 271 candidates. In addition to 14 independent exclusions, clinical suspicion of cancer was raised for 61 donors presenting with 82 lesions or effusions. Along with one case of lymph-node tuberculosis (unacceptable risk), histocytologic screening revealed eight cases of malignancy (5 prostate, 1 papillary-thyroid, 1 follicular-thyroid, and 1 renal cell, all nonstandard risk); the remainder were benign (standard risk). Protocol implementation led to exclusion of 8 (3.0%) candidates (1 nonstandard risk transplantation was performed). Conclusions. This stringent protocol—now adopted with some modifications at a national level—provides an initial example of a feasible intervention aimed at maximising donation safety while rationalizing use of marginal donors.

Folate-related polymorphisms in gastrointestinal stromal tumours: susceptibility and correlation with tumour characteristics and clinical outcome

The folate metabolism pathway has a crucial role in tumorigenesis as it supports numerous critical intracellular reactions, including DNA synthesis, repair, and methylation. Despite its importance, little is known about the influence of the folate pathway on gastrointestinal stromal tumour (GIST), a rare tumour with an incidence ranging between 6 and 19.6 cases per million worldwide. The importance of folate metabolism led us to investigate the influence of polymorphisms in the genes coding folate-metabolising enzymes on GIST susceptibility, tumour characteristics and clinical outcome. We investigated a panel of 13 polymorphisms in 8 genes in 60 cases and 153 controls. The TS 6-bp deletion allele (formerly rs34489327, delTInsTTAAAG) was associated with reduced risk of GIST (OR=0.20, 95% CI 0.05–0.67, P=0.0032). Selected polymorphisms in patients stratified by age, gender, and other main molecular and clinical characteristics showed that few genotypes may show a likely correlation. We also observed a significant association between the RFC AA/AG genotype and time to progression (HR=0.107, 95% CI 0.014–0.82; P=0.032). Furthermore, we observed a tendency towards an association between the SHMT1 variant allele (TT, rs1979277) and early death (HR=4.53, 95% CI 0.77–26.58, P=0.087). Aware of the strengths and limitations of the study, these results suggest that polymorphisms may modify the risk of GIST and clinical outcome, pointing to the necessity for further investigations with information on folate plasma levels and a larger study population.

A comparison of pedriatric and adult kidney donors for adult recipients

The high demand for organs for transplantation has made it necessary to consider using even the oldest and youngest of potential donors in order to increase the organ supply. In this retrospective study, the outcome of kidney transplantation using cadaveric pediatric donors was compared with that of an adult control series. Graft procurement took place in two regions of Italy (Emilia‐Romagna and Piemonte) over an 11‐year period. A group of pediatric donors (<15 years old, n = 30) was compared with an adult donor group (n= 67). All recipients were adults who received cyclosporin as immunosuppression. Actuarial patient and graft survival rates did not differ significantly between the two groups (patient survival 96 % and 96 % for pediatric donors versus 98 % and 92 % for adult donors at 1 and 5 years post‐transplantation; graft survival 76 % and 68 % for pediatric donors versus 88 % and 74 % for adult donors 1 and 5 y post‐transplantation). Complications were also evaluated, but no difference was found (the only exception being the creatinine level in the 5th year). Renal transplantation with cadaveric donors starting at 4 years of age gave results comparable to kidneys coming from adults. These data show that cadaveric pediatric donor kidneys may be used in adult recipients with good results. The ethical implications of the subject are extensively reviewed.