Laura Marelli

A systematic review of the performance of the model for end-stage liver disease (MELD) in the setting of liver transplantation.

The Model for End‐Stage Liver Disease (MELD) score is now used for allocation in liver transplantation (LT) waiting lists, replacing the Child‐Turcotte‐Pugh (CTP) score. However, there is debate as whether it is superior to CTP score to predict mortality in patients with cirrhosis on the LT waiting list and after LT. We reviewed studies comparing the accuracy of MELD vs. CTP score in transplantation settings. We found that in studies of the LT waiting list (12,532 patients with cirrhosis), only 4 of 11 showed MELD to be superior to CTP in predicting short‐term (3‐month) mortality. In addition, 2 of 3 studies (n = 1,679) evaluating the changes in MELD score (ΔMELD) showed that ΔMELD had better prediction for mortality than the baseline MELD score. The impact of MELD on post‐LT mortality was assessed in 15 studies (20,456 patients); only 6 (9,522 patients) evaluated the discriminative ability of MELD score using the concordance (c) statistic (the MELD score had always a c‐statistic < 0.70). In 11 studies (19,311 patients), high MELD score indicated poor post‐LT mortality for cutoff values of 24‐40 points. In re‐LT patients, 2 of 4 studies evaluated the discriminative ability of MELD score on post‐LT mortality. Finally, several studies have shown that the predictive ability of MELD score increases by adding clinical variables (hepatic encephalopathy, ascites) or laboratory (sodium) parameters. On the basis of the current literature, MELD score does not perform better than the CTP score for patients with cirrhosis on the waiting list and cannot predict post‐LT mortality. Liver Transpl 12:1049–1061, 2006.

A Systematic Review of the Quality of Liver Biopsy Specimens

Characteristics for an optimal liver biopsy specimen were recently defined as 20 to 25 mm long and/or containing more than 11 complete portal tracts (CPTs). A systematic review of percutaneous liver biopsy (PLB) and transjugular liver biopsy (TJLB) series yielded only 32 PLB studies in which these characteristics were evaluated: mean +/- SD length, 17.7 +/- 5.8 mm and number of CPTs, 7.5 +/- 3.4; and 15 TJLB studies: mean +/- SD length, 13.5 +/- 4.5 mm and number of CPTs, 6.8 +/- 2.3. Studies of sampling heterogeneity and intraobserver and interobserver variability also used inadequate specimens by present standards. Only 11 (5.3%) of 207 therapeutic studies for chronic hepatitis B and C documented length and/or number of CPTs. Of the current 12 studies evaluating noninvasive fibrosis tests, only 8 documented length or number of CPTs, and only 1 documented length and number of CPTs. New studies are needed based on adequate liver biopsy samples to provide reliable estimation of grading and staging in chronic liver disease.

Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation

Liver transplantation (LT) is the only therapeutic option for end‐stage primary sclerosing cholangitis (PSC), but PSC can recur (rPSC) in some patients after LT. The aim of our study was to evaluate the risk factors associated with rPSC. Between 1989 and 2004, 69 patients receiving transplantation for PSC (42 male, mean age 41.9 yr). Clinical and laboratory data, activity/extension and treatment of ulcerative colitis (UC), post‐LT cytomegalovirus (CMV) infection, and immunosuppression were evaluated. Determination of rPSC was made by radiological and histological findings. Exclusion criteria were ABO blood group incompatibility, hepatic artery stenosis, and biliary strictures occurring in <3 months post‐LT. A total of 48 (70%) patients had PSC and UC pre‐LT. rPSC occurred in 7 of 53 (13.5%, 2 patients with de novo UC) who were alive 1 yr after LT and/or met inclusion/exclusion criteria: median 60 (4‐120) months. No patient without post‐LT UC had rPSC: 0 of 20 vs. 7 of 26 with post‐LT UC (P = 0.027). The multivariate logistic regression analysis showed that maintenance steroids for UC (>3 months) post‐LT was the only risk factor significantly associated with rPSC (P = 0.025). In conclusion, the presence of UC post‐LT, and the need for maintenance steroids post‐LT, which is an independent factor, are associated with rPSC. These findings could help elucidate a possible mechanism of PSC pathogenesis. Liver Transpl, 2007.

Review article: renal function assessment in cirrhosis - difficulties and alternative measurements.

Background  Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of serum creatinine in the model for end‐stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA.

A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer

Background The prognosis for patients with hepatocellular cancer (HCC) undergoing transarterial therapy (TACE/TAE) is variable. Methods We carried out Cox regression analysis of prognostic factors using a training dataset of 114 patients treated with TACE/TAE. A simple prognostic score (PS) was developed, validated using an independent dataset of 167 patients and compared with Child–Pugh, CLIP, Okuda, Barcelona Clinic Liver Cancer (BCLC) and MELD. Results Low albumin, high bilirubin or α-fetoprotein (AFP) and large tumour size were associated with a two- to threefold increase in the risk of death. Patients were assigned one point if albumin <36 g/dl, bilirubin >17 μmol/l, AFP >400 ng/ml or size of dominant tumour >7 cm. The Hepatoma arterial-embolisation prognostic (HAP) score was calculated by summing these points. Patients were divided into four risk groups based on their HAP scores; HAP A, B, C and D (scores 0, 1, 2 and >2, respectively). The median survival for the groups A, B, C and D was 27.6, 18.5, 9.0 and 3.6 months, respectively. The HAP score validated well with the independent dataset and performed better than other scoring systems in differentiating high- and low-risk groups. Conclusions The HAP score predicts outcomes in patients with HCC undergoing TACE/TAE and may help guide treatment selection, allow stratification in clinical trials and facilitate meaningful comparisons across reported series.

Expression of somatostatin and dopamine 2 receptors in neuroendocrine tumours and the potential role for new biotherapies.

Introduction: Somatostatin and dopamine receptors are both G-protein-coupled receptors. Somatostatin receptor (SSTR) expression in neuroendocrine tumours has been well characterised, and there is evidence of dopamine receptor expression in neuroendocrine tumours. In this study, we examined expression of D2R, SSTR-2 and SSTR-5 using immunohistochemistry in patients with neuroendocrine tumours. Methods: Consecutive samples of formalin-fixed paraffin-embedded tumour tissue were available from 56 patients with a histologically confirmed diagnosis of neuroendocrine tumour (NET). The study population was divided into low-grade (n = 29), intermediate-grade (n = 18) and high-grade NET (n = 9). Immunohistochemical evaluation was performed for the expression of SSTR-2a, SSTR-5 and D2 receptors (D2R). Results: Both SSTR-2 and SSTR-5 were expressed in 100% of low-grade, 94.4% of intermediate-grade and 66.7% of high-grade NET. D2R was expressed in 93.1% of low-grade, 77.8% of intermediate-grade and 44.4% of high-grade tumours. Co-expression of all 3 receptors was present in 93.1% of low-grade tumours. There was an inverse correlation of SSTR-2 (r = –0.380, p < 0.005) and SSTR-5 (r = –0.472, p < 0.0001) with tumour grade. D2R was positively correlated with SSTR-2 (r = 0.269, p = 0.041) and SSTR-5 (r = 0.267, p = 0.045). Also, D2R expression was inversely correlated with grade of tumour (r = 0.395, p = 0.006). Octreoscan correlated with SSTR-2, SSTR-5 and D2R expression. Conclusion: D2R is expressed in the majority of low and intermediate grade tumours. It is co-expressed with SSTR-2 and SSTR-5 in the majority of cases. The advent of new chimeric molecules that bind both somatostatin and dopamine receptors may provide a new therapeutic option in the management of neuroendocrine patients.

TACE versus TAE as therapy for hepatocellular carcinoma

Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.

Transarterial embolization as neo-adjuvant therapy pretransplantation in patients with hepatocellular carcinoma.

Neo‐adjuvant transarterial therapies are commonly used for patients with HCC in the waiting list for liver transplantation (LT) to delay tumour progression, however, their effectiveness is not well‐established. We studied the effect of pre‐LT transarterial therapies on post‐LT HCC recurrence, using the explanted liver histology to assess therapeutic efficacy and the predictors of response to these therapies.

Long-term results of patients with malignant carcinoid syndrome receiving octreotide LAR.

Background  Octreotide LAR is an established treatment for malignant carcinoid syndrome. However, studies with large number of patients and long follow‐up are lacking.

Transarterial Injection of 131I-Lipiodol, Compared with Chemoembolization, in the Treatment of Unresectable Hepatocellular Cancer

Transarterial chemoembolization (TACE) improves survival in patients with hepatocellular carcinoma (HCC) in whom curative therapies are not suitable. The aim of this study was to assess survival differences in patients with hepatic cirrhosis and unresectable HCC treated by 131I-lipiodol versus TACE or transarterial embolization (TAE). Methods: A retrospective study was performed on a cohort of 124 patients undergoing treatment for unresectable HCC between 1997 and 2006. A total of 50 patients (44 men; mean age, 59 y) received 131I-lipiodol (mean sessions per patient, 1.7), and 74 patients (63 men; mean age, 61 y) received TACE/TAE (mean sessions per patient, 1.8). Although no significant difference between the 2 treatment groups with respect to HCC size and clinical staging was observed, a higher proportion of patients with portal vein thrombosis (PVT) was treated with 131I-lipiodol than with TACE/TAE (28% vs. 8%, P = 0.003). Results: Actuarial survival was not significantly different between patients treated with 131I-lipiodol and patients treated with TACE/TAE. Survival at 6 mo, 1 y, 2 y, and 3 y was 86%, 69%, 54%, and 45%, respectively, after 131I-lipiodol, compared with 77%, 62%, 47%, and 43%, respectively, after TACE/TAE. However, patients with PVT survived a mean of 454 d after 131I-lipiodol, compared with a mean of 171 d after TACE/TAE (P = 0.025). In addition, patients with more advanced disease (Barcelona Clinic Liver Cancer stage D) lived on average 363 d after 131I-lipiodol, compared with 36 d after TACE/TAE (P = 0.014). Conclusion: In patients with unresectable HCC, there was no difference in survival between 131I-lipiodol therapy and TACE/TAE treatment. However, in the patients with advanced clinical staging or PVT, there was a significant survival advantage for those treated with 131I-lipiodol.