Franco Trevisani

Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?

BACKGROUND:The clinical usefulness of α-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable.OBJECTIVES:To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype.METHODS:A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor–nodes–metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity.RESULTS:Patients were divided into three AFP groups: normal (<20 ng/mL) [46%], elevated (21–400 ng/mL) [36%], and diagnostic (>400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (P = 0.0056), pain (P = 0.0025), Child-Pugh score (P = 0.001), tumor size, Okudas and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1–4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001).CONCLUSION:The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.

Effect of the Etiology of Viral Cirrhosis on the Survival of Patients with Hepatocellular Carcinoma

OBJECTIVES:The aim of this study was to assess whether hepatocellular carcinoma occurring in the setting of hepatitis B or C virus infection has different prognosis.METHODS:We performed a multicentric case-control study comparing 102 pairs of patients affected by hepatitis B virus- or hepatitis C virus-related hepatocellular carcinoma. Patients were matched for sex (male/female: 84/18 pairs), age, center, and period of enrollment, underlying chronic liver disease (cirrhosis/chronic hepatitis: 97/5 pairs), Child-Pugh class (A/B/C: 70/25/7 pairs), hepatocellular carcinoma stage (nonadvanced/advanced: 50/52 pairs) and, when possible, modality of cancer diagnosis (75 pairs: 47 during and 28 outside surveillance).RESULTS:In the whole population, patients with hepatitis B tended to have a poor prognosis than those with hepatitis C (P = 0.160), and this difference became statistically significant among the patients with an advanced hepatocellular carcinoma (P = 0.025). Etiology, Child-Pugh class, gross pathology, and alpha-fetoprotein were the significant independent prognostic factors in the whole population. The distribution of these prognostic factors did not differ between patients with hepatitis B or hepatitis C, both in the whole population and in the subgroup of advanced hepatocellular carcinomas.CONCLUSION:Hepatitis B virus-related hepatocellular carcinomas have a greater aggressiveness than hepatitis C virus-related tumors, which becomes clinically manifest once they have reached an advanced stage.

Surveillance for Early Diagnosis of Hepatocellular Carcinoma: Is It Effective in Intermediate/Advanced Cirrhosis?

OBJECTIVES:Surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on ultrasonography and alpha-fetoprotein (AFP) measurement, is widely used. Its effectiveness depends on liver function, which affects the feasibility of treatments and cirrhosis-related mortality. We assessed whether patients with intermediate/advanced cirrhosis benefit from surveillance.METHODS:We selected 468u2009Child-Pugh class B and 140u2009class C patients from the ITA.LI.CA database, including 1,834u2009HCC patients diagnosed from January 1987u2009to December 2004. HCC was detected in 252u2009patients during surveillance (semiannual 172, annual 80u2009patients; group 1) and in 356u2009patients outside surveillance (group 2). Survival of surveyed patients was corrected for the estimated lead time.RESULTS:Child-Pugh class B: cancer stage (P < 0.001) and treatment distribution (P < 0.001) were better in group 1u2009than in group 2. The median (95% CI) survivals were 17.1 (13.5–20.6) versus 12.0 (9.4–14.6) months and the survival rates at 1, 3, and 5 yr were 60.4% versus 49.2%, 26.1% versus 16.1%, and 10.7% versus 4.3%, respectively (P = 0.022). AFP, gross pathology, and treatment of HCC were independent prognostic factors. Child-Pugh class C: cancer stage (P = 0.001) and treatment distribution (P = 0.021) were better in group 1u2009than in group 2. Nonetheless, median survival did not differ: 7.1 (2.1–12.1) versus 6.0 (4.1–7.9) months (P = 0.740).CONCLUSIONS:These results suggest surveillance be offered to class B patients and maintained for class A patients who migrate to the subsequent class. Surveillance becomes pointless in class C patients probably because the poor liver function adversely affects the overall mortality and HCC treatments.

Liver Transplantation with the Meld System: A Prospective Study from a Single European Center

The efficacy of the Meld system to allocate livers has never been investigated in European centers. The outcome of 339 patients with chronic liver disease listed according to their Meld score between 2003 and 2005 (Meld era) was compared to 224 patients listed during the previous 2 years according to their Child score (Child era). During the Meld era, hepatocellular carcinomas (HCCs) had a ‘modified’ Meld based on their real Meld, waiting time and tumor stage. The dropouts were deaths, tumor progressions and too sick patients. The rate of removals from the list due to deaths and tumor progressions was significantly lower in the Meld than in the Child era: 10% and 1.2% versus 16.1% and 4.9%, p < 0.05. The 1‐year patient survival on the list was significantly higher in the Meld era (84% vs. 72%, p < 0.05). The prevalence of transplantation for HCC increased from 20.5% in the Child to 48.9% in the Meld era (p < 0.001), but between HCCs and non‐HCCs of this latter era the dropouts were comparable (9.4% vs. 14.9%, p = n.s.) as was the 1‐year patient survival on the list (83% vs. 84%, p = n.s.). The Meld allocation system improved the outcome of patients with or without HCC on the list.

Transcatheter Arterial Chemoembolization Therapy for Patients With Hepatocellular Carcinoma: A Case-Controlled Study

BACKGROUND & AIMSnTranscatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival.nnnMETHODSnFifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care.nnnRESULTSnThe 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis.nnnCONCLUSIONSnTACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.

Human herpesvirus -8 -related kaposi's sarcoma after liver transplantation successfully treated with cidofovir and liposomal daunorubicin

Abstract: The iatrogenic form of Kaposis sarcoma (KS) is typically observed among transplant recipients, and the most appropriate therapeutic approach (usually including reduction of immunosuppression, specific chemotherapy, and/or administration of antiviral agents against human herpes virus‐8) is still controversial. Available experiences on the effect of the anti‐herpes viruses drug cidofovir provide conflicting results. Herein, we report the clinical, histological, and virological features of a liver transplant recipient successfully treated with a combined therapy of cidofovir and liposomal daunorubicin, associated with a reduction of the immunosuppressive regimen, for an advanced cutaneous and visceral KS.