Pietro Parisi

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems

Background  A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately.

Combined treatment of relapse of chronic hepatitis C with high-dose α2b interferon plus ribavirin for 6 or 12 months

BACKGROUND/AIMS Retreatment of relapses of chronic hepatitis C with a standard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b. We aimed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness, and also to evaluate the tolerability, and to identify the determinants of sustained response. METHODS Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of a-interferon monotherapy were randomised to receive alpha2b interferon (6 MU tiw) plus ribavirin (1000-1200 mg daily) for 6 or 12 months. ALT normalisation and serum HCV-RNA clearance at the end of treatment and 6 months after stopping therapy were used as markers for sustained response. RESULTS End-of-treatment response was achieved in 48 patients (96%) and 27 (54%) had a complete sustained response. Patients treated for 12 months had a higher rate of sustained response (18/25, 72%; 95% C.I. 0.54-0.89) than those treated for 6 months (9/25, 36%; 95% C.I. 0.17-0.55, p=0.01). Twelve months of therapy was significantly more effective for patients with genotype 1b and baseline serum HCV-RNA greater than 450 000 copies/ml (p=0.005). Seven subjects (14%) discontinued treatment because of side effects. Logistic regression analysis showed 12 months of therapy, young age and low pre-treatment serum HCV-RNA to be independent predictors of sustained response. CONCLUSIONS Relapsers with genotype 1b and high levels of HCV-RNA will benefit from a 12-month course of 6 MU tiw interferon plus ribavirin, while subjects with genotype 1b and low levels of serum HCV-RNA or with genotype other than 1b may be treated for 6 months.

Natural history of untreatable hepatocellular carcinoma: A retrospective cohort study

AIM To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality. METHODS From January 1999 to December 2010, 320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected for each patient including all clinical, laboratory and imaging variables necessary for the outcome prediction staging systems considered. HCC staging was performed according Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program scores. Follow-up time was defined as the number of months from the diagnosis of HCC to death. Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival. RESULTS Seventy-five per cent of patients had hepatitis C. Ascites was present in 169 patients (53%), while hepatic encephalopathy was present in 49 patients (15%). The Child-Pugh score was class A in 105 patients (33%), class B in 142 patients (44%), and class C in 73 patients (23%). One hundred patients (31%) had macroscopic vascular invasion and/or extra-hepatic spread of the tumor. A single lesion > 10 cm was observed in 34 patients (11%), while multinodular HCC was present in 189 patients (59%). Thirty nine patients (12%) were BCLC early (A) stage, 55 (17%) were BCLC intermediate (B) stage, 124 (39%) were BCLC advanced (C) stage, and 102 (32%) were end-stage BCLC (D). At the time of this analysis (July 2011), 28 (9%) patients were still alive. Six (2%) patients who were lost during follow-up were censored at the last visit. The overall median survival was 6.8 mo, and the 1-year survival was 32%. The 1-year survival according to BCLC classes was 100%, 79%, 12% and 0%, for BCLC A, B, C and D, respectively. There was a significant difference in survival between each BCLC class. The median survival of patients of BCLC stages A, B, C and D was 33, 17.4, 6.9, and 1.8 mo, respectively (P < 0.05 for comparison between stages). The median survival of Child-Pugh A, B and C classes were 9.8 mo (range 6.4-13), 6.1 (range 4.9-7.3), and 3.7 (range 1.5-6), respectively (P < 0.05 for comparison between stages). By univariate analysis, the variables significantly associated to an increased liklihood of mortality were Eastern Cooperative Oncology Group performance status (PS), presence of ascites, low level of albumin, elevated level of bilirubin, international normalized ratio (INR) and Log-[(α fetoprotein (AFP)]. At multivariate analysis, mortality was independently predicted by bad PS (P < 0.0001), high INR values (P = 0.0001) and elevated Log-(AFP) levels (P = 0.009). CONCLUSION This study confirms the heterogeneous behavior of untreated HCC. BCLC staging remains an important prognostic guide and may be important in decision-making for palliative treatment.

Seeding after radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis: A prospective study

BACKGROUND Neoplastic seeding of hepatocellular carcinoma may arise after radiofrequency ablation. AIMS In order to clarify the real risk of seeding, we observed a prospective cohort of patients undergoing radiofrequency ablation. METHODS Ninety-three (22.9%) out of 406 consecutive patients with hepatocellular carcinoma superimposed to cirrhosis diagnosed at our Liver Unit (2000-2005) were selected for radiofrequency ablation according to the Barcelona 2000 EASL guidelines. Seventy-one patients were treated by a percutaneous approach and 22 at laparotomy. After radiofrequency ablation ultrasound scan was repeated every 3 months and spiral-computed tomography every 6 months. RESULTS Overall 145 sessions were performed in 93 patients: 113 (77.9%) by a percutaneous approach and 32 (22.1%) at laparotomy. The median follow-up was 23 months (range 1-60). Only 1 of the 71 patients (1.4%; 95% C.I. 0.25-7.56) treated percutaneously and none of the 22 (0%; 95% C.I. 0-14.8) treated at laparotomy showed neoplastic seeding. CONCLUSION In our experience the risk of seeding of hepatocellular carcinoma after radiofrequency ablation was small (1.1% per patient, 95% C.I. 0.19-5.84; 0.7% per procedure, 95% C.I. 0.12-3.80). A stringent selection of patients for radiofrequency ablation and retraction of the needle with a hot tip may have been instrumental in obtaining this low frequency.