Jean Claude Trinchet

Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis

Screening is widely used to detect early hepatocellular carcinoma in Asian patients with cirrhosis. Its effectiveness in Caucasian patients has been suggested, but remains to be proven. Therefore we prospectively studied 118 French patients (68 males, 50 females, age 55 +/- 12) with Child-Pugh A or B cirrhosis (alcoholic in 82) and without detectable hepatocellular carcinoma. The screening program consisted of ultrasound examination of the liver and determination of blood alpha-fetoprotein and des-gamma-carboxyprothrombin levels every 6 months. The median follow up was 36 months (range 4-48). Only four patients were lost to follow up. Fourteen hepatocellular carcinomas were detected, in six cases by ultrasonography alone, in four by alpha-fetoprotein alone, in three by ultrasonography and alpha-fetoprotein and in one case by ultrasonography and des-gamma-carboxyprothrombin, but never by des-gamma-carboxyprothrombin alone. The tumor presented as a unique nodule in nine patients. The tumor was less than 3 cm in diameter without portal thrombosis or metastasis in three cases. Surgery was performed in only one case. In this study, the annual incidence of hepatocellular carcinoma was high (5.8%), but the screening methods used did not effectively identify potentially resectable tumors in Caucasian patients with cirrhosis.

Radiofrequency ablation of hepatocellular carcinoma: Long‐term results and prognostic factors in 235 Western patients with cirrhosis

For the treatment of small hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) is in some centers considered a first‐line therapeutic option. However, such a strategy is still under debate with regard to tumor and patient characteristics. In this single‐center study we assessed the 5‐year survival and prognosis factors in 235 consecutive patients with cirrhosis (Child‐Pugh A/B: 205/30) who received RFA as first‐line treatment for up to three HCC ≤5 cm (307 tumors; mean diameter: 29 ± 10 mm; 53 multinodular forms). Among these patients, 67 satisfied the criteria for resection according to the Barcelona Clinic Liver Cancer. Complete ablation was obtained in 222 patients (94%). Overall, 337 RFA sessions were performed including iterative RFA for recurrence. Major complications occurred in three patients (0.9%), including one treatment‐related death. After 27 ± 20 months of mean follow‐up, local or distant, or both, tumor recurrence occurred in 16, 88, and 11 patients, respectively. Twenty‐nine patients underwent transplantation and were removed from the study at this point. Overall 5‐year, recurrence‐free, and tumor‐free (including results of iterative RFA) survival rates were, respectively, 40%, 17%, and 32%. The overall 5‐year survival rate was 76% for operable patients. Factors associated with overall survival were prothrombin activity (hazard ratio [HR] = 0.97, 0.96–0.98; P < 0.0001) and serum levels of α‐fetoprotein (AFP) (HR = 1.02, 1.02–1.02; P < 0.0001), and factors associated with tumor recurrence were multinodular forms (HR = 2.34; 1.52–3.6; P = 0.0001) and serum AFP levels (HR = 1.015, 1.014–1.016; P = 0.015). Tumor size was associated with local recurrence but not with overall and tumor‐free survival. Conclusion: RFA is a safe and effective first‐line treatment of HCC up to 5 cm in diameter, especially for patients with a single tumor, a low serum AFP level, and well‐preserved liver function. (HEPATOLOGY 2009.)

Large (≥5.0-cm) HCCs: Multipolar RF Ablation with Three Internally Cooled Bipolar Electrodes—Initial Experience in 26 Patients

PURPOSE To prospectively evaluate the safety and effectiveness of percutaneous multipolar radiofrequency (RF) ablation for the treatment of large (>or=5.0 cm in diameter) hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Twenty-six patients (four women, 22 men; median age, 72 years) with cirrhosis (Child-Pugh class A disease, 22 patients; Child-Pugh class B disease, four patients) and at least one 5.0-9.0-cm-diameter HCC without invasion of the portal trunk or main portal branches were treated with multipolar RF ablation performed by a single operator. The procedure was performed with three separate bipolar linear internally cooled electrodes with ultrasonographic guidance. Twenty-seven of the 33 tumors treated had a diameter of 5.0 cm or greater (median diameter, 5.7 cm; range, 5.0-8.5 cm); 12 of these 27 tumors were infiltrative, and four invaded segmental portal vein branches. Ten patients had a serum alpha-fetoprotein level higher than 400 microg/L. Results were assessed by using computed tomography. Primary effectiveness, complications, tumor progression, and survival rates were recorded. Probabilities of survival were calculated by using the Kaplan-Meier method. RESULTS One to two RF ablation procedures per patient (mean, 1.15 +/- 0.43 [standard deviation]) led to the complete ablation of 22 (81%) of the 27 tumors (18 tumors after one and four tumors after two procedures), including three tumors that showed segmental portal vein invasion. All patients experienced postablation syndrome, and one experienced subcapsular hematoma and a segmental liver infarct, but no major complication occurred. After a mean follow-up of 14 months (range, 3-34 months), local and distant tumor progression and actual survival rates were 14% (three of 22), 24% (five of 21), and 65% (17 of 26), respectively. The probabilities of 1- and 2-year survival, respectively, were 68% (95% confidence interval: 49%, 86%) and 56% (95% confidence interval: 51%, 81%). CONCLUSION HCCs larger than 5.0 cm (but smaller than 9.0 cm)--even those that are infiltrative and those that involve a segmental portal vein--can be completely and safely ablated with multipolar RF ablation.

Erythromycin Infusion or Gastric Lavage for Upper Gastrointestinal Bleeding: A Multicenter Randomized Controlled Trial

STUDY OBJECTIVE The quality of endoscopy depends on the quality of upper gastrointestinal tract preparation. We determine whether in acute upper gastrointestinal bleeding the frequency of satisfactory stomach visualization was different after intravenous erythromycin, a nasogastric tube with gastric lavage, or both. METHODS We performed a prospective, randomized, multicenter (6 emergency departments) study in patients with acute upper gastrointestinal bleeding presenting with hematemesis or melena. The patients were randomized into 3 groups: (1) intravenous erythromycin infusion without nasogastric tube placement (erythromycin group), (2) nasogastric tube placement without erythromycin (nasogastric group), and (3) intravenous erythromycin infusion combined with nasogastric tube placement (nasogastric-erythromycin group). The main outcome measure was the proportion of satisfactory stomach visualization. RESULTS Two hundred fifty-three patients (181 men, mean age 61 years [SD 15 years], 84 with cirrhosis) were randomized: 84 (erythromycin group), 85 (nasogastric group), and 84 (nasogastric-erythromycin group). Overall, there was 85% satisfactory stomach visualization; between-group differences were not significant: -4% (95% confidence interval [CI] -15% to 6%) for the erythromycin group and nasogastric-erythromycin group, 2% (95% CI -14% to 9%) for the erythromycin group and nasogastric group, and -6.5% (95% CI -17% to 4%) for the nasogastric group and nasogastric-erythromycin group. The duration of the endoscopic procedure, rebleeding frequency, the need for a second endoscopy, the number of transfused blood units, and mortality at days 2, 7, and 30 did not differ significantly between groups. CONCLUSION In acute upper gastrointestinal bleeding, administration of intravenous erythromycin provides satisfactory endoscopic conditions, without the need for a nasogastric tube and gastric lavage.

Survival after radiofrequency ablation and salvage transplantation in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis

BACKGROUND & AIMS In patients with hepatocellular carcinoma (HCC) within the Milan criteria, liver transplantation (LT) may be the best therapeutic option. However, the shortage of grafts, leads to attempt liver resection (LR) or radiofrequency ablation (RFA) as a first-line treatment for patients with Child-Pugh A cirrhosis. METHODS We report results, obtained between 2000 and 2007 from a single center, involving 67 patients (mean age: 57 years) eligible for LT, who were treated with RFA, followed by LT if there was recurrence or liver failure. RESULTS Eighty three tumors were treated (mean size: 29±9 mm; 16 binodular forms). RFA achieved complete ablation in 96% of nodules. No mortality occurred. During a post-RFA median follow-up of 48 months, 38 patients experienced recurrence, corresponding to a 5-year recurrence rate of 58%. Of these, 14 patients did not receive a transplant because they fell outside the Milan criteria, 21 were transplanted, and 3 were treated by RFA after refusing LT. Binodularity (95% CI HR=2, 1.0-4.0; p=0.049) was the unique risk factor for recurrence. By the studys end-point, 24 patients had undergone LT (21 for HCC recurrence and three for liver failure). No HCC recurrence occurred after LT. Among the 43 non-transplant patients, 12 died due to HCC progression, and 27 were alive without detectable viable tumor. The probability rates for 5-year overall and tumor-free survival were 74% and 69%, respectively. CONCLUSIONS First line RFA followed by salvage LT allows survival figures that are at least as good as a first-line LT, while limiting the number of grafts.

Intermediate Hepatobiliary Cells Predict an Increased Risk of Hepatocarcinogenesis in Patients With Hepatitis C Virus-Related Cirrhosis

BACKGROUND & AIMS The expression of biliary lineage markers such as cytokeratin (K) 7 by hepatocytes is thought to reflect an altered regeneration pathway recruiting a stem cell compartment, more prone to carcinogenesis. We aimed to investigate the presence of these so-called intermediate hepatobiliary cells (IHC) in liver biopsies of patients with hepatitis C-related cirrhosis and their potential influence on the subsequent occurrence of hepatocellular carcinoma (HCC). METHODS From a cohort of patients with hepatitis C-related cirrhosis, prospectively screened for HCC, we retrospectively selected those with a liver biopsy performed for the initial diagnosis of cirrhosis. Presence of IHC was recorded when foci of K7-positive, intermediate-sized hepatocytes were detected. RESULTS A total of 150 patients were included (87 men; mean age, 57 y; range, 19-84 y; body mass index, 25 kg/m(2)). After a median follow-up period of 4.85 years, HCC was diagnosed in 36 patients (24%). Baseline liver biopsy showed intermediate hepatobiliary cell foci in 61 patients (41%). Intermediate cells co-expressed both hepatocytes markers and the progenitor cell markers Ep-CAM and K19. The presence of intermediate hepatobiliary cells was associated independently with HCC occurrence (Fine and Gray model; hazard ratio, 2.48; 95% confidence interval, 1.24-4.96; P = .01). Other predictors of HCC were diabetes and low platelet count. The HCC annual incidence rate was significantly higher in patients with IHC compared with patients without (8.14% vs 3.12%, Grays test, P = .003). CONCLUSIONS The aberrant expression of biliary K by hepatocytes in patients with hepatitis C virus-related cirrhosis is related independently to HCC occurrence.

Ethanol versus radiofrequency ablation for the treatment of small hepatocellular carcinoma in patients with cirrhosis: A retrospective study of efficacy and cost

OBJECTIVE To compare cost effectiveness of radio-frequency (RF) ablation versus percutaneous ethanol (Pe) ablation for treatment of small hepatocellular carcinoma. METHODS 57 patients with 72 hepatocellular carcinomas (HCC) treated with ethanol ablation were retrospectively compared with 60 new patients who had 72 HCC treated with RF ablation. All patients had Child-Pugh A cirrhosis and HCC less than 3.5 cm in diameter. Therapeutic efficacy was evaluated with tri-phase spiral computed tomography. Cost of hospital stay, supplies and follow-up including complications were calculated. Survival was estimated by Kaplan-Meier method and prognostic value of treatment methods by Log Rank test and multivariate Cox proportional hazard model. RESULTS The two groups had similar baseline characteristics. The rate of severe complications associated with RF was 15% (9/60) vs 6,9% (9/60) with Pe (P=0,11) The two-year overall survival, disease free survival and local tumor free survival in the ethanol and radiofrequency groups were 70.8% vs. 91.2% (Odd Ratio=3.7, P=0.006), 48.6% vs. 71.1% (Odd Ratio=2.2, P=0.01), and 68.5% vs. 80.7%, (Odd Ratio=1.9; P=0.09), respectively. The treatment method was the sole significant factor related to overall and tumor free survival. Costs per patient of ethanol and radiofrequency treatments were 1534 euro and 1196 euro, respectively. CONCLUSION This retrospective study suggests that RF is the most cost effective strategy, with higher 2-year disease free survival rate.

Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV/HCV-co-infected patients: Results from ANRS CO13 HEPAVIH

BACKGROUND & AIMS Compared to HCV-mono-infected patients, hepatocellular carcinoma (HCC) occurs at younger age in HIV/HCV-co-infected patients, is markedly more advanced at diagnosis, is less amenable to curative treatment, and has a more severe outcome. The aim of this study was to identify factors predictive of HCC occurrence in a large cohort of HIV/HCV-co-infected patients with cirrhosis. METHODS This study involved 244 HIV/HCV-co-infected patients included in the ANRS CO13 HEPAVIH cohort, who had HCV-related cirrhosis (clinically or histologically proven cirrhosis, or liver stiffness ≥12.5 kPa) and no signs of HCC at baseline. Cox proportional hazards models were used to identify factors associated with HCC occurrence. RESULTS During a median follow-up of 2.6 (IQR, 1.8-3.5) years, 21 patients (8.6%) developed HCC. Diagnosis of HCC was based on histology in 5 patients (24%) and non-invasive criteria in 16 patients (76%). In univariate analyses, the following factors were related to HCC occurrence: age, previous cirrhosis decompensation, a HOMA value >3.8 (patients with treated diabetes were excluded from the HOMA calculation), a lower platelet count, a lower prothrombin level, and higher alpha-fetoprotein levels. The HOMA value was >3.8 at baseline in 66.7% of patients who developed HCC and in 35.3% of the remaining patients (p=0.016). In multivariate analysis, age over 50 years (adjusted RR 3.2, 95% CI 1.2-9.0; p=0.02) and a HOMA value >3.8 (adjusted RR 3.4, 95% CI 1.1-10.3; p=0.03) remained significantly associated with HCC occurrence. CONCLUSIONS As in HCV-mono-infected patients with HCV-related cirrhosis, insulin resistance appears to play a key role in HCC occurrence in HCV/HIV-co-infected patients with cirrhosis. This finding calls for specific screening strategies for patients with a particularly high risk of developing HCC.

Radiofrequency Ablation with Internally Cooled versus Perfused Electrodes for the Treatment of Small Hepatocellular Carcinoma in Patients with Cirrhosis

PURPOSE To compare the results of radiofrequency (RF) ablation with internally cooled electrodes (ICEs) versus perfused electrodes (PEs) in patients with cirrhosis with small (<or=3 cm) hepatocellular carcinoma ineligible for resection. MATERIALS AND METHODS Patients treated with RF ablation over two consecutive periods were analyzed retrospectively. From 2000 to 2002, 45 patients were treated with 17-gauge ICEs, and from 2002 to 2004, 44 patients were treated with 15-gauge PEs. The two groups were similar in age, sex, Child-Pugh stage, serum alpha-fetoprotein (AFP) level, and size and number of tumors (54 tumors in each group). Results were assessed by contrast medium-enhanced CT. RESULTS In both groups, 52 of 54 tumors (96.3%) were completely ablated. Eight of 54 tumors (14.8%) treated with ICEs and 39 of 54 tumors (72.2%) treated with PEs required multiple RF applications (P<.00005). In the respective groups, one of 54 tumors (1.8%) and seven of 54 tumors (12.9%) required multiple RF sessions (P=.03). Complication rates were similar. The 2-year probabilities of local and distant (ie, separated from the ablation zone) tumor progression in the ICE and PE groups were 11% and 15%, respectively (P=.65), and 31% and 64% (P=.01), respectively. On multivariate analysis, serum AFP level greater than 100 ng/mL (P=.006) and the use of a PE (P=.003) were risk factors for distant tumor progression. CONCLUSIONS RF ablation with the use of a PE requires more applications and sessions and is associated with a higher risk of distant tumor progression compared with the use of an ICE.