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Josep M Llovet

Publications and source records attributed to Josep M Llovet.

At least 19 recordsLinked to original sources
PubMed2023

International Liver Cancer Association (ILCA) white paper on hepatocellular carcinoma risk stratification and surveillance.

Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumours at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomised-controlled trial in patients with chronic HBV infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests. There are several proposed strategies to address these limitations, including risk stratification algorithms and biomarkers to better identity at-risk individuals, interventions to increase surveillance, and emerging imaging- and blood-based surveillance tests with improved sensitivity and specificity for early HCC detection. Beyond clinical validation, data are needed to establish clinical utility, i.e. increased early tumour detection and reduced HCC-related mortality. If successful, these data could facilitate a precision screening paradigm in which surveillance strategies are tailored to individual HCC risk to maximise overall surveillance value. However, practical and logistical considerations must be considered when designing and implementing these validation efforts. To address these issues, ILCA (the International Liver Cancer Association) adjourned a single topic workshop on HCC risk stratification and surveillance in June 2022. Herein, we present a white paper on these topics, including the status of the field, ongoing research efforts, and barriers to the translation of emerging strategies.

Humans↗
PubMed2004

Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation.

Preliminary reports suggested that hepatitis C virus (HCV) infection has a more aggressive course following living donor liver transplantation (LDLT) compared to cadaveric liver transplantation (CLT). The aim of this prospective study was to establish if HCV disease recurrence differs between LDLT and CLT. A cohort of 116 consecutive HCV-infected patients undergoing 117 LTs in a single center from March 2000 to August 2003 were followed-up, including systematic liver biopsies. Severe recurrence (SR) was defined as biopsy-proven cirrhosis and/or the occurrence of clinical decompensation. After a median follow-up of 22 months (2.6-44 months), 26 (22%) patients developed SR (decompensation in 12), involving 17 (18%) of 95 patients undergoing CLT and 9 (41%) of 22 undergoing LDLT. The 2-year probability of presenting SR was significantly higher in LDLT compared to CLT (45% vs. 22%, P = .019). By univariate analysis LDLT (P = .019) and an ALT higher than 80 IU/L 3 months after LT (P = .022) were predictors of SR. In 93 patients from whom a liver biopsy was available 3 months after LT, a lobular necroinflammatory score >1 (P < .01), LDLT (P < .01), and biliary complications (P = .046) were associated with SR. However, the only variables independently associated with SR were LDLT (odds ratio [OR], = 2.8; 95% CI,1.19-6.6; P = .024) and a lobular necroinflammatory score > 1 (OR, 3.1; 95% CI, 1.2-8; P = .013). In conclusion, HCV recurrence is more severe in LDLT compared to CLT. Although our results were based on a single-center experience, they should be considered in the decision-making process of transplant programs, since severe HCV recurrence may ultimately compromise graft and patient survival.

Adult↗
PubMed2004

Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.

Outcome predictors in patients with hepatocellular carcinoma (HCC) who are treated with percutaneous ablation are ill defined, and it is unknown if successful therapy is associated with improved survival. In our study, 282 cirrhotic patients with early nonsurgical HCC were treated with percutaneous ablation during a 15-year period. Single tumors were seen in 244 patients, and 2 to 3 nodules were seen in 38 patients. Initial complete response was achieved in 192 patients and was independently related to the size of the main tumor (P = .015) and tumor stage (P = .0001) (< or =2 cm, 96%; 2.1-3 cm, 78%; >3 cm, 56%; 2-3 nodules, 46%). At the end of follow-up, 80 patients presented sustained complete response. The 1-, 3-, and 5-year survival rates were 87%, 51%, and 27%, respectively. The independent predictors of survival were Child-Turcotte-Pugh class (P = .0001) and initial complete response (P = .006). Child-Turcotte-Pugh class A patients with initial complete response achieved 42% survival at 5 years; this figure increased to 63% in patients with tumors 2 cm or smaller. In conclusion, our results demonstrate that initial complete response to percutaneous ablation is associated with an improved survival in both Child-Turcotte-Pugh class A and B patients with nonsurgical HCC. Accordingly, initial complete tumor necrosis should be considered a relevant therapeutic target irrespective of tumor size and liver function.

Aged↗
PubMed2004

The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world, and the third most common cause of cancer-related death. It affects mainly patients with cirrhosis of any etiology. Patients with cirrhosis are thus usually included in surveillance plans aiming to achieve early detection and effective treatment. Only patients who would be treated if diagnosed with HCC should undergo surveillance, which is based on ultrasonography and alpha-fetoprotein every 6 months. Upon diagnosis, the patients have to be staged to define tumor extent and liver function impairment. Thereafter, the best treatment option can be indicated and a prognosis estimate can be established. The present manuscript depicts the Barcelona-Clínic Liver Cancer Group diagnostic and treatment strategy. This is based on the analysis of several cohort and randomized controlled studies that have allowed the continuous refinement of treatment indication and application. Surgical resection is considered the first treatment option for early stage patients. It is reserved for patients with solitary tumors without portal hypertension and normal bilirubin. If these conditions are not met, patients are considered for liver transplantation (cadaveric or live donation) or percutaneous ablation if at an early stage (solitary < or =5 cm or up to 3 nodules < or =3 cm). These patients will reach a 5-year survival between 50 and 75%. If patients are diagnosed at an intermediate stage and are still asymptomatic and have preserved liver function, they may benefit from chemoembolization. Their 3-year survival will exceed 50%. There is no effective treatment for patients with advanced disease and thus, in such instances, the patients have to be considered for research trials with new therapeutic options. Finally, patients with end-stage disease should receive only palliative treatment to avoid unnecessary suffering.

Administration, Cutaneous↗
PubMed2004

High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation.

Surgical resection and liver transplantation offer a 5-year survival greater than 70% in patients with hepatocellular carcinoma, but the high recurrence rate impairs long-term outcome after resection. Pathological data such as vascular invasion and detection of additional nodules predict recurrence and divide patients into high and low risk profile. Based on this, we proposed salvage liver transplant to resected patients in whom pathology evidenced high recurrence risk even in the absence of proven residual disease. From January 1995 to August 2003 we have evaluated 1,638 patients. Resection was indicated in 77 patients, but only 17 (22%) (all cirrhotics, 14 hepatitis C virus+) were optimal candidates for both resection and transplantation. Of them, 8 exhibited a high risk profile at pathology and were offered transplantation. Among the 8 high risk patients, 7 presented recurrence, compared with only 2 of the 9 at low risk (P = .012). Two of the high risk patients refused transplant and developed multifocal disease during follow-up. The other 6 were enlisted and all but 1 had tumor foci in the explant. Only 1 presented extrahepatic dissemination early after transplant and died 4 months later. The others are free of disease after a median follow-up of 45 months. Two recurrences were detected in low risk patients, 1 of them being transplanted 18 months after surgery. These data in a small series of patients confirm that pathological parameters identify patients at higher risk of recurrence, which allow them to be listed for liver transplantation without proven malignant disease. In conclusion, this policy is clinically effective and could further improve the outcome of resected patients.

Carcinoma, Hepatocellular↗
PubMed2004

Preoperative evaluation of biliary anatomy in adult live liver donors with volumetric mangafodipir trisodium enhanced magnetic resonance cholangiography.

Accurate preoperative depiction of biliary anatomy is not always adequately accomplished by imaging techniques in living donor liver transplantation (LDLT). We present the results of a prospective study designed to evaluate the ability of mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance (MR) cholangiography (MRC) for this purpose in a series of 25 adult living liver donors (LLDs). We also analyze if a simple or a more complex surgical procedure can be preoperatively suggested for biliary reconstruction in the recipients. Findings on MRC were compared with operative cholangiography (OC). A conventional distribution with a right hepatic duct (RHD) longer than 1 cm anticipated a simple procedure (duct-to-duct anastomosis or hepaticojejunostomy [HJ]). A shorter RHD or any variant were predictors of a more complex surgery (bench ductoplasty or multiple anastomoses). Agreement between MRC and OC in assessing the biliary anatomy was measured using the kappa statistic, and differences between the kind of surgery predicted at MRC and the biliary anastomosis performed were evaluated with Fisher's exact test. Normal variants were present in 16 / 25 donors (64%). MRC was accurate in depicting the pattern of bile duct distribution observed at OC in 22 / 25 (88%) donors (kappa = .831), and correctly predicted the complexity of biliary anastomosis in the recipient in 22 / 25 (88%) donors. No significant differences were observed between complexity of biliary surgery proposed at MRC and the final surgery performed (P = .002). In conclusion, Mn-DPDP-enhanced MRC is highly accurate in depicting the biliary duct anatomy and can be used preoperatively for surgical planning in LDLT.

Adult↗
PubMed2004

Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma is the fifth leading cause of cancer worldwide and its incidence is increasing. Surveillance programs allow doctors to identify patients at early stages of the disease, when the tumor may be curable by radical treatments such as resection, liver transplantation, or local ablation. In the West, these treatments can be applied to 30% to 40% of patients. Resection yields favorable results in patients with single tumors and a well-preserved liver function (5-year survival rate is 60%). Recurrence complicates two thirds of the cases, and there is no effective adjuvant treatment. Liver transplantation is the best treatment for patients with single tumors that are less than 5 cm in diameter and liver failure, or in those presenting with three nodules less than 3 cm, but organ shortage greatly limits its applicability. Long-term survival is expected to be around 50% to 70% at 5 years depending upon the drop-out rate of patients on the waiting list. Chemoembolization and local ablation are the neo-adjuvant treatments applied to patients on the waiting list to prevent tumor progression; no controlled study proving their efficacy has yet been published. In nonsurgical candidates, percutaneous treatments (ethanol injection or radiofrequency ablation) are the best therapeutic approach and improve survival in Child-Pugh A class patients with small tumors that achieve initial complete response (5-year survival rate is 40% to 50%). At more advanced stages, chemoembolization, a technique combining intra-arterial chemotherapy and selected ischemia, has shown to slightly improve survival in a meta-analysis of randomized trials. No survival advantages have been demonstrated with intra-arterial or systemic chemotherapy, hormonal compounds, or radiation. New agents, such as inhibitors of the tyrosine kinase receptors of growth factors and antiangiogenic agents, are currently being tested in phase II/III trials.

Journal Article↗
PubMed2004

Chemoembolization for hepatocellular carcinoma.

Curative therapies for hepatocellular carcinoma (HCC), such as resection, liver transplantation, and percutaneous ablation, can be applied in selected patients with early tumors; this includes approximately 30%-40% of all cases. More advanced stages require local or systemic therapies. Data on the efficacy of these treatments are derived from small randomized controlled trials (RCT) and meta-analysis. Chemoembolization, a technique combining intra-arterial chemotherapy and selected ischemia, has produced modest survival advantages in 2 RCTs and a meta-analysis, and is currently the mainstay of treatment for these stages. The ideal candidates for this option are patients with well-preserved liver function (Child-Pugh class A) and multinodular asymptomatic tumors without vascular invasion, who constitute less than 15% of the HCC population. In these cases, the benefits derived by achieving objective responses (30%-50% of cases) are not offset by the deterioration of the liver function. Treatment-related mortality is less than 4%. No survival advantages have yet been shown with embolization or intra-arterial chemotherapy alone. Further RCTs are needed to assess the best chemotherapeutic agent and the ideal retreatment schedule. The analysis of efficacy in these trials should be adjusted for prognostic factors, such as the presence of symptoms, Child-Pugh class, and segmental vascular invasion.

Carcinoma, Hepatocellular↗
PubMed2003

Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, and its incidence is increasing worldwide because of the dissemination of hepatitis B and C virus infection. Patients with cirrhosis are at the highest risk and should be monitored every 6 months. Surveillance can lead to diagnosis at early stages, when the tumour might be curable by resection, liver transplantation, or percutaneous treatment. In the West and Japan, these treatments can be applied to 30% of patients, and result in 5-year survival rates higher than 50%. Resection is indicated among patients who have one tumour and well-preserved liver function. Liver transplantation benefits patients who have decompensated cirrhosis and one tumour smaller than 5 cm or three nodules smaller than 3 cm, but donor shortage greatly limits its applicability. This difficulty might be overcome by living donation. Most HCC patients are diagnosed at advanced stages and receive palliative treatments, which have been assessed in the setting of 63 randomised controlled trials during the past 25 years. Meta-analysis shows that only chemoembolisation improves survival in well-selected patients with unresectable HCC.

Carcinoma, Hepatocellular↗
PubMed2003

p27(Kip1) is an independent predictor of recurrence after surgical resection in patients with small hepatocellular carcinoma.

BACKGROUND/AIMS: Alterations in p27(Kip1) (p27) and cyclin E (cycE) expression are found in tumors and are related to poor prognosis. This study assesses the role of these cell cycle regulators in the development of recurrence after surgical resection in 46 cirrhotic patients (age: 61.3+/-7 years, 30 males, 44 Child-Pugh's A, 30 HCV-positive) with small hepatocellular carcinoma (HCC, size: 3.1+/-1.5cm, 40 solitary at pathological examination). METHODS: p27 and cycE expression in tumoral and non-tumoral liver were analyzed by Western blot (WB). p27 was also assessed by immunohistochemistry (IHC). RESULTS: Tumor p27 underexpression (50% decreased vs. non-tumoral liver) occurred in 12 cases. Throughout follow-up, 26 patients developed recurrence, which was significantly higher in patients with p27 underexpression than in those without (3-year recurrence: 80 vs. 44%, respectively, P=0.026). IHC showed concordant inverse findings: 13 tumors showed high p27 staining that was related to lower recurrence rate (P=0.019). Multivariate analysis identified p27 measured by WB as an improved predictor of recurrence (OR: 3.09, 95% CI: 1.26-7.08, P=0.016). By contrast, cycE, increased in 66% of the tumors, had no impact on recurrence but was associated to poor differentiation (P=0.015) and microvascular invasion (P=0.016). CONCLUSIONS: p27 underexpression is frequent in relatively early stages of HCC and constitutes an independent predictor of recurrence after surgical resection.

Aged↗
PubMed2003

Treatment of hepatocellular carcinoma: is there an optimal strategy?

The incidence of hepatocellular carcinoma is increasing worldwide and now it accounts for as many as 1 million deaths annually, representing the third cause of cancer-related death. Surveillance programmes in the population at risk, namely cirrhotic patients, aim to detect tumours at an early stage when benefit from effective therapy may be provided. Patients with early tumours (single tumours measuring less than 5 cm or with less than 3 nodules measuring less than 3 cm in size) constitute the early stage category. These patients may be treated with surgical resection, transplantation, or percutaneous ablation, and the 5-year survival rate will exceed 50%. Patients with more advanced disease constitute the intermediate-advanced stage. Intermediate stage includes individuals without cancer-related symptoms and absence of vascular invasion and/or extrahepatic spread. They may achieve a 50% survival rate at 3 years that can be expanded by transarterial chemoembolization. Symptomatic patients with more advanced disease have a survival rate of less than 20% at 3 years. In this group of patients the efficacy of new agents should be assessed in phase II trials or randomized controlled trials versus no treatment to determine the impact of any therapy on survival. Finally, patients with end-stage disease with heavily impaired liver function (Child-Pugh class C) or severe physical impairment (performance status 3-4) die within 6 months and should receive only symptomatic treatment.

Carcinoma, Hepatocellular↗
PubMed2003

Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival.

There is no standard treatment for patients with unresectable hepatocellular carcinoma (HCC). Survival benefits derived from medical interventions are controversial. The aim of this systematic review was to assess the evidence of the impact of medical treatments on survival. Randomized controlled trials (RCTs) that were published as full papers assessing survival for primary treatments of HCC were included. MEDLINE, the Cochrane Library, CANCERLIT, and a manual search from 1978 to May 2002 were used. The primary end point was survival, and the secondary end point was response to treatment. Estimates of effect were calculated according to the random effects model. Sensitivity analysis included methodological quality. We identified 61 randomized trials, but only 14 met the criteria to perform a meta-analysis assessing arterial embolization (7 trials, 545 patients) or tamoxifen (7 trials, 898 patients). Arterial embolization improved 2-year survival compared with control (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.89; P =.017). Sensitivity analysis showed a significant benefit of chemoembolization with cisplatin or doxorubicin (OR, 0.42; 95% CI, 0.20-0.88) but none with embolization alone (OR, 0.59; 95% CI, 0.29-1.20). Overall, treatment induced objective responses in 35% of patients (range, 16%-61%). Tamoxifen showed no antitumoral effect and no survival benefits (OR, 0.64; 95% CI, 0.36-1.13; P =.13), and only low-quality scale trials suggested 1-year improvement in survival. In conclusion, chemoembolization improves survival of patients with unresectable HCC and may become the standard treatment. Treatment with tamoxifen does not modify the survival of patients with advanced disease.

Carcinoma, Hepatocellular↗