The Influence of Additional Treatments on the Survival of Patients Undergoing Transarterial Radioembolization (TARE).

The aim of this study was to present our preliminary experience with transarterial radioembolization (TARE) using Yttrium-90 (90Y), compare the cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) liver metastases undergoing TARE, and investigate the influence of additional treatments on CSS. Our database was interrogated to retrieve patients who had undergone TARE using Yttrium-90 (90Y) glass or resin microspheres. Kaplan-Meier curves and the log-rank test were employed to conduct survival analysis for the different groups (p < 0.05). Thirty-nine patients were retrieved (sex: 27 M, 12 F; mean age: 63.59 ± 15.66 years): twenty-three with hepatocellular carcinoma (HCC) and sixteen with CRC liver metastasis. Globally, the patients with HCC demonstrated a significantly longer CSS than those with CRC liver metastasis (22.64 ± 2.7 vs. 7.21 ± 1.65 months; p = 0.014). Among the patients with CRC liver metastasis, those receiving TARE and additional concomitant treatments (n = 10) demonstrated a longer CSS than the CRC patients receiving only TARE (9.97 ± 2.21 vs. 2.59 ± 0.24 months; p = 0.06). In the HCC group, there was a trend of a longer CSS in patients (n = 8) receiving TARE and additional treatments (27.89 ± 3.1 vs. 17.69 ± 3.14 months; p = 0.15). Patients with HCC seem to achieve a longer survival after TARE compared to patients with CRC liver metastases. In patients with CRC liver metastases, the combination of TARE and additional concomitant treatments may improve survival.

Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma.

Aims: To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods: A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results: Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions: Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC.

Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk for liver-related complications, such as decompensation, hepatocellular carcinoma (HCC), and death; the severity of liver fibrosis and metabolic comorbidities are the main risk factors. A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3 (PNPLA3) gene is associated with higher prevalence of liver damage and HCC, but there are no data from prospective studies of outcomes of patients with this polymorphism. We investigated whether the common rs738409 variant in PNPLA3 gene associates with the occurrence of liver-related events and death in a large cohort of patients with NAFLD. METHODS: We followed 471 consecutive individuals at a hospital in Italy with a diagnosis of NAFLD based on histologic factors or a diagnosis of compensated NAFLD-related cirrhosis based on clinical factors for at least 6 months, from March 2004 through December 2018. We collected data on the occurrence of hepatic and extrahepatic outcomes, including decompensation and HCC, cardiovascular events and extrahepatic cancers, and overall and liver-related death. We detected the rs738409 G>C polymorphism in DNA from patient blood samples using the TaqMan assay. RESULTS: During a median follow-up time of 64.6 months (range 6.1-175 months) 26 cases of decompensation, 13 HCCs, and 16 deaths (12 liver-related) were recorded. All liver-related events, including liver-related death, occurred in patients with F3 fibrosis or cirrhosis. The prevalence of PNPLA3 rs738409 GG, GT, and TT genotypes was 31.8%, 45.6%, and 22.6%, respectively. After adjusting for clinical, metabolic, and histologic risk factors, PNPLA3 C>G variant was associated with a higher risk of decompensation (hazard ratio [HR], 2.10; 95% CI, 1.03-4.29; P = .04), HCC (HR, 2.68; 95% CI, 1.01-7.26; P = .04), and liver-related death (HR, 3.64; 95% CI, 1.18-11.2; P = .02) by multivariate Cox regression analysis. In the subgroup of 162 patients with F3 fibrosis or cirrhosis, we confirmed the independent association between the PNPLA3 variant and decompensation (HR, 2.00; 95% CI, 1.01-3.97; P = .04), HCC (HR, 2.66; 95% CI, 1.02-7.13; P = .04), and liver-related death (HR, 3.64, 95% CI, 1.18-11.2; P = .02). We found no association between PNPLA3 genotype and cardiovascular events, extrahepatic cancers, or overall mortality. CONCLUSIONS: Patients with NAFLD carrying PNPLA3 rs738409 G>C variant are at higher risk of liver-related events and death.

PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12-7.71, p = 0.02, and OR4.11;95%C.I. 1.69-9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36-29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations.

Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.

BACKGROUND AND AIMS: Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis. METHODS: 843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT. RESULTS: By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120-6.564,p = 0.02), G1CHC (OR3.461,CI2.138-5.603,p<0.001) and CHB (OR2.778,CI1.042-7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079-15.970,p = 0.03 for NAFLD; OR2.250,CI1.211-4.181,p = 0.01 for G1CHC; OR3.096,CI2.050-34.220,p = 0.01 for CHB). CONCLUSIONS: In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.