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Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Chronic HCV infection is also an important cause of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV has the capacity to evade immune surveillance by altering the host immune response. Moreover, variations in immune-related genes can lead to differential susceptibility to HCV infection as well as interfere on the susceptibility to the development of hepatic fibrosis, cirrhosis and HCC. The human leucocyte antigen G (HLA-G) gene codes for an immunomodulatory protein known to be expressed in the maternal-foetal interface and in immune-privileged tissues. The HLA-G 3' untranslated region (3'UTR) is important for mRNA stability, and variants in this region are known to impact gene expression. Studies, mainly focusing in a 14 bp insertion/deletion polymorphism, have correlated HLA-G 3'UTR with susceptibility to viral infections, but other polymorphic variants in the HLA-G 3'UTR might also affect HCV infection as they are inherited as haplotypes. The present study evaluated HLA-G 3'UTR polymorphisms and performed linkage disequilibrium test and haplotype assembly in 286 HCV infected patients who have developed fibrosis, cirrhosis or HCC, as well as in 129 healthy control subjects. Haplotypes UTR-1, UTR-2 and UTR-3 were the most observed in HCV+ patients, in the frequencies of 0.276, 0.255 and 0.121, respectively. No statistically significant difference was observed between HCV+ and control subjects, even when patients were grouped according to outcome (HCC, cirrhosis or fibrosis). Despite that, some trends in the results were observed, and therefore, we cannot rule out the possibility that variants associated to high HLA-G expression can be involved in HCV infection susceptibility., (© 2023 John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV-induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06-3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00-3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.

Background: Current policy for listing to liver transplant (LT) may place cirrhotic patients without MELD exception points (CIR) in a disadvantageous position if compared to patients enlisted with appealed MELD scores - patients with hepatocellular carcinoma (HCC) or special conditions other than hepatocellular carcinoma (SPE). Transplant rates, delisting, and waitlist mortality of CIR, HCC, and SPE candidates were compared., Objective: The aim of this study is to counterweight the listing rate and speed of listing of HCC, SPE, and CIR patients. To the best of our knowledge, this is the first study comparing the outcomes of patients enlisted for SPE to those of HCC and CIR. In several countries worldwide, SPE patients also receive appealed MELD scores in a similar way of HCC patients., Methods: Two cohorts of patients listed for LT in a single institution were evaluated. The first cohort (C1, n=180) included all patients enlisted on August 1st, 2008, and all additional patients listed from this date until July 31st, 2009. The second cohort (C2, n=109) included all patients present on the LT list on October 1st, 2012, and all additional patients listed from this date until May 2014., Results: In both cohorts, HCC patients had a higher chance of receiving a LT than CIR patients (C1HR =2.05, 95%CI=1.54-2.72, P<0.0001; C2HR =3.17, 95%CI =1.83-5.52, P<0.0001). For C1, 1-year waiting list mortality was 21.6% (30.0% for CIR vs 9.5% for HCC vs 7.1% for SPE) (P<0.001). For C2, 1-year waiting list mortality was 13.3% (25.7% for CIR, 8.3% for HCC, and 4.0% for SPE) (P<0.001). Post-transplant survival was similar among the three groups., Conclusion: Compared to CIR, SPE and HCC patients had lower wait list mortality. CIR patients had the highest waitlist mortality and the lowest odd of LT. Current LT allocation system does not allow equitable organ allocation.

Introduction: The intermediate stage of the Barcelona Clinic Liver Cancer (BCLC) classification includes a heterogenous population of patients with hepatocellular carcinoma (HCC), and palliative treatment with transarterial chemoembolization is recommended for all of them. In this regard, 2 other classifications could be useful, the subclassification BCLC-B (SUB) and the classification Hong Kong Liver Cancer (HKLC)., Objective: To determine the indication of curative or palliative treatment between SUB and HKLC in BCLC-B patients., Patients and Methods: A retrospective study in HCC patients seen between 2011 and 2016 in southern Brazil. Demographic, clinical, and laboratory data were collected. HCC staging was performed with BCLC, SUB, and HKLC., Results: A total of 570 patients with HCC were assessed, of whom 95 were classified as BCLC-B: 25 (26.0%) B1, 48 (50.5%) B2, 9 (9.5%) B3, and 13 (13.7%) B4. Overall median survival was 21.1 (95% confidence interval, 14.2-28.0) months. Median survival was higher for BCLC-B1 patients than in subgroups B3 (P=0.046) and B4 (P=0.001), and this was also seen for B2 versus B4 (P=0.044). Regarding the HKLC classification, a significantly higher median survival was observed for HKLC-I and HKLC-IIB in relation to the categories HKLC-IIIA (P<0.001 and 0.004, respectively) and HKLC-IIIB (P<0.001 and 0.006, respectively). When HKLC was applied, the following were identified as candidates for curative treatment: BCLC-B1, 24 (96.0%); BCLC-B2, 26 (54.2%); BCLC-B3, 0 (0%); and BCLC-B4, 3 (23.1%)., Conclusion: In intermediate HCC, SUB was able to identify a subset of patients with a higher overall survival. According to HKLC, 55.8% of BCLC-B patients could receive curative treatment.

Introduction: Sorafenib (SOR) has proved to be effective in patients with advanced hepatocellular carcinoma (HCC), since overall survival was higher in phase III clinical trials; however, disease progression can occur., Objectives: The study aimed to describe real-life experience in advanced HCC treatment with SOR at a university hospital in Brazil and to estimate the number of patients with indication of second-line therapy., Methods: This is a retrospective study that included cases of HCC with prescription of SOR based on real-life practice between 2011 and 2016. Demographic, clinical, and laboratory data were collected., Results: From 572 patients with HCC, SOR was prescribed in 103 cases. From them, 62.1% were classified as Child-Pugh (CP)-A, 54.4% as Barcelona Clinic Liver Cancer (BCLC)-C, and 74 (71.8%) started treatment. Overall survival was 25.5 (95% CI 17.0-34.1) months and 1-year survival was greater in patients who received SOR than in non-treated (88.7 vs. 44.4%, p < 0.001). There was no difference in survival between BCLC-B and C (p = 0.405), as well as CP-A and B (p = 0.919). In 21.6% of the patients, a second-line therapy with regorafenib was indicated., Conclusion: In this real-life study, SOR significantly increased the survival rate by 1 year in patients with advanced HCC regardless of BCLC staging and CP score. Second-line therapy would be indicated in 21.6% of cases., (© 2018 S. Karger AG, Basel.)