Epidemiology of Liver Cancer in Latin America: Current and Future Trends.

Over 38,000 cases of hepatocellular carcinoma (HCC) are estimated to occur in Latin America annually. The region is characterized by sociocultural heterogeneity and economic disparities, which impose barriers in addressing this major health issue. A significant proportion of patients are still diagnosed in the later stages of the disease, although efforts to implement effective screening programs have been reported by referral centers. While viral hepatitis remains the predominant etiology of liver disease among HCC cases in Latin America, a high prevalence of fatty liver disease in the region is a matter of concern, reflecting the current scenario in many Western countries. In addition, other risk factors such as alcohol, aflatoxin, and early-onset HCC in hepatitis B virus infection contribute to the burden of HCC in Latin America. Interventions to increase screening coverage, expand healthcare access, and implement continuing medical training are key challenges to be overcome.

Multimodality Screening of Hepatic Nodules in Patients With Congenital Heart Disease After Fontan Procedure: Role of Ultrasound, ARFI Elastography, CT, and MRI.

OBJECTIVE: Currently, there is no consensus in the literature regarding the screening of hepatic nodules in patients who have undergone the Fontan procedure. The objectives of this study are to evaluate in this population the frequency of hepatic nodules at ultrasound (US), CT, and MRI; to measure liver stiffness using acoustic radiation force impulse (ARFI) elastography; and to investigate predictive factors for hepatic nodules. SUBJECTS AND METHODS: In this cross-sectional study, 49 patients who underwent the Fontan procedure were prospectively recruited from August 2014 through June 2016. These patients underwent clinical evaluation for hepatic disorders, ARFI elastography, US, CT, and MRI. RESULTS: Most of the patients had no symptoms, and hepatic nodules were detected in three of 49 (6.1%) patients at US, 14 of 44 (31.8%) patients at CT, and 19 of 48 (39.6%) patients at MRI. Liver stiffness at ARFI elastography was significantly higher in patients with hepatic nodules than in patients without such nodules (2.64 ± 0.81 m/s vs 1.94 ± 0.49 m/s; p = 0.002) and was a significant predictor of hepatic nodule (AUC, 0.767; p = 0.002). No clinical or laboratory data had any significant correlation with the existence of hepatic nodules, including time since Fontan procedure. CONCLUSION: In our study, more than one-third of patients had hepatic nodules at CT or MRI, but US did not detect most hepatic nodules. Liver stiffness at ARFI elastography was significantly higher in patients with hepatic nodules, and it may help guiding which patient should be further imaged with CT or MRI.

Significance of CT scan and color Doppler duplex ultrasound in the assessment of Abernethy malformation.

BACKGROUND: Abernethy malformation is a rare congenital vascular abnormality in which the portal vein bypasses the liver and drains directly into the inferior vena cava. Diagnosis is complex and requires good quality imaging methods to identify details in systemic and portal circulation in order to establish diagnostic confirmation and treatment strategy. In this study we highlight the significance of the use of CT scans and Color Doppler Duplex Ultrasound for the diagnosis, treatment and evolution assessment in two adults with Abernethy malformation. CASE PRESENTATION: The diagnosis and the treatment of two patients with Abernethy malformation by CT scan and Color Doppler Duplex Ultrasound is described. One patient was submitted to liver transplantation due to chronic liver disease and multiple nodules diagnosed as adenoma. The other patient had normal liver function and a mild neurological and psychomotor dysfunction, therefore we adopted clinical treatment and close liver parenchyma evaluation and nodule surveillance, using an imaging approach involving intercalating CT scan and Color Doppler Duplex Ultrasound every 6 months. We highlight some important direct and indirect findings of non-invasive imaging methods. CONCLUSION: Abernethy malformation requires meticulous image diagnosis to improve treatment and avoid iatrogenic procedures. CT scans and Color Doppler Duplex Ultrasound are both efficient methods for diagnosis, treatment planning and evolution assessment of patients with Abernethy malformation.

m-RECIST at 1 month and Child A are survival predictors after percutaneous ethanol injection of hepatocellular carcinoma.

BACKGROUND AND AIMS: Percutaneous ethanol injection (PEI) is a well-established therapeutic option in patients with cirrhosis and hepatocellular carcinoma (HCC). The modified-Response Evaluation Criteria in Solid Tumors (m-RECIST) are an important tool for the assessment of HCC response to therapy. The aim was to evaluate whether HCC response according to the m-RECIST criteria could be an effective predictor of long-term survival in Barcelona Clinic Liver Cancer (BCLC) stage 0 and A HCC patients undergoing PEI. MATERIAL AND METHODS: 79 patients were followed-up for median time of 26.8 months. HCC diagnosis was based on the current guidelines of the American Association for Study of the Liver Diseases (AASLD) and European Association for Study of the Liver (EASL). Patient survival was calculated from the first PEI session to the end of the follow-up. RESULTS: The 1-, 3-, and 5-year overall survival rates were 79, 48 and 37%, respectively. In the multivariate analysis, Child-Pugh-Turcotte (CPT) (p = 0.022) and the response to m-RECIST criteria (p = 0.016) were associated with patient survival. CPT A patients who achieved Complete Response (CR) 1 month after PEI presented a 5-year survival rate of 55%. By contrast, the worst scenario, the group with CPT B but without CR had a 5-year survival rate of 9%, while the group with either CPT A or CR as a survival predictor had a 5-year survival rate of 31%. In conclusion, in BCLC stage 0 and A HCC-patients, m-RECIST at 1 month and Child A may predict survival rates after PEI.

Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort.

BACKGROUND AND AIM: The lack of information about hepatocellular carcinoma (HCC) in Brazil weakens health policy in preventing deaths from the illness. The aim of this study was to establish the cumulative incidence and the risk factors for hepatocellular carcinoma development in patients under a surveillance program. MATERIAL AND METHODS: 884 patients with compensated cirrhosis were prospectively followed up for at least five years, from August 1998 until August 2008, with at least one annual ultrasonography liver examination and serum alpha fetoprotein (AFP) measurement. RESULTS: Among 884 patients, 72 (8.1%) developed a tumor with a median follow up of 21.4 months. In the hepatocellular carcinoma group, hepatitis C virus infection was the major etiological factor (65.3%), 56.9% (41/72) were male and the mean average age was 57 ± 10 years. The annual incidence of hepatocellular carcinoma was 2.9%. 79.2% (57/72) of HCCs were detected within Milan Criteria, and the mean survival time was 52.3 months, significantly higher than for those outside Milan, with a mean time of 40.6 months (p = 0.0003). CONCLUSION: The annual incidence of HCC among this large series of Brazilian cirrhotic patients was around 2.9% with a detection rate of 8.1%, or a cumulative incidence rate over five years of 14.3%. The three variables related to HCC risk were low serum albumin [HR: 0.518 (0.46-0.78)], high AFP > 20 ng/mL [HR: 3.16 (1.86-5.38)], and ethnicity (Brazilian-East Asian descendants vs. other mixed Brazilian ethnicities) [HR: 2.86 (1.48-5.53)].

Liver elastography can predict degree of advanced fibrosis for autoimmune hepatitis in biochemical remission.

Background and Aim: The aim was to analyze the concordance of liver stiffness measurement (LSM) either by transient elastography (TE) or ARFI with liver biopsy in autoimmune hepatitis (AIH) patients with biochemical remission and to identify those with histological remission. Liver biopsy is still the golden standard for AIH diagnosis. However, it is an invasive procedure and these patients, most of the time, require many biopsies, so it would be valuable to search for noninvasive method that could select all these patients and keep under observation. Methods: Thirty-three patients with AIH were submitted for liver biopsy to evaluate histological remission after at least 18 months of normal aminotransferases. The efficiency of LSM and fibrosis stages was tested by a receiver operating characteristic curve analysis (AUROC). Results: One patient (3%) was F0, 6 (18.2%) were F1, 8 (24.2%) were F2, 10 (30.3%) were F3, and 8 (24.2%) were F4, according to METAVIR. Thirteen of thirty-three (39.4%) patients did not achieve histological remission. AUROC for F4 stage was 0.83 (IC: 0.76-0.99) for TE and 0.78 (IC: 0.65-0.95) for ARFI. Optimal LSM cutoff values were 12.3 kPa (Se = 87.5%, Sp = 88%) for TE and 1.65 m/s (Se = 87.5%, Sp = 76%) for ARFI. The tests were unable to differentiate patients with histological activity from those in histological remission (P < 0.05). Conclusion: TE and ARFI accurately identify liver fibrosis by METAVIR score in AIH patients with biochemical remission. No cutoff value was detected to indicate whether the patient achieved histological remission.

HIGH VALUES OF LIVER STIFFNESS PLAY AN IMPORTANT ROLE IN STRATIFYING THE RISK OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC HEPATITIS C PATIENTS.

BACKGROUND: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. METHODS: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. RESULTS: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). CONCLUSION: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.

Liver Elastography in Acute Cellular Rejection After Liver Transplantation.

BACKGROUND: Transient elastography is a noninvasive method used to estimate the liver stiffness. There are few studies using elastography in acute cellular rejection (ACR). ACR is one of the main complications after liver transplantation. The golden pattern diagnostic is by liver biopsy, which is invasive and subject to complications. Therefore, this paper aims to evaluate the use of elastography in ACR. METHODS: Prospective and comparative study of patients transplanted from January 2017 to March 2019. Comparison group (ACR vs non-ACR) through liver biopsy. The variables analyzed were liver elastography (FibroScan and acoustic radiation force impulse [ARFI]), laboratory tests, liver biopsy, and ultrasound. Mann-Whitney U test was used to compare independent samples, and P < .05 was considered significant. All tests performed with α of 0.05 and a confidence interval of 95%, by IBM SPSS 25 software. RESULTS: Forty patients, 25 (62.5%) with ACR and 15 (37.5%) without ACR. Five (20%) cases with early acute rejection, late acute rejection in 19 cases (76%), and chronic rejection in 3 (12%). Comparative ACR vs non-ACR showed results of total bilirubin (P = .03), direct bilirubin (P = .015), aspartate aminotransferase (0.001), alanine aminotransaminase (0.001), and gamma-glutamyl transferase (P = .026). The mean elastography (FibroScan) value in ACR was 12.5 ± 8.2 kPa and without was 8.9 ± 3.7 kPa, P = .05. The mean elastography (ARFI) in ACR was 1.9 ± 0.6 m/s and without was 1.6 ± 0.2 m/s, P > .05. The receiver operator characteristic curve analysis shows the FibroScan for ACR with AUC 0.688 (95% CI 0.511-0.865), P = .049, positive predictive value 0.76, and negative predictive value 0.60. CONCLUSIONS: Transient elastography is an important tool for ACR. There is a significant correlation between ACR and the value of hepatic elastography.

249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients.

BACKGROUND: Ser-249 TP53 mutation (249(Ser)) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249(Ser) mutation in HCC from patients in Brazil. METHODS: We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249(Ser) mutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR. RESULTS: 249(Ser) mutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249Ser mutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249(Ser) mutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249(Ser) mutation (OR = 2.415, 95% CI = 1.001 - 5.824, p = 0.05). The mean size of 249(Ser) HCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249(Ser) mutation. CONCLUSION: Our results indicate that 249(Ser) mutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.

CFTR polymorphisms in patients with alcoholic chronic pancreatitis.

INTRODUCTION: Pancreas susceptibility to alcohol is variable and only 5-10% of chronic alcohol abusers develop chronic pancreatitis; the role of genetic factors in this process is unknown. The CFTR gene encodes a protein that acts on epithelial cells and plays a key role in normal exocrine pancreatic function. METHODS: This study investigated the frequency of polymorphisms in intron 8 of the CFTR gene in patients with alcoholic chronic pancreatitis. Three groups of patients were studied: group A - 68 adult alcoholics with a diagnosis of chronic pancreatitis; group B - 68 adult alcoholics without pancreatic disease or liver cirrhosis and group C - 104 healthy nonalcoholic adults. RESULTS: T5/T7 genotype was more frequent in group A (11.8%) than in group B (2.9%) (p = 0.0481), and there was no statistical difference when groups A and C (5.8%) were compared (p = 0.1317). The haplotype combination (TG)10-T7/(TG)11-T7 was more frequent in groups B (23.5%) and C (20.2%) than in group A (7.3%) (p = 0.0080 and 0.0162). CONCLUSION: There are differences when these three groups are compared and individuals with T5/T7 genotype might have a greater risk of developing chronic pancreatitis when they become chronic alcoholics.

Nodules less than 20 mm and vascular invasion are predictors of survival in small hepatocellular carcinoma.

BACKGROUND: The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil. METHODS: Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model. RESULTS: The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: 1 to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P=0.016), Child-Pugh classification (P=0.007), alpha-fetoprotein level (P=0.006), number of nodules (P=0.041), tumor diameter (P=0.009), and vascular invasion (P<0.0001) were significant predictors of survival. Cox regression analysis identified vascular invasion (relative risk=14.60, confidence interval 95%=3.3-64.56, P<0.001) and tumor size >20 mm (relative risk=2.14, confidence interval 95%=1.07-4.2, P=0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. CONCLUSIONS: Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors of up to 20 mm diameter is related to increased survival.

HIGHER VALUES IN LIVER ELASTOGRAPHY AND MELD SCORE ARE MORTALITY PREDICTORS ON LIVER TRANSPLANT WAITING LIST.

BACKGROUND: Liver elastography have been reported in hepatocellular carcinoma (HCC) with higher values; however, it is unclear to identify morbimortality risk on liver transplantation waiting list. AIM: To assess liver stiffness, ultrasound and clinical findings in cirrhotic patients with and without HCC on screening for liver transplant and compare the morbimortality risk with elastography and MELD score. METHOD: Patients with cirrhosis and HCC on screening for liver transplant were enrolled with clinical, radiological and laboratory assessments, and transient elastography. RESULTS: 103 patients were included (without HCC n=58 (66%); HCC n=45 (44%). The mean MELD score was 14.7±6.4, the portal hypertension present on 83.9% and the mean transient elastography value was 32.73±22.5 kPa. The median acoustic radiation force impulse value of liver parenchyma was 1.98 (0.65-3.2) m/s and 2.16 (0.59-2.8) m/s in HCC group. The HCC group was significantly associated with HCV infection (OR 26.84; p<0.0001), higher levels of serum alpha-fetoprotein (OR 5.51; p=0.015), clinical portal hypertension (OR 0.25; p=0.032) and similar MELD score (p=0.693). The area under the receiver operating characteristics (AUROC) showed sensitivity and specificity for serum alpha-fetoprotein (cutoff 9.1 ng/ml), transient elastography value (cutoff value 9 kPa), and acoustic radiation force impulse value (cutoff value 2.56 m/s) of 50% and 86%, 92% and 17% and 21% and 92%, respectively. The survival group had a mean transient elastography value of 31.65±22.2 kPa vs. 50.87±20.9 kPa (p=0.098) and higher MELD scores (p=0.035). CONCLUSION: Elastography, ultrasound and clinical findings are important non-invasive tools for cirrhosis and HCC on screening for liver transplant. Higher values in liver elastography and MELD scores predict mortality.

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C.

OBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

Altos valores de rigidez hepática desempenham um papel importante na estratificação do risco de carcinoma hepatocelular em pacientes cirróticos com vírus C / High values of liver stiffness play an important role in stratifying the risk of hepatocellular carcinoma in cirrhotic hepatitis c patients

ABSTRACT Background: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. Methods: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. Results: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). Conclusion: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.

RESUMO Contexto: O carcinoma hepatocelular (CHC) é o tumor maligno hepático mais comum, e a cirrose é o principal fator de risco para o seu desenvolvimento. Objetivo: Avaliar o papel da medição da rigidez hepática por elastografia transitória (ET) como fator de risco para ocorrência de CHC em uma coorte prospectiva de pacientes brasileiros com cirrose por vírus da hepatite C (VHC). Métodos: Um total de 99 pacientes com VHC e medida de rigidez hepática ≥12 kilopascals (kPa) foram incluídos consecutivamente, entre 2011 e 2016. As variáveis do baseline foram avaliadas e a ocorrência de CHC foi documentada. Os testes de Kaplan-Meier e log-rank, além das análises uni e multivariadas de Cox avaliaram a associação entre as variáveis e os resultados clínicos. Resultados: A média de idade foi de 57,8±10,6 anos. Vinte (20,2%) pacientes desenvolveram CHC, num período médio de seguimento de 3,3 anos. Na análise de regressão logística univariada, as variáveis associadas à ocorrência de CHC foram: contagem de plaquetas mais baixa (P=0,0446), valores séricos mais elevados de alfa-fetoproteína (P=0,0041) e de bilirrubina (P=0,0008), maior pontuação do escore MELD (P=0,0068) e valores mais altos de rigidez hepática por ET (P=0,0354). A medição da rigidez hepática por ET foi independentemente associada ao desenvolvimento de CHC, e o melhor valor de corte para maior risco de CHC foi >21,1kPa (HR: 5,548; IC95%: 1,244-24,766; P=0,025). Conclusão: Um alto valor de rigidez hepática está relacionado substancialmente a um risco aumentado de ocorrência de CHC em pacientes brasileiros com cirrose por HCV.

Concordance of non-invasive mechanical and serum tests for liver fibrosis evaluation in chronic hepatitis C.

AIM: To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum markers (SM) for liver fibrosis evaluation in chronic hepatitis C. METHODS: Between 2012 and 2014, 81 consecutive hepatitis C virus (HCV) patients had METAVIR score from liver biopsy compared with concurrent results from LSM [transient elastography (TE) [FibroScan®/ARFI technology (Virtual Touch®)] and SM [FIB-4/aspartate aminotransferase-to-platelet ratio index (APRI)]. The diagnostic performance of these tests was assessed using receiver operating characteristic curves. The optimal cut-off levels of each test were chosen to define fibrosis stages F ≥ 2, F ≥ 3 and F = 4. The Kappa index set the concordance analysis. RESULTS: Fifty point six percent were female and the median age was 51 years (30-78). Fifty-six patients (70%) were treatment-naïve. The optimal cut-off values for predicting F ≥ 2 stage fibrosis assessed by TE were 6.6 kPa, for acoustic radiation force impulse (ARFI) 1.22 m/s, for APRI 0.75 and for FIB-4 1.47. For F ≥ 3 TE was 8.9 kPa, ARFI was 1.48 m/s, APRI was 0.75, and FIB-4 was 2. For F = 4, TE was 12.2 kPa, ARFI was 1.77 m/s, APRI was 1.46, and FIB-4 was 3.91. The APRI could not distinguish between F2 and F3, P = 0.92. The negative predictive value for F = 4 for TE and ARFI was 100%. Kappa index values for F ≥ 3 METAVIR score for TE, ARFI and FIB-4 were 0.687, 0.606 and 0.654, respectively. This demonstrates strong concordance between all three screening methods, and moderate to strong concordance between them and APRI (Kappa index = 0.507). CONCLUSION: Given the costs and accessibility of LSM methods, and the similarity with the outcomes of SM, we suggest that FIB-4 as well as TE and ARFI may be useful indicators of the degree of liver fibrosis. This is of particular importance to developing countries.

Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls.

OBJECTIVE: This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. METHODS: The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. RESULTS: Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P < 0.01). The difference in smoking frequency was not significant between the patients with idiopathic pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. CONCLUSIONS: Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis.

Interferon lambda and hepatitis C virus core protein polymorphisms associated with liver cancer.

BACKGROUND: Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm. METHOD OF STUDY: the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC). RESULTS: the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054). CONCLUSIONS: the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development.

Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review.

BACKGROUND AND AIMS: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrum of pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. METHODS: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of São Paulo School of Medicine and Hospital das Clínicas, Brazil. RESULTS: Seven cases were included. The mean age of patients was 62.1±10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related to portal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. CONCLUSIONS: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the presence of HBV and HCV infections, likely acts as a cofactor for the hepatic lesion and potentiates injury.

Clinical and epidemiological aspects of hepatocellular carcinoma in Brazil.

The global hepatocellular carcinoma (HCC) incidence is widely variable, depending on geographic region and the prevalence of major risk factors. In Brazil, two large multicentre retrospective studies were performed to investigate clinical and epidemiological aspects of HCC. In the first study, performed in 1997, HCC was found in cirrhotic livers in 71% of cases. Chronic alcoholism was present in 36% of cases, chronic hepatitis B in 35% and hepatitis C in 25%. In a 2010 survey, cirrhosis was present in 98% of cases and HCV was the main aetiology (54%). Differences in HBV prevalence were found among regions. Selection of HCC treatment depends on tumour burden, liver function and performance status. Liver transplantation (LT) is the best available curative treatment for HCC in its early stage and with compromised liver function. After modifications in priority policy, the number of patients with early HCC submitted for LT has increased in the past 5 years in Brazil. Chemoembolization is the most common initial HCC therapy in early and intermediate stages of HCC in Brazil.