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)].

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.

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.

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.

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.

Higher values in liver elastography and meld score are mortality predictors on liver transplant waiting list / Valores mais altos na elastografia do fígado e pontuação meld são preditores de mortalidade na lista de espera do transplante de fígado

ABSTRACT 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.

RESUMO Racional: A elastografia hepática tem sido relatada nos carcinomas hepatocelulares (CHC); porém, não é claro identificar o risco de morbimortalidade na lista de transplante hepático. Objetivo: Avaliar a morbimortalidade com elastografia transitória e escore MELD. Método: Pacientes adultos com cirrose na triagem para transplante de fígado foram incluídos no estudo. Resultados: Foram incluídos 103 pacientes (sem CHC n=58 (66%), CHC n=45 (44%). O escore MELD médio foi de 14,7±6,4, a hipertensão portal foi de 83,9% e o valor médio de elastografia transitória foi de 32,73±22,5 kPa. O valor médio de ARFI (Impulsão de Força de Radiação Acústica) do parênquima hepático foi de 1,98 (0,65-3,2) m/s e 2,16 (0,59-2,8) m/s no grupo CHC. O grupo CHC foi significativamente associado à infecção por vírus da hepatite C (OR 26,84, p<0,0001), níveis mais altos de alfa-feto proteína sérica (OR 5,51; p=0,015), hipertensão portal clínica (OR 0,25; p=0,032) e pontuação MELD semelhante (p=0,693). Os valores de AUROCs (Area Under the Receiver Operating Characteristics) mostraram sensibilidade e especificidade para a alfa-feto proteína sérica (limite de 9,1 ng/ml), valor elastografia transitória (valor de corte 9 kPa) e valor ARFI (valor de corte 2,56 m/s) de 50% e 86%, 92% e 17% e 21% e 92%, respectivamente. O grupo de sobrevivência apresentou valor elastografia transitória médio de 31,65±22,2 kPa vs. 50,87±20,9 kPa (p=0,098) e valores mais elevados de MELD (p=0,035). Conclusão: Valores mais elevados na elastografia do fígado e nos escores MELD predizem a mortalidade.