Validation and Performance of FibroScan®-AST (FAST) Score on a Brazilian Population with Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIM: FAST score has a good performance for diagnosing the composite of NASH + NAS ≥ 4 + F ≥ 2. However, it has not been evaluated in Latin American individuals with nonalcoholic fatty liver disease (NAFLD). We aimed to analyze the performance of the FAST score in a Brazilian NAFLD population. METHODS: Cross-sectional study was held in ≥ 18 years NAFLD patients diagnosed by ultrasonography and submitted to liver biopsy (LB). Liver stiffness (LSM) and CAP measurements were performed with FibroScan®, using M (BMI < 32 kg/m2) or XL probes. Area under receiver operating characteristic (AUROC) curves were calculated as well as sensitivity (S), specificity (Spe), positive predictive value (VPP) and negative predictive value (NPV) for the previously established FAST score cut-offs. RESULTS: Among 287 patients included (75% female; mean age 55 ± 10 years), NASH + NAS ≥ 4 + F ≥ 2 was reported in 30% of LB. For the FAST cut-off of 0.35, the S and NPV to rule out NASH + NAS ≥ 4 + F ≥ 2 were 78.8% and 87.8%, respectively. Regarding the cut-off of 0.67, the Spe and PPV to rule-in NASH + NAS ≥ 4 + F ≥ 2 were 89.1%, 61.8%, respectively. The AUROC of FAST for all included patients was 0.78 (95% CI 0.72-0.84) and for those with ≥ 32 kg/m2 was 0.81 (95% CI 0.74-0.88). CONCLUSION: FAST score has a good performance in a Brazilian NAFLD population, even in patients with higher BMI when the XL probe is adopted. Therefore, FAST can be used as a noninvasive screening tool mainly for excluding the diagnosis of progressive NASH, reducing the number of unnecessary liver biopsies.

Efficacy and safety of glecaprevir/pibrentasvir in treatment-naïve adults with chronic hepatitis C virus genotypes 1-6 in Brazil.

INTRODUCTION AND OBJECTIVES: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. PATIENTS AND METHODS: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1-6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. RESULTS: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0-99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. CONCLUSIONS: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03219216.

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil.

INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. MATERIALS AND METHODS: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). RESULTS: 3939 patients (60% males, mean age 58±10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. CONCLUSION: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.

Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

Validation of the Brazilian version of Chronic Liver Disease Questionnaire.

PURPOSE: The aim of this study was to validate the Chronic Liver Disease Questionnaire (CLDQ) for use in Brazilian population. METHOD: A total of 200 patients with chronic liver disease and varying disease severity answered a socio-demographic questionnaire, t CLDQ, and the Medical Outcome Study Short Form 36 (SF-36). Patients returned in 1-15 days to answer CLDQ again. The Cronbach's alpha of the total CLDQ score was 0.95 and fluctuated between 0.69 and 0.83 in its six domains. RESULTS: The intra-class correlation between total CLDQ scores in two evaluations was 0.97 and in all domains was >0.93. CLDQ was moderately correlated with the SF-36, 0.63 (total CLDQ vs. vitality, SF-36), 0.62 (CLDQ and mental health, SF-36), 0.62 (preoccupation, CLDQ, vs. General Health, SF-36), 0.59 (fatigue, CLDQ, vs. vitality, SF-36), 0.59 (activity, CLDQ, vs. vitality, SF-36), and 0.59 (fatigue, CLDQ, vs. mental health, SF-36). The highest scores were found in non-cirrhotic group. Child A patients had higher average scores than Child B and C groups in all domains, while patients with MELD <15 scored higher than patients with MELD ≥15. CONCLUSION: CLDQ-BR was validated in Brazilian population and was appropriate for use in patients with liver disease of different etiologies and degrees of severity.

BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR SYSTEMIC TREATMENT OF HEPATOCELLULAR CARCINOMA.

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.

IS HOMEOSTASIS MODEL ASSESSMENT FOR INSULIN RESISTANCE >2.5 A DISTINGUISHED CRITERIA FOR METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE IDENTIFICATION?

BACKGROUND: Insulin resistance (IR), assessed by different criteria, is an important factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). More recently with the characterization of this metabolic dysfunction-associated fatty liver disease (MAFLD), one of the proposed criteria for this diagnosis has been the determination of the homeostasis model assessment-insulin resistance (HOMA-IR). OBJECTIVE: The purpose of this study was to evaluate the relationship of HOMA-IR>2.5 with clinical, metabolic, biochemical and histological data obtained in non-diabetic patients diagnosed with NAFLD by liver biopsy. METHODS: Cross-sectional, retrospective study was carried out with data from 174 adult individuals of both genders with non-diabetics NAFLD, without obvious signs of portal hypertension. The body mass index (BMI) was classified according to the World Health Organization (1998), and the metabolic syndrome by the criteria of NCEP-ATP-III. Biochemical tests were evaluated using an automated method and insulinemia through immunofluorometric assay. Histological findings were classified according to Kleiner et al. (2005). RESULTS: The mean age of the studied population was 53.6±11.2 years, with 60.3% being female. The average BMI was 30.3 kg/m2 and 75.9% of the patients had increased waist circumference. Among evaluated metabolic parameters, there was a higher prevalence of metabolic syndrome (MS) in patients with HOMA-IR>2.5, with no statistical difference in relation to BMI between studied groups. Values of liver enzymes and serum ferritin were significantly higher in patients with this marker of IR, who had a higher prevalence of non-alcoholic steatohepatitis (NASH) and advanced liver fibrosis. In the multivariate analysis, the clinical diagnosis of MS, hyperferritinemia and the presence of NASH in the liver biopsy were the factors independently associated with the presence of altered HOMA-IR. CONCLUSION: HOMA-IR values >2.5 identify patients with NAFLD with distinct clinical and metabolic characteristics and with a greater potential for disease progression, which validates this parameter in the identification of patients with MAFLD.

OBSTRUCTIVE SLEEP APNEA SYNDROME RISK IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH OBESITY AND PRESENCE OF NASH.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and refers to a wide spectrum of histological abnormalities ranging from simple steatosis (HE) to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. OBJECTIVE: To assess the risk of obstructive sleep apnea syndrome (OSAS) and relating it to demographic, biochemical and histological data in patients with non-alcoholic fatty liver disease. METHODS: Cross-sectional cohort study in individuals with biopsy-proven NAFLD. Anthropometric and biochemical parameters, presence of metabolic syndrome and insulin resistance were evaluated. The Berlin Questionnaire (BQ) was applied to assess the risk of apnea and a food record was requested. Based on the BQ, participants were classified as high or low risk for OSAS. In the correlation of sleep apnea with the severity of NAFLD, presence of nonalcoholic steatohepatitis (NASH) and the degree of liver fibrosis were evaluated. Statistical analysis used the chi-square test, Student's t and bivariate logistic regression; values were expressed as mean ± standard deviation. This research project was approved by the Ethics Committee. RESULTS: Regarding the parameters evaluated, significant differences were observed between the groups in terms of body mass index (BMI), waist and neck circumference. In the histological evaluation, patients classified as high risk were more likely to have fibrosis and NASH. In bivariate regression, the BMI, presence of fibrosis and steatohepatitis in the biopsy were independently associated with an elevated risk of the syndrome. CONCLUSION: A high prevalence of risk for OSAS was observed in the studied group, with a higher risk being independently associated with BMI and presence of steatohepatitis, suggesting that it is a factor associated with the severity of the disease.

Factors associated with nutritional status in liver transplant patients who survived the first year after transplantation.

BACKGROUND AND AIMS: Most studies published focus on the evaluation of the impact of nutritional status on the morbidity and mortality during the immediate postoperative period or on the short-term evolution of liver transplant patients. The aim of the study was to evaluate long-term trends in nutritional status. METHODS: Seventy patients consecutively submitted to liver transplantation were studied. Nutritional assessment was performed the day before transplantation and the 45, 90, 180 and 365 days after transplantation, consisting of determination of dietary intake, anthropometric and biochemical analysis. RESULTS: Sixty-nine percent of the patients presented with malnutrition on the day before liver transplantation, decreasing to 44% at end of the first year. The prevalence of protein-calorie malnutrition (PCM) was 63% at 90 days post-transplant. A significant difference of PCM was observed between patients with cirrhosis and non-cirrhotic disease (53.6% x 100%) at 90 days post-transplant. The pre-transplant nutritional diagnosis and 90-day calorie intake were identified as variables independently associated with nutritional status at 90 days post-transplant. The variables independently associated with nutritional status in the 1-year assessment were pre-transplant PCM and 365-day calorie requirements. CONCLUSION: No influence on nutritional status was observed for peri- or postoperative factors after 3 or 12 months of follow up. As expected, dietary factors, especially adequate calorie intake, were always associated with nutritional status during all periods analyzed.

Evaluation of hepatic fibrosis by elastography in patients with schistosomiasis mansoni.

BACKGROUND: Periportal fibrosis is associated with the main complications of schistosomiasis mansoni. The usefulness of hepatic transient elastography (TE) in its evaluation remains to be clarified. METHODS: We conducted a cross-sectional study of schistosomal patients, where the measurements obtained by FibroScan TE were correlated with the degree of liver fibrosis according to the Niamey sonographic protocol, adopted as the gold standard, and its performance was calculated as the area under the receiver operating characteristics curve (AUROC). RESULTS: A total of 117 of 141 adult schistosomiasis patients from endemic areas were selected between May and August 2015. Applying the Niamey protocol, the patients were regrouped into absent fibrosis (A; 34.2%), mild to moderate fibrosis (MM; 27.4%) and intense fibrosis (I; 38.5%). The median of the TE values in the patients of group A was 4.7 kPa, the group MM 9.3 kPa and the group I 10.3 kPa. There was a difference in the TE values between the group A and the groups MM and I (p < 0.05). The TE also presented strong and direct correlation with the clinical form (r ≥ 0.77). The AUROC value to define the presence of fibrosis was 0.92 and for significant fibrosis was 0.79, with cut-offs of 6.1 kPa and 8.9 kPa, respectively. CONCLUSIONS: In this study, the TE was effective in the diagnosis of schistosomal fibrosis, being able to identify the advanced forms of the disease and thus predict the risk of clinical complications in endemic regions.

PERIPHERAL BLOOD ENDOTOXIN LEVELS ARE NOT ASSOCIATED WITH SMALL INTESTINAL BACTERIAL OVERGROWTH IN NONALCOHOLIC FATTY LIVER DISEASE WITHOUT CIRRHOSIS.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease worldwide. Approximately 20% of individuals with NAFLD develop nonalcoholic steatohepatitis (NASH), which is associated with increased risk of cirrhosis, portal hypertension, and hepatocellular carcinoma. Intestinal microflora, including small intestinal bacterial overgrowth (SIBO), appear to play an important role in the pathogenesis of the disease, as demonstrated in several clinical and experimental studies, by altering intestinal permeability and allowing bacterial endotoxins to enter the circulation. OBJECTIVE: To determine the relationship between SIBO and endotoxin serum levels with clinical, laboratory, and histopathological aspects of NAFLD and the relationship between SIBO and endotoxin serum levels before and after antibiotic therapy. METHODS: Adult patients with a histological diagnosis of NAFLD, without cirrhosis were included. A comprehensive biochemistry panel, lactulose breath test (for diagnosis of SIBO), and serum endotoxin measurement (chromogenic LAL assay) were performed. SIBO was treated with metronidazole 250 mg q8h for 10 days and refractory cases were given ciprofloxacin 500 mg q12h for 10 days. RESULTS: Overall, 42 patients with a histopathological diagnosis of NAFLD were examined. The prevalence of SIBO was 26.2%. Comparison of demographic and biochemical parameters between patients with SIBO and those without SIBO revealed no statistically significant differences, except for use of proton pump inhibitors, which was significantly more frequent in patients with positive breath testing. The presence of SIBO was also associated with greater severity of hepatocellular ballooning on liver biopsy. Although the sample, as a whole, have elevated circulating endotoxin levels, we found no significant differences in this parameter between the groups with and without SIBO. Endotoxin values before and after antibiotic treatment did not differ, even on paired analysis, suggesting absence of any relationship between these factors. Serum endotoxin levels were inversely correlated with HDL levels, and directly correlated with triglyceride levels. CONCLUSION: Serum endotoxin levels did not differ between patients with and without SIBO, nor did these levels change after antibacterial therapy, virtually ruling out the possibility that elevated endotoxinemia in non-cirrhotic patients with NAFLD is associated with SIBO. Presence of SIBO was associated with greater severity of ballooning degeneration on liver biopsy, but not with a significantly higher prevalence of NASH. Additional studies are needed to evaluate the reproducibility and importance of this finding in patients with NAFLD and SIBO.

Underlying mechanism of portal hypertensive gastropathy in cirrhosis: a hemodynamic and morphological approach.

BACKGROUND AND AIM: Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis. METHODS: Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis. RESULTS: The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 +/- 5.9 mmHg) and severe PHG (16.9 +/- 6.5 mmHg; P = 0.80) or between patients who did not have (15.2 +/- 8.0 mmHg) and those who had PHG (16.3 +/- 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index (P = 0.53 and 0.34, respectively), Child-Pugh classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and 0.62, respectively). CONCLUSIONS: The present data show no correlation between the presence or the severity of PHG and portal pressure, Child-Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.

N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL.

BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.

Is there a place for serum laminin determination in patients with liver disease and cancer?

Laminin is a glycoprotein which has an important role in the mechanism of fibrogenesis and is, thus, related to hepatic fibrosis in addition to presenting increased levels in several types of neoplasias. However, its determination is not routinely considered in the study of hepatic fibrosis. In this review, the authors critically comment on the role of this glycoprotein compared to other markers of fibrosis through non-invasive procedures (Fibroscan). They also consider its clinical investigational potential and believe that the continuation of these investigations might contribute to a better understanding of the fibrogenic mechanism, which could in turn either lead to the identification of patients at risk of developing fibrosis non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) or at least be used as an indicator for hepatic biopsy in such patients. Finally, the authors believe that serum laminin determination might contribute to the diagnosis of epithelial tumor metastasis and peritoneal carcinomatosis.

DOES INSULIN RESISTANCE IMPAIR THE VIROLOGICAL RESPONSE TO PEGINTERFERON/RIBAVIRIN IN CHRONIC HEPATITIS C GENOTYPE 3 PATIENTS?

BACKGROUND: Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE: To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS: A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS: Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION: In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.

Atualização das Recomendações da Sociedade Brasileira de Hepatologia para o Tratamento Sistêmico do Carcinoma Hepatocelular / Brazilian society of hepatology updated recommendations for systemic treatment of hepatocellular carcinoma

ABSTRACT 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.

RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.

Cryoglobulinemia in chronic hepatitis C: clinical aspects and response to treatment with interferon alpha and ribavirin.

INTRODUCTION: The main extra-hepatic manifestation of hepatitis C is mixed cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among patients with chronic hepatitis C (CHC), to correlate its presence to host and virological variables and to the response to combined therapy with interferon-alpha and ribavirin. CASUISTIC AND METHODS: 202 CHC naive patients (136 with chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the presence of cryoglobulins. Cryoprecipitates were characterized by immunoelectrophoresis and classified according to the Brouet's criteria. RESULTS: The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major clinical manifestation of the disease. Even though type III MC was more frequent (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis (RR=2.073; IC95%=1.029-4.179; p=0.041), and age of the patients (RR=1.035; IC95%=1.008-1.062; p=0.01) were independently associated with the presence of cryoglobulins. No relationship was found with viral load and genotype. 102 patients were treated with interferon alpha and ribavirin. Among these, 31 had MC. Sustained virological response (around 30%) was similar in patients with and without MC (p=0.971). CONCLUSION: MC represents a prevalent complication in patients with CHC, specially older and cirrhotic patients. Only 24% of these patients show clinical manifestation of the disease, specially those with type II MC. The presence of MC did not affect the response to therapy.

[Insulin resistance in chronic hepatitits C]. / Importância da resitência insulínica na hepatite C crônica.

OBJECTIVE: To revise the importance of insulin resistance in the development of chronic hepatitis C and its interference in the response to the antiviral treatment of these patients. DATA SOURCE: Bibliographic revision of published papers in the MEDLINE and the authors data. DATA SYNTHESIS: In the last years several published papers have demonstrated an important relationship between insulin resistance and chronic hepatitis C. Increased prevalence of type 2 diabetes mellitus, the development of hepatic steatosis (specially in non-3 genotype), a more rapid progression of hepatic disease and reduction in the sustained virological response to treatment with pegylated interferon plus ribavirin have been associated with insulin resistance in patients infected with HCV. The mechanism implied in the insulin resistance is the enhanced production of tumor necrosis factor by the HCV core. Tumor necrosis factor affects insulin receptor substrate phosphorylation, resulting in decreased glucose uptake and compensatory hyperinsulinemia. Increased liver iron accumulation and modification in the levels of adipocytokinemia can have an additional effect on insulin sensitivity in chronic C hepatitis. CONCLUSIONS: Diagnosing and treating insulin resistance in patients with chronic hepatitis C could not only avoid complications but also prevent disease progression and increased the sustained virological rate to treatment with pegylated interferon plus ribavarin.

O risco de síndrome de apneia obstrutiva do sono em pacientes com doença hepática gordurosa não alcoólica está associado à obesidade e à presença de NASH / Obstructive sleep apnea syndrome risk in patients with non-alcoholic fatty liver disease is associated with obesity and presence of nash

ABSTRACT Background: Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and refers to a wide spectrum of histological abnormalities ranging from simple steatosis (HE) to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Objective: To assess the risk of obstructive sleep apnea syndrome (OSAS) and relating it to demographic, biochemical and histological data in patients with non-alcoholic fatty liver disease. Methods: Cross-sectional cohort study in individuals with biopsy-proven NAFLD. Anthropometric and biochemical parameters, presence of metabolic syndrome and insulin resistance were evaluated. The Berlin Questionnaire (BQ) was applied to assess the risk of apnea and a food record was requested. Based on the BQ, participants were classified as high or low risk for OSAS. In the correlation of sleep apnea with the severity of NAFLD, presence of nonalcoholic steatohepatitis (NASH) and the degree of liver fibrosis were evaluated. Statistical analysis used the chi-square test, Student's t and bivariate logistic regression; values were expressed as mean ± standard deviation. This research project was approved by the Ethics Committee. Results: Regarding the parameters evaluated, significant differences were observed between the groups in terms of body mass index (BMI), waist and neck circumference. In the histological evaluation, patients classified as high risk were more likely to have fibrosis and NASH. In bivariate regression, the BMI, presence of fibrosis and steatohepatitis in the biopsy were independently associated with an elevated risk of the syndrome. Conclusion: A high prevalence of risk for OSAS was observed in the studied group, with a higher risk being independently associated with BMI and presence of steatohepatitis, suggesting that it is a factor associated with the severity of the disease.

RESUMO Contexto: A doença hepática gordurosa não alcoólica (DHGNA) é a forma mais comum de doença hepática e se refere a um amplo espectro de anormalidades histológicas que variam de esteatose simples a esteato-hepatite não alcoólica (EHNA), fibrose, cirrose e carcinoma hepatocelular. Objetivo: Avaliar o risco de síndrome da apneia obstrutiva do sono (SAOS) e relacioná-lo com dados demográficos, bioquímicos e histológicos em pacientes com doença hepática gordurosa não alcoólica. Métodos: Estudo de coorte transversal em indivíduos com DHGNA comprovada por biópsia. Foram avaliados parâmetros antropométricos e bioquímicos, presença de síndrome metabólica e resistência à insulina. O Questionário de Berlim (QB) foi aplicado para avaliar o risco de apneia e um registro alimentar foi solicitado. Com base no QB, os participantes foram classificados como de alto ou baixo risco para SAOS. Na correlação da apneia do sono com a gravidade da DHGNA, avaliou-se a presença de EHNA e o grau de fibrose hepática. Na análise estatística foram utilizados: o teste qui-quadrado, t de Student e regressão logística bivariada; os valores foram expressos como média ± desvio padrão. Este projeto de pesquisa foi aprovado pelo Comitê de Ética. Resultados: Em relação aos parâmetros avaliados, foram observadas diferenças significativas entre os grupos em relação ao índice de massa corporal (IMC), cintura e circunferência do pescoço. Na avaliação histológica, os pacientes classificados como de alto risco tiveram maior chance de apresentar fibrose e EHNA. Na regressão bivariada, o IMC, a presença de fibrose e esteato-hepatite na biópsia foram independentemente associados a um risco elevado da síndrome. Conclusão: Observou-se alta prevalência de risco para SAOS no grupo estudado, sendo o maior risco associado de forma independente ao IMC e à presença de esteato-hepatite, sugerindo que seja um fator associado à gravidade da doença.

Avaliação audiológica em pacientes com hepatite C crônica tratados por antivirais de ação direta / Audiological evaluation in patients with chronic hepatitis C treated by direct-action antivirals

RESUMO Objetivo Verificar se o tratamento com os antivirais de ação direta para a hepatite C provocam efeitos adversos na audição. Métodos A casuística foi composta por 16 indivíduos portadores do vírus da hepatite C, de ambos os gêneros, com média de idade de 51 anos. Foram excluídos do grupo indivíduos com perda auditiva do tipo condutiva ou mista e que apresentassem fatores de risco para perda auditiva. A avaliação foi realizada em dois momentos: antes do uso dos antivirais de ação direta e após o término do tratamento de três meses. Incluiu os seguintes procedimentos: anamnese, inspeção do meato acústico externo, audiometria tonal liminar, limiar de recepção de fala, índice de reconhecimento de fala, medidas de imitância acústica e emissões otoacústicas evocadas por estímulo transiente e produto de distorção. Resultados: Houve baixa ocorrência de zumbido e vertigem. Não houve diferença estatisticamente significativa entre os resultados da avaliação pré-tratamento e pós-tratamento. Conclusão O tratamento com antivirais de ação direta contra o vírus da hepatite C não provocou efeitos adversos na função auditiva.

ABSTRACT Purpose To verify whether treatment with hepatitis C direct-acting antivirals has adverse effects on hearing. Methods The sample consisted of 16 individuals with hepatitis C virus, of both sexes, with an average age of 51 years. Individuals with conductive or mixed hearing loss who presented risk factors for hearing loss were excluded from the group. The evaluation was carried out in two moments: before the use of direct-acting antivirals and after the three-month treatment. It included the following procedures: anamnesis, external auditory canal inspection, pure tone audiometry, speech reception threshold, speech recognition index, acoustic immittance measures and transient and distortion product otoacoustic emissions. Results There was a low incidence of tinnitus and vertigo. There was no statistically significant difference between the results of the pre- and post-treatment assessment. Conclusion The treatment with direct-acting antivirals against the hepatitis C virus did not cause any adverse effects on hearing function.