Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>;20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.Federal University of São PauloSanta Casa de Misericórdia Gastroenterology ServiceFederal University of ParáFederal University of Juiz de ForaSão Paulo University Medical School of Ribeirão PretoEmílio Ribas InstituteFederal University of Minas GeraisMedical School of São José do Rio PretoFederal University of AlagoasFederal University of Santa CatarinaFederal University of BahiaTropical Medicine FundationOswaldo Cruz HospitalFederal University of ParaíbaRocheUNIFESPSciEL

Utility and limitations of APRI and FIB4 to predict staging in a cohort of nonselected outpatients with hepatitis C

Background. Chronic hepatitis C(CHC) staging is important for therapeutic decision-making. Identification of noninvasive markers can provide alternatives to liver biopsy.Aim. To assess the value of APRI and FIB4 for CHC fibrosis staging in a cohort of nonselected outpatients from a referral center in Sao Paulo, Brazil.Material and methods. Medical records of 798 adult outpatients were analyzed retrospectively. For calculations of APRI and FIB4, the original descriptions were considered, and markers were compared with degree of liver injury.Results. Overall, 49.3% of participants were female, and mean age was 56.9 ± 12.5 years. Genotype 1 was predominant (71.7vs. 23.7% genotype 3); 64% had significant fibrosis, 44% had advanced fibrosis, and 28% had cirrhosis. The areas under the receiver operating curve for significant fibrosis, advanced fibrosis, and cirrhosis, respectively, were 0.809, 0.819, and 0.815 for the APRI marker and 0.803, 0.836 and 0.852 for FIB4. Using the recommended cut off values, approximately 30-40% of the patients could not be classified. In the remainder, either APRI or FIB4 alone correctly diagnosed 80-85% of cases. Concomitant or consecutive use of both APRI and FIB4 increased the number of the cases correctly diagnosed only slightly, but also increased the number of patients not classified within the cutoff values.Conclusions. In conclusion, use of the APRI or FIB4 markers for detection of hepatic fibrosis may be a viable alternative at referral centers for treatment of CHC in low- and middleincome countries. Despite relatively good accuracy, a significant number of patients could not be assessed by these methods

Noninvasive serum markers in the diagnosis of structural liver damage in chronic hepatitis C virus infection

Aim: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST to platelet ratio index (APRI) and gamma-glutamyltransferase (GGT) levels to predict the intensity of hepatic fibrosis in patients with CHC.Patients and methods: in a total of 206 hepatitis C virus RNA-positive biopsied patients, AST, ALT, GGT levels, platelet count and serum HA concentration were determined. the APRI was calculated as the ratio of AST to platelets.Results: HA levels were best correlated with disease stage (r=-0.694; P < 0.001). in the diagnosis of significant fibrosis (F2-F4), HA levels [AUC=0.879, 95% CI (0.832-0.927)] and APRI [AUC=0.824 (0.772-0.903)] were the markers with the best diagnostic accuracy. These parameters also best identified the presence of cirrhosis (F4), with an AUC of 0.908 (0.868-0.949) for HA and of 0.837 (0.772-0.903) for APRI.Conclusions: Serum HA was the parameter that alone presented the best diagnostic accuracy in the assessment of hepatic fibrosis in CHC. the APRI showed a better diagnostic sensitivity than GGT levels or the AST/ALT ratio. Its simple determination and low cost make this index a valid alternative for the noninvasive staging of CHC.Universidade Federal de São Paulo, Dept Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Mol Biol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Mol Biol, São Paulo, BrazilWeb of Scienc

NONALCOHOLIC FATTY LIVER DISEASE BRAZILIAN SOCIETY OF HEPATOLOGY CONSENSUS

ABSTRACT The prevalence of obesity-related metabolic syndrome has rapidly increased in Brazil, resulting in a high frequency of nonalcoholic fatty liver disease, that didn't receive much attention in the past. However, it has received increased attention since this disease was identified to progress to end-stage liver diseases, such as cirrhosis and hepatocellular carcinoma. Clinical practice guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease have not been established in Brazil. The Brazilian Society of Hepatology held an event with specialists' members from all over Brazil with the purpose of producing guideline for Nonalcoholic Fatty Liver Disease based on a systematic approach that reflects evidence-based medicine and expert opinions. The guideline discussed the following subjects: 1-Concepts and recommendations; 2-Diagnosis; 3-Non-medical treatment; 4-Medical treatment; 5-Pediatrics - Diagnosis; 6-Pediatrics - Non-medical treatment; 7-Pediatrics - Medical treatment; 8-Surgical treatment

Cardiometabolic disorders, inflammation and the incidence of non-alcoholic fatty liver disease: A longitudinal study comparing lean and non-lean individuals.

BackgroundThere is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.MethodsWe analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (&lt;150 minutes/week of moderate activity). We further assessed the risk of NAFLD with elevations in waist circumference and high sensitivity C-reactive protein (HsCRP).ResultsOver 15,580 person-years (PY) of follow-up, the incidence rate of NAFLD was 7.7 per 100 PY. In multivariate analysis adjusting for likely confounders, AD was associated with a 72% greater risk of NAFLD (IRR: 1.72 [95% CI:1.32-2.23]). Elevated blood glucose (IRR: 1.71 [95%CI: 1.29-2.28]) and physical inactivity (IRR: 1.46 [95%CI: 1.28-1.66]) were also independently associated with increased risk of NAFLD. In lean individuals, AD, elevated blood glucose and elevated BP were significantly associated with NAFLD although for elevated blood glucose, statistical significance was lost after adjusting for possible confounders. Physical inactivity and elevations in HsCRP were not associated with the risk of NAFLD in lean individuals only. Among lean (and non-lean) individuals, there was an independent association between progressively increasing waist circumference and NAFLD.ConclusionCardiometabolic risk factors are independently associated with NAFLD. However, there are significant differences in the metabolic risk predictors of NAFLD between lean and non-lean individuals. Personalized cardiovascular disease risk stratification and appropriate preventive measures should be considered in both lean and non-lean individuals to prevent the development of NAFLD