Helma Pinchemel Cotrim

Nonalcoholic steatohepatitis and hepatocellular carcinoma: natural history?

onstrated that the gastric mucous cells gain entry into the blood stream after gastric biopsy by using the glycosyltransferase,a4GnT as a cell-specific marker for gastric gland mucous cells. This fact, in turn, strongly suggests that gastric cancer cells could also enter the bloodstream after biopsy of the gastric cancer. Although the presence of circulating gastric cancer cells in peripheral blood do not necessarily lead to the (micro)metastasis of cancer cells, the results of our present study warn that the biopsy of gastric cancer tissues should be kept enough to a minimum for pathological examinations of the gastric mucosa.

Effects of light-to-moderate alcohol consumption on steatosis and steatohepatitis in severely obese patients.

Objectives The effect of light-to-moderate alcohol consumption (LMAC) in nonalcoholic fatty liver disease (NAFLD) remains a controversial subject. The aim of this study was to evaluate the relationship between LMAC and the severity of NAFLD in morbidly obese patients. Methods We studied 132 patients undergoing liver biopsy during bariatric surgery. The patients were divided into three groups: G1: alcohol intake greater than 20 g/day and less than 40 g/day; G2: alcohol intake less than 20 g/day; G3: no alcohol intake. Insulin resistance was defined by the Homeostasis Model Assessment (>3). NAFLD was classified according to the Matteoni types: type I: steatosis alone; type II: steatosis with inflammation; types III–IV: steatosis with ballooning and/or fibrosis. Results The mean age was 37.3±11 years. Sixty-three percent were females and body mass index was 43.9±5.6 kg/m2. G1, G2, and G3 included 19, 56, and 57 patients, respectively. Histological diagnoses classified by levels of alcohol were: G1: 10.5% normal liver, 89.5% type III or IV; G2: 10.7% normal liver, 1.8% type I or II, and 87.5% grade III or IV; G3: 10.5% normal liver, 3.5% type I or II, and 86% type III or IV (one had cirrhosis). The presence of IR was similar in moderate and no alcohol consumption (81.3 and 78.7%) but significantly less in the light consumption group (54%, P<0.05). Conclusion The results suggest that LMAC may have a protection effect against IR in severely obese patients. However, it had no impact on the severity of activity and stage of liver disease.

Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis

Mitochondrial dysfunction is an important element in the pathogenesis of nonalcoholic steatohepatitis (NASH). Intramitochondrial crystals (IMCs) are a well‐documented morphological abnormality seen on transmission electron microscopy in this disease. It has been suggested that IMCs consist of phospholipids, but their exact composition remain uncertain many years after their discovery. Micellar phase transitions of phospholipid bilayers is a well‐known but little‐studied phenomenon in living systems. Its presence in the mitochondria of NASH would offer significant insight into the disease with possible therapeutic implications. We postulated that intramitochondrial disturbances in NASH are sufficient to produce such transitions and that their detection in fresh biopsies would therefore be a dynamic process. To test this, we performed a blinded, prospective analysis of fresh liver biopsy samples immediately fixed under different conditions. Quantitative transmission electron microscopy morphometry, performed by systematically counting total mitochondria and IMCs within areas of uniform dimension, showed a stepwise decline in IMCs with cooler fixation temperature in each subject studied. Randomization testing (Monte Carlo resampling) confirmed that the detection of IMCs was strongly dependent on fixation temperature (P < 0.0001). Conclusion: These results indicate that the intramitochondrial crystals characteristic of NASH are highly dynamic and unstable structures. The findings offer the strongest support yet for their origin in micellar phase transitions. We speculate that such transitions result from microenvironmental changes within the mitochondria and carry therapeutic implications, especially in regard to dietary manipulations of mitochondrial lipid composition. (HEPATOLOGY 2009.)

Preoperative upper gastrointestinal endoscopy in obese patients undergoing bariatric surgery: is it necessary?

BACKGROUND Obesity has been shown to be an important risk factor for several gastrointestinal diseases. However, the indication for preoperative upper gastrointestinal endoscopy (UGE) for all patients before bariatric surgery is controversial. The aim of the present study was to evaluate the spectrum of gastrointestinal diseases detected during preoperative UGE in patients undergoing bariatric surgery and the relevance of this procedure. METHODS A series of severely obese patients, who had undergone UGE before Roux-en-Y gastric bypass from October 2004 to May 2005 were consecutively enrolled in this study. The demographic and clinical data and endoscopic diagnoses were evaluated. Gastric biopsies were performed in elective patients according to the endoscopic findings. RESULTS The study included 162 patients, 69.8% of whom were women. The mean age was 36.7 +/- 10.8 years. Abnormal findings were observed in 77.2% of patients. Esophagitis was present in 38.9%, gastritis in 51.2% (erosive gastritis in 49.3% and nonerosive gastritis in 50.7%), gastric ulcers in 1.9%, hiatal hernia, in 8.6%, gastric polyp in .6%, and duodenitis in 6.8% of patients. No patient had esophageal or gastric varices. Helicobacter pylori infection was investigated in 96 patients and was detected in 37.5%. Gastric biopsies were performed in 36 patients, with chronic inflammation found in 72.2%, inflammatory activity in 30.6%, and intestinal metaplasia in 11.1%. Glandular atrophy was not found in any patient. CONCLUSION The results of our study have shown that the spectrum of gastrointestinal diseases observed in severely obese patients who underwent bariatric surgery is broad. Although this issue remains highly controversial, these findings suggest that systematic preoperative UGE and H. pylori testing should be performed in all patients scheduled to undergo bariatric surgery.

Non-alcoholic fatty liver disease and insulin resistance: importance of risk factors and histological spectrum.

Background Non-alcoholic fatty liver disease (NAFLD) has been associated with several metabolic conditions (MC) and secondary causes, but the relationship between insulin resistance (IR) and the underlying aetiology of NAFLD has not been extensively explored. Objective To determine the frequency of IR among NAFLD patients and to describe IR according to risk factors and histological findings of the disease. Methodology A case-series study of 64 patients with clinical and histological diagnosis of NAFLD. IR was calculated by homeostasis model assessment (HOMA) and IR was considered when HOMA ⩾3. Histological grades of NAFLD were: stage 1, steatosis isolated; stage 2, steatosis and inflammation; stage 3, steatosis and ballooning degeneration; stage 4, steatosis and fibrosis and/or Mallory bodies. Fibrosis was graded 0–4 (cirrhosis). Results IR was found in 21 (33%) patients. Among those with IR, 16 patients (76%) had associated MC and five patients (24%) had exposure to petrochemicals. The mean value of HOMA varied from 3.5 in NAFLD associated with MC to 1.6 in patients with exposure to petrochemicals (P<0.03). Waist circumference was the metabolic factor most strongly associated with IR (P<0.005). Steatohepatitis (NASH) was observed in 54 (84.3%) cases. The HOMA mean value was significantly higher in patients with advanced fibrosis. Conclusions IR occurred in 33% of the NAFLD patients, being more frequent among those with MC than among those with exposure to petrochemicals. The presence of IR in cases with advanced fibrosis suggests that it may influence the prognosis of NAFLD.

Clinical and histopathological features of NASH in workers exposed to chemicals with or without associated metabolic conditions

Background/Aims: Non‐alcoholic steatohepatitis (NASH) has been associated with exposure to chemicals among workers from an industrial complex in Brazil. We investigated the NASH profile of these individuals associated or not with metabolic conditions.

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 800 mg 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.

Anabolic-androgenic steroids: a possible new risk factor of toxicant-associated fatty liver disease.

Background: Industrial toxin and drugs have been associated with non‐alcoholic fatty liver disease (NAFLD); in these cases, the disease has been termed toxicant‐associated steatohepatitis (TASH).

HCV infection in northeastern Brazil: unexpected high prevalence of genotype 3a and absence of African genotypes

The genomic diversity of HCV embraces 6 genotypes and at least 52 subtypes with clinical and epidemiological correlations. There is a paucity of studies assessing HCV genotypes and biomolecular epidemiology in Brazil. We studied genotype distribution and epidemiological aspects in 232 HCV carriers, 133 (57.9%) males and 99 (42.1%) females, followed in the liver disease referral unit in Salvador, BA, northeastern Brazil. All of them were anti-HCV positive by 3rd generation ELISA assay, and HCV-RNA positive by RT-PCR. Genotyping was performed by INNOLIPA. Assessment of risk factors for HCV infection showed that 93 (40%) had past blood transfusion, 14 (6%) intravenous drug use, 19 (8%) inhalation of cocaine, 28 (12%) tattooing, 15 (7%) were health care workers, 5 (2%) had reused disposable syringes, 5 (2%) had multiple risk factors and in 53 (23%) no risk factor was determined. Genotype 1a was observed in 75 (32%), 1b in 72 (31%), 3a in 61 (26%), 2ab in 14 (6%); 5 (2.5%) had mixed genotypes and 5 (2.5%) were undetermined. Patients with genotype 1 had a higher mean age (P < 0.05) and no particular risk factors were associated with a specific genotype. Genotype 1 largely predominates in northeast Brazil followed by genotype 3 which, in this population, does not seem to be related to intravenous drug abuse, in contrast to some European studies. Although 80% of the Salvador population comprises African-Brazilians, no African genotype was identified, which may mean that HCV was introduced into this region via European immigration. This study demonstrated some peculiarities of HCV epidemiology in Brazil and strongly suggests that HCV introduction to this region was probably related to European immigration.

Alterações hepáticas em trabalhadores de uma refinaria de petróleo e em uma população de referência no Estado da Bahia, Brasil

OBJETIVO: Determinar a prevalencia de alteracoes nas enzimas hepaticas de trabalhadores de uma refinaria de petroleo localizada no Estado da Bahia em comparacao a uma populacao de referencia nao ocupacionalmente exposta a produtos quimicos, e descrever os fatores associados a variacao nessa prevalencia. METODO: Foram avaliados os trabalhadores da refinaria e os funcionarios do escritorio da gerencia administrativa da empresa, situada em Salvador, capital do Estado da Bahia. Estudaram-se amostras de sangue de 692 trabalhadores da refinaria e de 377 trabalhadores da populacao de referencia. Classificaram-se como casos de alteracoes hepaticas individuos que apresentaram valores acima dos padroes de referencia simultaneamente para gama-glutamiltransferase (GGT) (>50 U/L para o sexo masculino e >32 U/L para o sexo feminino) e alanina aminotrans- ferase (ALT) (>50 U/L). Foram coletadas informacoes sobre idade, sexo, peso, altura, tempo de servico, uso de alcool, habito de fumar, exercicio fisico, exposicao ocupacional a produtos quimicos, uso de equipamento de protecao individual e antecedentes medicos de hepatite, ictericia e obesidade. RESULTADOS: A prevalencia de alteracoes hepaticas na refinaria foi de 15,3% (IC95%: 12,5 a 18,1), contra 3,8% (IC95%: 1,8 a 5,8) na populacao de referencia. A analise de regressao logistica multipla estimou que os trabalhadores da refinaria apresentavam uma prevalencia de alteracoes hepaticas 3,56 vezes maior (IC95%: 1,99 a 6,38) do que a prevalencia observada na populacao de referencia, independentemente de outras covariaveis relevantes, como obesidade, pratica de exercicios fisicos, fumo e bebida alcoolica. CONCLUSOES: Os resultados sugerem que a exposicao ocupacional desempenha um papel importante na determinacao das alteracoes hepaticas nos trabalhadores dessa refinaria de petroleo.