Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis.

Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.

Transjugular intrahepatic portosystemic shunt with transhepatic portal vein puncture guided by ultrasound: a technical alternative.

OBJECTIVE: Evaluation of an alternative technique to perform transjugular intrahepatic portosystemic shunt (TIPS), using abdominal ultrasound to guide portal puncture. METHODS: Retrospective analysis of TIPS performed from January 2014 to December 2018 in an interventional radiology service. TIPS were performed according to the classic technique, except at the moment of portal branch puncture, when abdominal ultrasound was used to guide it, visualized its path within the parenchyma in real-time. Qualitative and quantitative variables were analyzed considering a 95% confidence interval and application of the Student's t-test with a significance level of P < 0.05. RESULTS: Forty-one TIPS were performed. The technical success rate of ultrasound guidance in portal puncture was 100.0%. After its performance, a reduction in the portosystemic pressure gradient was observed, with an initial gradient average of 18.8 mmHg (12-25 ± 3.6 mmHg) and a final gradient of 9.2 mmHg (5-14 ± 2.4 mmHg). The mean values for the TIPS execution time, fluoroscopy time and the radiation dose, verified through the dose area product, were 65.2 ± 46.7 min, 25 ± 14.1 min and 85.6 ± 70 Gy cm2, respectively. There were no complications related to the inadvertent puncture of nontarget structures or deaths due to complications resulting from TIPS. CONCLUSION: The results demonstrate that the portal transhepatic puncture guided by the abdominal ultrasound is an effective and safe procedure and results in time of execution, time of fluoroscopy and radiation dose below the current reference values of the conventional procedure.

Albumin in the management of hepatic encephalopathy: A systematic review and meta-analysis.

Introduction and objectives It has been suggested that albumin administration could alter the natural history of cirrhosis, and also, that long-term treatment with albumin might be associated with improvement in survival, control of ascites, reduction in the incidence bacterial infections, renal dysfunction, hepatic encephalopathy (HE) and hyponatremia, as well as reduction in length of hospitalization in patients with cirrhosis and ascites. The objective of the present study is to evaluate the role of albumin in the management of HE. Materiales and methods:: This is a systematic review of randomized controlled trials that evaluated the use of albumin in adult patients with cirrhosis and HE. The search for eligible studies was performed in MEDLINE, EMBASE, and Cochrane CENTRAL databases until June 2020. The outcomes of interest were the complete reversal of HE and mortality. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. Results: This systematic review was registered at the PROSPERO platform (CRD42020194181). The search strategy retrieved 1,118 articles. After reviewing titles and abstracts, 24 studies were considered potentially eligible, but 22 were excluded after full-text analysis. Finally, 2 studies were included. In the meta-analysis, albumin was associated to significant lower risks of persistent HE (risk ratio - RR = 0.60; 95% confidence interval - CI = 0.38-0.95, p = 0.03) and mortality (RR = 0.54; 95% CI = 0.33-0.90, p = 0.02). Conclusion: Albumin administration improves HE and reduces mortality in patients with cirrhosis and HE.

The prognostic impact of different stages of acute kidney injury in patients with decompensated cirrhosis: a prospective cohort study.

AIM: To assess the impact of the different stages of acute kidney injury (AKI) on the prognosis of patients hospitalized with decompensated cirrhosis. METHODS: This was a prospective cohort study of consecutive patients admitted in two tertiary hospitals in southern Brazil. Participants were considered eligible if they were admitted for acute decompensation of cirrhosis. The main exposure factor was the onset of AKI. AKI stages were defined according the European recommendations. The outcomes evaluated were survival time and death rates at 28 and 90 days from hospital admission. A χ2 test was used to compare mortality between groups. Kaplan-Meier survival analyses were undertaken assessing time to event as days from AKI diagnosis to death or liver transplant. RESULTS: Two hundred and five patients were included in the study, and 121 met the criteria for AKI. Patients with AKI 1b, AKI 2 and AKI 3 had higher 90-day mortality than patients without AKI (P = 0.008, P < 0.001 and P < 0.001, respectively). However, there was no difference in 90-day mortality when patients with AKI 1a were compared with those without AKI (P = 0.742). The mean survival of patients without AKI was higher than that of patients with AKI 1b (591.4 and 305.4 days, respectively, P = 0.015), while there was no significant difference between the mean survival of patients without AKI and that of patients with AKI 1a (591.4 and 373.6 days, respectively, P = 0.198). CONCLUSION: Only AKI ≥1b seems to substantially impact mortality of patients hospitalized for acute decompensation of cirrhosis.

Treatment of hepatitis B virus infection in chronic infection with HBeAg-positive adult patients (immunotolerant patients): a systematic review.

Recently, a controversial approach suggesting the early treatment of chronic infection with hepatitis B "e" antigen-positive patients with hepatitis B virus (HBV) infection, has been proposed. The objective of this study is to systematically review medical literature regarding treatment of HBV infection in adult chronic infection with HBeAg-positive patients. A systematic review was performed according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Original studies that evaluated the effect of antivirals in adult chronic infection with HBeAg-positive patients were included. The outcomes of interest were viral load suppression, the loss/seroconversion of HBeAg, the loss/seroconversion of hepatitis B surface antigen, and the development of cirrhosis or hepatocellular carcinoma. The search for eligible studies was performed in Excerpta Medica dataBASE, PubMed and Cochrane databases until January 2020, without language or date restriction. The risk of bias was evaluated using the Newcastle-Ottawa Scale for observational studies and the Revised Cochrane Risk-of-Bias Tool for randomized controlled trials. Two hundred ninety-six articles were retrieved. After analyzing titles and abstracts, 287 articles were excluded and nine were considered potentially eligible. From these, five were excluded after full-text analysis. Finally, four articles were included. Only two were randomized controlled trials. All studies were carried out in Asian patients. Results were variable with regard to viral load, negativation/seroconversion of HBeAg and HBsAg. One study demonstrated that treated patients developed cirrhosis or hepatocellular carcinoma less frequently than untreated individuals. Overall, the studies were of poor quality. In conclusion, the present systematic review demonstrated that, at present, there is not enough evidence to recommend treating this population of patients.

Role of zinc supplementation in the management of chronic liver diseases: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Zinc deficiency has been associated with poor prognosis in chronic liver disease. This systematic review and meta-analysis aimed to evaluate the role of zinc supplementation in the management of chronic liver diseases. MATERIALS AND METHODS: We searched MEDLINE, LILACS, EMBASE, and Cochrane CENTRAL databases from inception to August 2018. We included randomized controlled trials evaluating adult patients with chronic liver disease of any etiology receiving zinc supplementation. Studies with other designs or evaluating chronic conditions other than liver disease were excluded. Two reviewers independently screened and extracted data from eligible studies. Study quality was assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomized studies. RESULTS: Of 1315 studies screened, 13 were included. Six assessed chronic hepatitis C treatment, with a relative risk of 0.83 indicating no protective effect of zinc supplementation on the improvement of sustained virological response. Three evaluated response to hepatic encephalopathy treatment, with a relative risk of 0.66 indicating a favorable effect of zinc supplementation on clinical improvement of this condition. Of four studies evaluating the management of cirrhosis, two analyzed the effect of zinc supplementation on serum albumin levels, with no statistical difference between zinc and placebo groups. CONCLUSIONS: Clinical trials assessing zinc supplementation in liver diseases do not show benefits in terms of clinical improvement or disease halting. There are possible benefits of zinc supplementation on hepatic encephalopathy, however, this is based on limited evidence. This research question is still open for evaluation in larger, well-designed, clinical trials.

Evaluation of response to hepatitis B virus vaccine in adults with human immunodeficiency virus.

INTRODUCTION AND AIM: Viral hepatitis is a serious public health problem. The risk of progression to chronic hepatitis in hepatitis B virus (HBV) infection occurs in 5-10% of adults and is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Individuals infected with human immunodeficiency virus (HIV) may have coinfection with HBV. The existence of unvaccinated groups represents a significant risk not only individually but also at the community level. The aim of this study was to evaluate HBV vaccine response in adults with HIV infection. MATERIALS AND METHODS: A retrospective, descriptive study of the cross-sectional type was carried out in an outpatient HIV referral center in southern Brazil. All medical records of adult HIV patients seen during January 2006 to December 2015 were selected. In statistical analysis, a significance level of 5% was used. RESULTS: Of the 201 patients evaluated with a complete vaccination scheme, 55.72% were males, with a mean age of 43.86±12.68 years. Vaccine response occurred in 80.10% (161/201) of the patients, and it did not correlate with age, CD4+ cell count or viral load. CONCLUSION: HBV vaccine response in a HIV population was satisfactory, highlighting the importance of vaccination for prevention, cost reduction and better prognosis in preventing HBV/HIV coinfection.

Acute-on-chronic liver failure: A comparison of three different diagnostic criteria.

INTRODUCTION AND AIM: Different criteria are applied for the diagnosis of acute-on-chronic liver failure (ACLF). Our aim was to compare the performance of different ACLF diagnostic criteria for predicting mortality. MATERIALS AND METHODS: This was a prospective cohort study of adult cirrhotic patients admitted to a tertiary hospital for acute decompensation (AD) of cirrhosis. The evaluated outcome was mortality at 28 and 90 days, according to the different ACLF diagnostic criteria: Chronic Liver Failure Consortium (CLIF-C), Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC) and North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Prognostic performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 146 patients were included. 43 (29.5%) with ACLF according to CLIF-C definition, 14 (9.6%) with ACLF by AARC definition, and 6 (4.1%) by NACSELD definition. According to Kaplan-Meier survival analyses median survival of patients with ACLF by CLIF-C definition was 27.0 days, median survival of patients with ACLF by AARC definition was 27.0 days, and median survival of patients with ACLF by NACSELD definition was 4.0 days. The areas under the ROC curves for performance evaluation in predicting mortality at 28 days for CLIF-C, AARC and NACSELD criteria were, respectively, 0.710, 0.560 and 0.561 (p=0.002). Regarding 90-day mortality, the areas under the ROC curves were 0.760, 0.554 and 0.555 respectively (p<0.001). CONCLUSION: ACLF definition proposed by CLIF-C had better performance in predicting mortality at 28 and 90 days when compared to criteria proposed by AARC and NACSELD.

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION AND AIM: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.

Sarcopenia and non-alcoholic fatty liver disease: Is there a relationship? A systematic review.

AIM: To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) in adult patients with sarcopenia. METHODS: Randomized clinical trials, cross-sectional or cohort studies including adult patients (over 18 years) with sarcopenia were selected. The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients. In the screening process, 44 full-text articles were included in the review and 41 studies were excluded. RESULTS: Three cross-sectional studies were included. The authors attempted to perform a systematic review, but due to the differences between the studies, a qualitative synthesis was provided. The diagnosis of NAFLD was made by non-invasive methods (image methods or any surrogate markers) in all three evaluated studies. All the studies suggested that there was an independent association between sarcopenia and NAFLD. CONCLUSION: Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis.

Treatment of hepatocellular carcinoma using transarterial chemoembolization: a real-life, single-centre study from Southern Brazil.

OBJECTIVE: The main aim of this study was to evaluate the real-life survival rates of patients with intermediate-stage hepatocellular carcinoma treated with transarterial chemoembolization. METHODS: A retrospective cohort study involving 95 patients was conducted and the studied variables were analysed according to survival. Treatment response was determined using the Modified Response Evaluation Criteria in Solid Tumors assessment. The Kaplan-Meier method and Cox regression were used to analyse survival. RESULTS: Most (72.6%) patients were male, with a mean age of 64.8±9.7 years and mean Model for End-Stage Liver Disease score of 10.4±3.0. The median α-fetoprotein (AFP) level was 29.3 ng/ml. Complications were observed in 31.6% of the patients. A target response assessment revealed that 35.8% of patients exhibited complete response, 22.1% a partial response, 27.4% stable disease and 14.7% progressive disease. According to overall response rates, 63.2% exhibited progressive disease. Mean survival time was 32 months. The 1-, 2-, 3- and 5-year survival rates were 80, 59, 44 and 29%, respectively. In the multivariate model adjusted for overall response rates, only AFP level more than or equal to 100 ng/ml (hazard ratio=2.35, 95% confidence interval: 1.06-5.18, P=0.035) was associated with death. CONCLUSION: Transarterial chemoembolization is an effective therapy; however, AFP levels more than or equal to 100 ng/ml are associated with poorer prognosis.

Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients.

The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH) and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4%) and NASH in 176 (70.4%) cases. The diagnosis of cirrhosis was established in four cases (1.6%) and fibrosis in 108 (43.2%). Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN); glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease.

Burden of liver disease in Brazil.

BACKGROUND & AIMS: The burden of liver diseases in the Brazilian population is still unknown. To assess the impact of liver diseases on hospital admissions and mortality within the framework of the Brazilian Unified Health System. METHODS: An analytical ecological observational study was carried out. Secondary data on hospital admissions and deaths because of liver disease were collected from the Unified Health System Information Technology Department (DATASUS) database, between 2001 and 2010. All liver diseases included in the International Classification of Diseases (ICD-10) were reviewed. RESULTS: Liver diseases were the eighth leading cause of death in Brazil. The prevalence of hospital admission because of liver disease during the period of analysis was 0.72% (853 571 hospitalizations), and the mortality rate was 3.34% (308 290 deaths). The mean age at hospital admission and death because of liver disease was 48.05 and 58.10 years respectively. Both hospitalization and death because of liver disease were more common among men, and followed an upward trend over the years. Cirrhosis was the main cause of hospital admissions and death by liver disease in Brazil. The South region of the country had the highest hospital admission rates because of liver disease in Brazil, whereas the Southeast region had the highest mortality rate. CONCLUSION: This study provides evidence of the relevance of liver diseases within the framework of the Brazilian Unified Health System, and shows that the burden of these diseases is not only significant but progressive, at least in terms of hospital admissions and mortality rate.

Treatment of hepatitis C with peginterferon and ribavirin in a public health program.

BACKGROUND/AIMS: In hepatitis C treatment, literature is limited with regard to independent studies developed outside the context of clinical assays. To evaluate the sustained virological response to the treatment of patients with chronic hepatitis C genotype 1 in a public program in the south of Brazil. METHODOLOGY: It is a mixed cohort, the data of all patients with chronic hepatitis C treated with peginterferon associated with ribavirin for 48 weeks were collected. If there was no early virological response on week 12 the treatment was discontinued. The significance level adopted in the statistical analysis was micro = 0.05. RESULTS: The cohort was comprised of 323 individuals. The treatment was completed in 215 (66.6%) patients. With the intention to treat analysis, the sustained virological response was obtained in 114 (35.3%) patients. The factors predictive of the response were lower age (below 40 years) and minor fibrosis (< F3 according METAVIR score), as well as viral load less than 600,000 IU/ml and the absence of hepatitis C virus viremia on 12th week of treatment. CONCLUSION: The sustained virological response in patients with chronic hepatitis C genotype 1 treated with peginterferon and ribavirin in a public health system did not reproduce the results obtained in the major clinical trials.

[Bacterial infection in cirrhotic patient]. / Infecção bacteriana no paciente cirrótico.

BACKGROUND: Bacterial infections at admission or during hospitalization are frequent complication of cirrhosis that occurs in about 30% of the cases. Furthermore they are responsible for 25% of deaths in this population. AIM: Evaluate the prevalence of bacterial infections in cirrhotic patients at a general hospital and determine its correlation with alcoholic etiology of liver disease; degree of hepatic dysfunction and upper gastrointestinal bleeding. PATIENTS/METHODS: Five hundred and forty one admissions were retrospectively evaluated in 426 cirrhotic patients at years 1992 to 2000. The mean age was 50.5 years (15-95), being 71.2% male. The alcoholic etiology of cirrhosis was 35.4%. The main outcome considered was discharge or death during admission. RESULTS: One hundred and thirty five episodes of bacterial infections (25%) were diagnosed. The most frequent are urinary tract infection (31.1%), spontaneous bacterial peritonitis (25.9%) and pneumonia (25.2%). The association between urinary tract infection and pneumonia occurred in 3.7% and erysipelas or cellulites in 11.1%. Bacteremia occurred in 2.9%. There was a correlation between bacterial infection and alcoholic etiology of liver disease, hepatic dysfunction and upper gastrointestinal bleeding. The mortality was higher in the infected patients (8.9%) and in those with a poor hepatic function. CONCLUSIONS: Bacterial infections are common complications in cirrhotic patients and are correlated with alcoholic etiology, Child Pugh classification and upper gastrointestinal bleeding. Furthermore, bacterial infections are correlated with poor prognosis.

The influence of endoscopic variceal ligation on the portal pressure gradient in cirrhotics.

BACKGROUND/AIMS: After variceal eradication by endoscopic ligation, fundal varices and worsening of portal hypertensive gastropathy can occur. The aim of this study is to verify the impact of the eradication of esophageal varices by endoscopic ligation on the portal pressure gradient, worsening of portal hypertensive gastropathy and development of fundal varices. METHODOLOGY: Twenty-two (15M/7F, mean age: 54.5 years) cirrhotics with previous variceal bleeding were submitted to measurement of hepatic venous pressure gradient before and after variceal eradication by endoscopic ligation. RESULTS: The mean hepatic venous pressure gradient in the first measurement was 14.1 mmHg and after eradication, 13.5 mmHg (p = 0.403). After eradication, 12 patients experienced a reduction in portal pressure and 10, an elevation. Three patients developed fundal varices. Their mean gradient before treatment was 22 mmHg and 18.8 mmHg after therapy (p = 0.368). The gastropathy worsened in 9 patients (mean gradient before therapy of 15.2 mmHg; and 16.1 mmHg after treatment) (p = 0.303). The initial pressure gradient of these patients was not different from the other 13 cases (p = 0.463). CONCLUSIONS: The esophageal variceal eradication by endoscopic band ligation does not alter the hepatic venous pressure gradient. There is no significant variation in the portal pressure of patients in whom there was a worsening of portal hypertensive gastropathy or fundal varices development.