Schistosomal portal hypertension: Randomized trial comparing endoscopic therapy alone or preceded by esophagogastric devascularization and splenectomy.

UNLABELLED:  Background. Upper gastrointestinal bleeding is a major cause of morbidity and mortality in patients with portal hypertension secondary to schistosomiasis mansoni. AIM: To evaluate the efficacy of combined surgery and sclerotherapy versus endoscopic treatment alone in the prophylaxis of esophageal variceal rebleeding due to portal hypertension in schistosomiasis. MATERIAL AND METHODS: During a two-years period consecutive patients with schistosomiasis and a recent bleeding history were evaluated for prospective randomization. Absolute exclusion criteria were alcoholism or other liver diseases, whereas platelet count < 50,000/mm3, INR > 1.5 or presence of gastric varices were relative exclusion criteria. By random allocation 25 (group A) have received endoscopic sclerotherapy for esophageal varices alone and 22 (group B) combined treatment: esophagogastric devascularization with splenectomy followed by sclerotherapy. Interim analysis at 24 months has shown significant statistical differences between the groups and the randomization was halted. RESULTS: Mean age was 38.9 ± 15.4 years and 58.46% were male. Mean follow-up was 38.6 ± 20.1 months. Endoscopic comparison of the size of esophageal varices before and after treatment did not show significant differences among the two groups. Treatment efficacy was assessed by the rate of recurrent esophageal variceal bleeding, that was more common in group A- 9/25 patients (36.0%) vs. 2/22 (9.0%) in group B (p = 0.029). Other complications were odynophagia, dysphagia and esophageal ulcer in group A and ascites and portal vein thrombosis in the surgical group. CONCLUSION: In portal hypertension due to schistosomiasis, combined surgical and endoscopic treatment was more effective for the prevention of recurrent esophageal variceal bleeding.

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.

The impact of bacterial infections on survival of patients with decompensated cirrhosis.

INTRODUCTION. Bacterial infection in cirrhotic patients is a severe complication that requires early recognition and specific therapeutic care. MATERIAL AND METHODS. In this review the various aspects of diagnosis and management of infections that may impact survival in cirrhosis are analyzed. RESULTS. Active search for infections allows early detection and its treatment with suitable antibiotics has reduced mortality rates in spontaneous bacterial peritonitis, the main infection in patients with decompensated cirrhosis. Other common infections, such as bacteremia and septicemia or urinary tract, lung, skin and soft tissue infections must be thoroughly investigated so that antibiotic treatment can be started early. As intestinal bacterial translocation is one of the most important mechanisms for development of bacterial infections, selective intestinal decontamination is able to prevent these infections in populations at risk. After the first episode of spontaneous bacterial peritonitis, poorly absorbed oral antibiotics, such as quinolones, must be started and continued. Moreover, when there is upper gastrointestinal bleeding, infection prevention should be based on oral administration of quinolones or intravenous administration of cephalosporins, both for seven days, to avoid morbidity and early lethality. With the advent of resistance to commonly used antibiotics and recent reports of multiresistant bacteria, there is a need for stricter control when administering antibiotics to cirrhotic patients. CONCLUSION. Existing knowledge of therapy and prophylaxis for bacterial infections in cirrhotic patients, which undoubtedly improve survival, should be disseminated and applied in clinical practice for the benefit of the population at large.

Usefulness of liver biopsy in chronic hepatitis C.

Major requirements for performance of liver biopsy (LB) are the benefits for the patient and the impossibility of having the same information by less invasive procedures. In the last two decades physicians have faced the difficult task of convincing a patient positive for hepatitis C, with minimal clinical or laboratory alterations to be submitted to LB in order to evaluate the status of the disease for therapeutic management. The characteristics of the needle used for percutaneous LB interferes with the accuracy of diagnosis. In chronic hepatitis C (CHC), validity is achieved with liver fragments about 25 mm in length containing more than 10 portal tracts. Morbidity due to LB is mainly related to bleeding but death is very rare. Severe complications are also uncommon, increasing with number of passes and decreasing with experience of operator and ultrasound guidance. Although CHC is a diffuse disease, the various areas of the liver may not be equally affected and sampling errors are possible. Another potential limitation of LB is the discordance between pathologists in its interpretation. To replace LB, many panels of surrogate markers have been described, aiming to identify extent of fibrosis and inflammation. All of them have used LB as their gold standard. Liver biopsy continues to be the most reliable method to evaluate the possibility of therapy for CHC. Universal treatment of all patients with diagnosis of CHC would be ideal. But, there are mainly three drawbacks. Overall efficacy is as low as 50%, side effects are common and may be severe and treatment is prolonged and expensive. The acceptability of the biopsy by the patient is highly dependent on the physicians conviction of its usefulness.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B.

Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified. Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment. The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc). Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Use of AST platelet ratio index (APRI Score) as an alternative to liver biopsy for treatment indication in chronic hepatitis C.

Chronic hepatitis C (CHC) is one of the most important causes of chronic liver disease in the world, potentially resulting in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Liver biopsy is currently performed before therapy indication. Although, it is the golden standard there are many reasons to avoid or delay the procedure. APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C (CHC). The rationale of this study was to observe the accuracy of APRI Score in comparison to liver biopsy in 400 patients divided into two groups of 200 carriers (Validation and Experimental groups respectively) selected at random or according to liver fibrosis staging (METAVIR). The ROC curves showed a concordance among these two methods of 92% and 88.5% when 1.05 was the cut off (F3 and F4), and 87% and 83%, on 0.75 cut offs (F2-F4). The discordance in advanced fibrosis staging (F3 and F4) was only 16 (8%) and 22 (11%) out of 200 patients in the experimental and validation groups, respectively. In 26 (13%) out of 200 patients in the experimental group and 34 (17%) out of 200 patients in the validation group, there was discordance between APRI Score and liver biopsy in moderate and advanced fibrosis (F2-F4). In conclusion APRI is a serological marker that has satisfactory sensitivity and specificity together with a high predictive value and it can be useful either in the absence of a biopsy or to reduce the frequency with which biopsies need to be carried out to monitor the evolution of chronic hepatitis C and the right moment for treatment indication.

Liver transplantation and quality of life: relevance of a specific liver disease questionnaire.

AIM: A positive effect of liver transplantation on health-related quality of life (HRQOL) has been well documented in previous studies using generic instruments. Our aim was to re-evaluate different aspects of HRQOL before and after liver transplantation with a relatively new questionnaire the 'liver disease quality of life' (LDQOL). METHODS: The LDQOL and the Short Form 36 (SF-36) questionnaires were applied to ambulatory patients, either in the transplant list (n=65) or after 6 months to 5 years of liver transplant (n=61). The aetiology of cirrhosis, comorbidities, model for end-stage liver disease (MELD) Child-Pugh scores and recurrence of liver disease after liver transplantation were analysed using the Mann-Whitney and Kruskall-Wallis tests. RESULTS: In patients awaiting liver transplantation, MELD scores > or =15 and Child-Pugh class C showed statistically significant worse HRQOL, using both the SF-36 and the LDQOL questionnaires. HRQOL in pretransplant patients was found to be significantly worse in those with cirrhosis owing to hepatitis C (n=30) when compared with other aetiologies (n=35) in 2/7 domains of the SF-36 and in 7/12 domains of the LDQOL. Significant deterioration of HRQOL after recurrence of hepatitis C post-transplant was detected with the LDQOL questionnaire although not demonstrated with the SF-36. The statistically significant differences were in the LDQOL domains: symptoms of liver disease, concentration, memory and health distress. CONCLUSIONS: The LDQOL, a specific instrument for measuring HRQOL, has shown a greater accuracy in relation to liver symptoms and could demonstrate, with better reliability, impairments before and after liver transplantation.

RECOMMENDATIONS OF THE BRAZILIAN SOCIETY OF HEPATOLOGY FOR THE MANAGEMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS.

Acute kidney injury is a common complication of cirrhosis, occurring in up to 20% of patients hospitalized with cirrhosis. This field is rapidly changing, with significant advances in classification, biomarkers and therapy over the last few years. On the behalf of the Brazilian Society of Hepatology, a panel of experts in Hepatology and Nephrology reviewed published evidence to integrate findings and develop the recommendations presented in this manuscript.

Barriers to care of chronic hepatitis patients in Latin America.

Delay in diagnosis of chronic hepatitis due to HCV or HBV is mainly caused by lack of information about these prevalent and life-threatening disorders. Diagnostic tests are either not easily available or not requested by primary care physicians. When cases positive for hepatitis-B markers or anti-HCV are found, misleading guidance may be given to patients. Absence of symptoms associated with lack of information is another barrier to the care of chronic hepatitis patients. Management of these diseases is not simple, and treatment options and schedules are in rapid and continuous evolution. Surveillance of patients with chronic hepatitis before, during and after antiviral therapy is mandatory. For patients with no indication for therapy, identification of optimal follow-up frequency constitutes a problem, as does determination of the correct amount and type of diagnostic tests to be used. Another important barrier to care of patients with chronic hepatitis is the absence of an ideal drug, namely, one that is inexpensive, does not have collateral effects, and has very high percentages of cure or resolution. Access to therapy is uncertain, and the side effects of interferon frighten some patients and physicians. Lack of adherence to the medication, early interruption, and the need for other supportive therapies are frequent barriers to successful treatment.

Changes in histological criteria lead to different prevalences of nonalcoholic steatohepatitis in severe obesity.

The worldwide obesity epidemic contributes to the increasing incidence of a number of diseases, as nonalcoholic fatty-liver disease (NAFLD) and its most severe form, the nonalcoholic steatohepatitis (NASH). Data on the prevalence of NASH has varied from 18.5%(5) to 69%(43 )in obesity, an unacceptable wide range. The aim of our study was to evaluate how prevalence of NASH is influenced by the different diagnostic histological criteria. Consecutive assessment of 325 obese patients referred for bariatric surgery (BMI >or = 35 kg/m(2)), 146 of whose were submitted to histological analysis of the liver allowed the evaluation of the prevalence of NAFLD. Steatohepatitis was diagnosed histologically using 3 types of criteria: a) broad criteria, where steatosis was associated with at least 2 of the following parameters: any degree of lobular inflammatory infiltrate, hepatocellular ballooning and perisinusoidal/ perivenular fibrosis; b) restricted criteria, where the hepatocellular ballooning was of moderate or severe intensity; c) ultrarestricted criteria, which required perisinusoidal and/or perivenular fibrosis. NAFLD was present in 111 (76%) of the patients, and the prevalence of NASH was 25.3% when ultrarestricted criteria were used, 41.1% with restricted criteria and 55.5% with broad criteria. In conclusion, more accurate definition of the criteria for histological diagnosis of NASH should be required, so that further clinicopathological studies may define the long-term progression of the disease and evaluate therapeutic strategies.

VARICEAL BLEEDING: UPDATE OF RECOMMENDATIONS FROM THE BRAZILIAN ASSOCIATION OF HEPATOLOGY.

Since the publication of the Brazilian Association of Hepatology recommendations for the prevention and treatment of variceal bleeding in 2010, new evidence-based data were reported in the literature. This has changed our current management for portal hypertension. This review updates the previous recommendations. It takes the new prognostic staging of cirrhosis into account allowing tailored treatment for advanced fibrosis, compensated or decompensated cirrhosis. An organizing panel of five experts reviewed all recommendations according to available data, which were subsequently scrutinized by all members of the Brazilian Association of Hepatology using a web-based approach. The accepted recommendations are presented in this manuscript.

A new insight into the differences among non-cirrhotic and cirrhotic patients using the liver disease quality of life instrument (LDQOL).

Our aims were to validate the Brazilian Portuguese version of the Liver Disease Quality of Life Questionnaire instrument (LDQOL1.0) and evaluate this tool in non-cirrhotic patients. METHODS: The LDQOL1.0 consists of the SF-36 generic measure of health-related quality of life (HRQOL) and 12 disease-specific dimensions for patients with liver disease. The Brazilian Portuguese version instrument was administered to 103 patients with liver disease. Reliability was analyzed by studying the internal consistency of the individual disease- specific dimensions of the LDQOL, as well as by studying the test-retest reliability in a sub-group of 74 patients who completed the questionnaire on two occasions 1 to 2 weeks apart. Validity was analyzed by determining the instrument's ability to discriminate between groups of patients according to severity of the liver disease. RESULTS: Internal consistency in the disease- specific dimensions was good (CACs 0.66-0.94), as well as test-retest reliability in all dimensions (ICCs of 0.64-0.96) p<0.05. We found statistically significant differences in six domains when compensated cirrhotic patients, Child A, were compared with non-cirrhotic patients. We also found statistically significant differences when we compared cirrhotic patients evaluated assessed by Child-Pugh and Meld classifications. Patients with Child C and Meld>or=15 showed worse quality of life. Moderate ceiling and floor effects were found in some disease-specific dimensions. IN CONCLUSIONS: the Brazilian Portuguese version of the LDQOL 1.0 is very useful for measuring HRQOL in liver diseases.

Alcoholic intake predisposes to more interface hepatitis in chronic hepatitis C.

Progression of liver disease in chronic hepatitis C depends on several factors related to the host, virus and the environment which deserves further investigations. 120 candidates for blood donation with hepatitis C virus were divided into three groups according to alcohol intake: abstainers, light drinkers and heavy drinkers. Liver histopathology alterations, namely architectural staging, periportal and lobular inflammation as well as portal inflammatory infiltrate were graded from 0 to 4 and afterwards divided into light (0 to 2) and severe (3 to 4). There were more drinkers among men (83.5%) than among women (41.5%). Regarding the three groups, mild periportal inflammation was significantly related with abstainers and light drinkers groups whereas severe periportal inflammation was more predominant in heavy drinkers (p = 0.033). When we compared mild with severe histopathological alterations older age was significantly (p = 0.004) associated with severe fibrosis, periportal inflammation and portal inflammatory infiltrate. In relation to enzyme levels a significant difference in fibrosis and lobular activity was found for ALT, AST and GGT. Only AST was a marker of greater portal inflammatory infiltrate. Additionally, platelets were significantly lower in severe fibrosis and in periportal inflammation. Logistic regression analysis identified AST and platelets as independent predictors for severe fibrosis. In conclusion, a correlation was found between alcohol consumption and periportal inflammation. Fibrosis correlated with age, high enzymes levels and low platelets. AST and platelets were the best predictors for severe fibrosis.

Health-related quality of life among blood donors with hepatitis B and hepatitis C: longitudinal study before and after diagnosis.

INTRODUCTION: There is evidence that patients suffering from chronic hepatic diseases, including chronic hepatitis B and chronic hepatitis C, have a reduced health-related quality of life. The aim of this study was to evaluate the impact of the notification of test results for hepatitis B and hepatitis C on the quality of life of blood donors. METHODS: Over a 29-month period, this study assessed the quality of life of 105 blood donors with positive serological screening tests for hepatitis B and hepatitis C and donors who presented false-positive test results. The Medical Outcome Study 36-Item Short Form Health Survey Questionnaire was applied at three time points: (1) when an additional blood sample was collected for confirmatory tests; (2) when donors were notified about their serological status; and (3) when donors, positive for hepatitis B and hepatitis C, started clinical follow-up. Quality of life scores for the confirmed hepatitis B and hepatitis C groups were compared to the false-positive control group. RESULTS: The domains bodily pain, general health perception, social function, and mental health and the physical component improved significantly in donors with hepatitis C from Time Point 1 to Time Point 3. Health-related quality of life scores of donors diagnosed with hepatitis B and hepatitis C were significantly lower in six and four of the eight domains, respectively, compared to the false-positive control group. CONCLUSION: A decreased quality of life was detected before and after diagnosis in blood donors with hepatitis B and hepatitis C. Contrary to hepatitis B positive donors, the possibility of medical care may have improved the quality of life among hepatitis C positive donors.

Diagnosis and treatment of benign liver nodules: Brazilian Society of Hepatology (SBH) recommendations.

Space-occupying lesions of the liver may be cystic or solid. Ultrasonography is an extremely useful method for initial screening, and suffices for diagnosis of simple hepatic cysts. Complex cysts and solid masses require computed tomography or magnetic resonance imaging for confirmation. Wide surgical excision is indicated in cystadenoma or cystadenocarcinoma. Clinical and epidemiological data are important, as nodules in noncirrhotic livers are more likely to be benign. Hemangiomas, the most common benign tumors, require no follow-up after diagnostic confirmation if they are small and asymptomatic. Patients with giant, symptomatic hemangiomas or compression of adjacent structures should be referred to hepatobiliary centers for potential surgery. The genetic heterogeneity of hepatocellular adenomas and their epidemiology and prognosis prompted classification of these tumors into four subtypes based on histology and immunohistochemistry. The major complications of hepatocellular adenomas are rupture with bleeding and malignant transformation. Rupture occurs in approximately 30% of cases. The main risk factors are tumors size >5 cm and inflammatory subtype. Hepatocellular adenomas may enlarge during pregnancy due to marked hormonal stimulation. As oral contraceptive pills and anabolic steroids have associated with hepatocellular adenomas growth, particularly of the hepatocyte nuclear factor-1alfa subtype, these drugs should be discontinued. Focal nodular hyperplasia is the second most common benign tumor of the liver. It is most frequent in women aged 20 to 60, and 70% to 90% of cases are asymptomatic. In the absence of a central scar and/or other hallmarks of Focal nodular hyperplasia, with uncertainty between this diagnosis and hepatocellular adenoma, liver-specific contrast agents are indicated.

Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Different degrees of malnutrition and immunological alterations according to the aetiology of cirrhosis: a prospective and sequential study.

OBJECTIVES: In this work we investigated how immunological dysfunction and malnutrition interact in alcoholic and viral aetiologies of cirrhosis. METHODS: To investigate the matter, 77 cirrhotic patients divided in three aetiologies [Alcohol, HCV and Alcohol + HCV) and 32 controls were prospectivelly and sequentially studied. Parameters of humoral immunity (Components 3 and 4 of seric complement and immunoglobulins A M, G and E) and of cellular immunity (total leukocytes and lymphocytes in peripheral blood, T lymphocytes subpopulations, CD4+ and CD8+, CD4+/CD8+ ratio and intradermic tests of delayed hypersensitivity), as well as nutritional parameters: anthropometric measures, serum albumin and transferrin were evaluated. RESULTS: Multiple statistical comparisons showed that IgM was higher in HCV group; IgG was significantly elevated in both HCV and Alcohol + HCV, whereas for the Alcohol group, IgE was found at higher titles. The analysis of T- lymphocytes subpopulations showed no aetiologic differences, but intradermic tests of delayed hypersensitivity did show greater frequency of anergy in the Alcohol group. For anthropometric parameters, the Alcohol +HCV group displayed the lowest triceps skinfold whereas creatinine--height index evaluation was more preserved in the HCV group. Body mass index, arm muscle area and arm fat area showed that differently from alcohol group, the HCV group was similar to control. CONCLUSION: Significant differences were found among the main aetiologies of cirrhosis concerning immunological alterations and nutritional status: better nutrition and worse immunology for HCV and vice-versa for alcohol.