Two-year risedronate treatment for osteoporosis in patients with esophageal varices: a non-randomized clinical trial.

BACKGROUND: Bisphosphonates are the mainstay of osteoporosis treatment, but their use for patients with esophageal varices has been avoided due to the risk of esophagitis, which may cause variceal bleeding. Since most clinical trials assessing osteoporosis treatment last 2-3 years, this study aimed to evaluate a 2-year risedronate treatment for patients with esophageal varices and liver cirrhosis. METHODS: The study received Institutional Review Board approval, and the sample was divided into two groups according to bone mineral density (BMD). Cirrhosis severity and endoscopic findings at baseline were similar between the groups. The intervention group had 51 patients with osteoporosis, who received oral risedronate 35 mg weekly plus calcium and vitamin D supplements. The control group had 51 patients with osteopenia, receiving only the supplements. Scheduled esophagogastroduodenoscopies and BMD measurements were carried out. RESULTS: The adjusted esophagitis risk was higher in the intervention group; however, none of the subjects had digestive bleeding. Lumbar spine BMD increased in the intervention group (- 3.06 ± 0.71 to - 2.33 ± 0.90; p < 0.001) and in the control group (- 1.38 ± 0.77 to - 1.10 ± 1.05; p = 0.012). Femoral neck BMD did not change in the intervention group (- 1.64 ± 0.91 to - 1.71 ± 0.95; p = 0.220), but tended to decrease in the control group (- 1.00 ± 0.74 to - 1.09 ± 0.82; p = 0.053). CONCLUSION: Oral risedronate was effective and did not cause gastrointestinal bleeding in cirrhotic patients with esophageal varices under endoscopic surveillance.

Refining dual-energy x-ray absorptiometry data to predict mortality among cirrhotic outpatients: A retrospective study.

OBJECTIVE: The aim of this study was to compare the effects of muscle wasting according to measures obtained by different limb muscle mass indexes, to find the best mortality predictor among outpatients with cirrhosis. METHODS: Patients with liver cirrhosis (N = 210) were submitted to dual-energy x-ray absorptiometry (DXA). Appendicular muscle mass (AMM), AMM index (AMMI), upper limb muscle mass (ULMM), and ULMM index (ULMMI) were calculated. The Model for End-Stage Liver Disease, anthropometric measures, and the presence of ascites and edema were also registered. Multiple logistic regressions were performed to determine mortality predictors; the area under the receiver operating characteristic curve was used to establish the best cutoff point to predict mortality. RESULTS: The mean follow-up duration was 49 ± 15.59 mo. ULMM and ULMMI were clearly associated with mortality (P = 0.007 and 0.001, respectively), whereas AMM and AMMI were not. After calculating the cutoff points for men and women, the presence of a depleted ULMMI as a categorical variable was associated with a mortality risk 2.5 times higher. CONCLUSIONS: The results suggest that using ULMMI is better than AMMI for predicting mortality of outpatients with cirrhosis, thus offering a better measure to detect muscle wasting in this population using DXA.

Safety and efficacy of risedronate for patients with esophageal varices and liver cirrhosis: a non-randomized clinical trial.

Despite the high prevalence of osteoporosis in liver cirrhosis, the indication of bisphosphonates for patients with esophageal varices has been avoided due to risk of digestive mucosal damage. Therefore, this study aimed to evaluate the safety profile of risedronate treatment for patients with osteoporosis, liver cirrhosis and esophageal varices with low risk of bleeding. A total of 120 patients were allocated into two groups according to their bone mineral density measured by dual-energy X-ray absorptiometry. In the intervention group, 57 subjects with osteoporosis received oral risedronate at 35 mg weekly plus daily calcium and vitamin D supplementation. In the control group, 63 subjects with osteopenia received only calcium and vitamin D. The groups received the treatment for one year and underwent surveillance endoscopies at six and 12 months, as well as a control dual-energy X-ray absorptiometry after a 12-month follow-up. The study received Institutional Review Board approval. The groups had not only comparable Model for End-stage Liver Disease score and esophageal varices degree, but also similar incidence of digestive adverse effects. A significant improvement was achieved in the intervention group in the lumbar spine T score (p < 0.001). The results suggest that risedronate may be safely used in liver cirrhosis and esophageal varices with low bleeding risk under endoscopic surveillance, thus allowing bone mass recovery.

Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial.

Branched-chain amino acids increase the brain perfusion of patients with hepatic encephalopathy (HE), but the amino acid and the mechanisms involved are still unknown. This study compared brain perfusion and clinical improvement during leucine or isoleucine supplementation. After randomization, 27 subjects with cirrhosis and HE received leucine or isoleucine supplements for one year. Brain single Photon Emission Computed Tomography (SPECT) and dynamic brain scintigraphy (DBS) were performed pretreatment and at 1, 8 and 12 months of supplementation. Brain perfusion was increased only in the isoleucine group at 8 months of treatment by both SPECT and DBS (p < 0.001 and p = 0.05, respectively) and by SPECT at the 12th month (p < 0.05). This was associated with hepatic encephalopathy improvement at 8 and 12 months (p = 0.008 and 0.004, respectively), which was not observed in the leucine group (p = 0.313 and 0.055, respectively). Isoleucine supplementation achieved a better impact on brain perfusion restoration in HE.

Diagnosis and Management of Cirrhosis-Related Osteoporosis.

Management of cirrhosis complications has greatly improved, increasing survival and quality of life of the patients. Despite that, some of these complications are still overlooked and scarcely treated, particularly those that are not related to the liver. This is the case of osteoporosis, the only cirrhosis complication that is not solved after liver transplantation, because bone loss often increases after immunosuppressant therapy. In this review, the definitions of bone conditions in cirrhotic patients are analyzed, focusing on the more common ones and on those that have the largest impact on this population. Risk factors, physiopathology, diagnosis, screening strategies, and treatment of osteoporosis in cirrhotic patients are discussed, presenting the more striking data on this issue. Therapies used for particular conditions, such as primary biliary cirrhosis and liver transplantation, are also presented.

Phase angle is associated with advanced fibrosis in patients chronically infected with hepatitis C virus.

AIMS: The objective of this study was to evaluate the association of phase angle (PhA) with advanced liver fibrosis in patients chronically infected with hepatitis C virus (HCV). MAIN METHODS: One hundred sixty consecutive patients chronically infected with HCV were treated at the Hepatitis C outpatient care setting of our hospital from April 2010 to May 2011 and prospectively evaluated. Bioelectrical impedance analysis measurements were performed during the first hospital visit. Biochemical measurements and liver biopsy data were collected from the patients' medical records and included in the analysis only if they were performed within three months of the inclusion of the patient in the study. KEY FINDINGS: One hundred sixty consecutive patients were evaluated and 25 patients were excluded. A total of 135 patients with 49.8±11.4years old were studied. Among these patients, 60% were male and the PhA was 6.5±0.8°. Regarding the stage of fibrosis, patients with advanced fibrosis were older and had more insulin resistance and more inflammation compared with patients that had mild fibrosis. Logistic regression analysis revealed that PhA was a predictor of advanced fibrosis even when adjusted for gender, age, HOMA-IR, HDL-cholesterol and AST (OR: 0.227; CI 95%: 0.090-0.569; p: 0.013). The best PhA cut-off points associated with advanced fibrosis for the combined data, for females and for males were 6.43°, 5.94° and 6.72°, respectively. SIGNIFICANCE: PhA was predictor of advanced liver fibrosis in patients chronically infected with HCV. In the sample evaluated, for each one-degree decrease in PhA, the risk of advanced fibrosis increased more than four-fold.

Handgrip strength as a predictor of bone mineral density in outpatients with cirrhosis.

BACKGROUND AND AIM: Osteoporosis is well recognized as a cirrhosis complication; however, most studies assessing this condition included only patients on liver transplantation lists with an elevated rate of bone diseases. While general population studies show that handgrip strength is clearly associated with bone mineral density, until now this tool has not been applied to patients with cirrhosis in relation to their bone condition. This study aimed to evaluate whether handgrip strength, bone, and liver tests may be useful as predictors of bone disease in outpatients with cirrhosis. METHODS: One hundred twenty-nine subjects were included (77 men and 52 women). Dual-energy X-ray absorptiometry was applied to evaluate lumbar-spine and femoral-neck T scores. Osteoporosis/osteopenia rates were 26.3%/35.6% in the lumbar spine and 6.9%/41.8% in the femoral neck, respectively. Model selections were based on backward procedures to find the best predictors of low T scores. RESULTS: For lumbar spine, only low handgrip strength and high parathyroid hormone levels were clearly related to low T scores. For femoral neck, only age was associated with low T scores. CONCLUSIONS: Handgrip strength may serve as an effective predictor of low lumbar spine T score among outpatients with cirrhosis. As cirrhosis affects the lumbar spine more than the femoral neck, these results suggest that handgrip strength should be tested in all patients with cirrhosis as a first indicator of bone health.

Terapia nutricional nas doenças inflamatórias intestinais: artigo de revisão / Nutrition therapy in inflammatory bowel diseases: review article

OBJECTIVE: This article aims to discuss the role of nutrition therapy in Inflammatory Bowel Diseases according to its indications, contraindications, and the as main results obtained with prebiotics, probiotics, symbiotics and other nutritional interventions. Data source: We performed a literature review using the databases Pubmed, Scielo and Lilacs. Data synthesis: Inflammatory Bowel Diseases are chronic illnesses that affect primarily the gastrointestinal tract and are divided in two most common forms of presentation: Crohn's Disease and Ulcerative Colitis. The chronic inflammation can cause intestinal lesions, anorexia, nutrients malabsorption, oxidative stress and higher energy consumption, increasing the risk of malnutrition. Nutritional status is directly associated with the disease severity and malnutrition is a serious complication of inflammatory bowel diseases that worsens the patients' prognosis. Nutritional therapy is used to prevent or treat the malnutrition, to correct macro and micronutrients deficits and to reverse some of the metabolic and pathological consequences of these diseases. In the majority of patients, the nutrition therapy has an adjuvant role combined to medical or surgical treatments, but in some specific situations it can be the main treatment. CONCLUSIONS: Despite the benefits of nutritional therapy, more meta-analysis and double-blind controlled studies about these diseases are required to assure the good results obtained in some of the published trials.

OBJETIVO: O objetivo do artigo é discutir o papel da Terapia Nutricional nas Doenças Inflamatórias Intestinais de acordo com suas indicações e contraindicações, bem como os principais resultados com prebióticos, probióticos, simbióticos e outras intervenções nutricionais nessas doenças. Fonte dos dados: Foi realizada busca por artigos nas bases de dados: Pubmed, Scielo e Lilacs. Síntese dos dados: Doenças Inflamatórias Intestinais são doenças crônicas que acometem principalmente o trato gastrointestinal e se dividem em duas formas mais comuns de apresentação: Doença de Crohn e Retocolite Ulcerativa. A inflamação crônica pode causar lesões intestinais, anorexia, má absorção de nutrientes, estresse oxidativo e aumento do gasto energético, aumentando o risco de desnutrição. O estado nutricional está diretamente associado com a gravidade da doença e a desnutrição é uma complicação que piora o prognóstico do paciente. A terapia nutricional é utilizada para impedir ou corrigir a desnutrição, repor deficiências de macro e micronutrientes e reverter parte das consequências metabólicas patológicas dessas doenças. Na maior parte dos pacientes, a terapia nutricional atua como coadjuvante combinada ao tratamento clínico ou cirúrgico, mas em algumas situações específicas pode ser o principal tratamento. CONCLUSÃO: Apesar dos vários benefícios atingidos pelo uso da terapia nutricional, mais metanálises e estudos randomizados duplo cegos ainda são necessários para comprovar os efeitos de suplementos específicos, garantindo, dessa maneira, resultados positivos na sua aplicação

Ingestão proteica na encefalopatia hepática: panorama atual / Protein intake in hepatic encephalopathy: current concepts

Hepatic encephalopathy is a severe complication of cirrhosis and comprises a complexand multifactorial pathophysiology. However, ammonia exchange between different tissues still deserves attention in relation to neurological alterations. Hepatic encephalopathy treatment remains focused on the trigger factor correction and the ammonia formation. Therefore, it was believed that high-proteic diets could lead to hepatic encephalopathy through the accumulation of nitrogen compounds in the gastrointestinal tract, which could increase production and absorption of ammonia.Currently, it is known that proteic restriction is harmful to cirrhotic patients, but it isstill utilized. Malnutrition is highly prevalent among cirrhotic individuals with hepatic encephalopathy, thus indicating a nutritional risk which is clearly related to higher mortality rates. Furthermore, there is an increase in the protein needs of these patients and also a relationship between the loss of lean mass and hyperammonaemia. For these and other factors herein discussed, today's global guidelines recommend the ingestion of higher protein levels for patients with hepatic encephalopathy

A encefalopatia hepática é uma complicação grave da cirrose e envolve uma fisiopatologia complexa e multifatorial. Entretanto, a influência da amônia nos diferentes tecidos ainda merece atenção no que se refere às manifestações neuropatológicas. O tratamento da encefalopatia hepática permanece focado na correção do distúrbio desencadeante e na diminuição da formação da amônia a partir do cólon. Por conta disso, acreditava-se que dietas ricas em proteínas poderiam desencadear a encefalopatia hepática por meio do aporte de nitrogênio no trato gastrointestinal, podendo aumentar a produção e a absorção da amônia. Atualmente, sabe-se que a restrição proteica é prejudicial para portadores de cirrose, embora ainda utilizada. A desnutrição é prevalente entre indivíduos cirróticos com encefalopatia hepática, indicando um estado nutricional de risco que está nitidamente relacionado às maiores taxas de mortalidade. Além disso, há um aumento nas necessidades proteicas desses pacientes e uma relação entre a perda de massa magra e a hiperamoniemia. Com base em tais fatores, os guidelines atuais mundiais recomendam dieta hiperproteica para pacientes com encefalopatia hepática.

Embolization of splenorenal shunt associated to portal vein thrombosis and hepatic encephalopathy.

UNLABELLED: Hepatic encephalopathy (HE) is a cognitive disturbance characterized by neuropsychiatric alterations. It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts. The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration. Therefore, the embolization of these shunts has been performed to control HE manifestations, but the presence of portal vein thrombosis is considered a contraindication. In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt. CASE REPORT: a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma, even without precipitant factors. She had a wide portosystemic shunt and also portal vein thrombosis. The abdominal angiography confirmed the splenorenal shunt and showed other shunts. The larger shunt was embolized through placement of microcoils, and the patient had no recurrence of overt HE. There was a little increase of esophageal and gastric varices, but no endoscopic treatment was needed. Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients, portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization. However, in particular cases with many shunts and severe HE, we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery. In conclusion, we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis. As the patient had other shunts, she was successfully treated by embolization of the larger shunt.

Redução do MELD em pacientes na lista de transplante hepático após o uso de aminoácidos de cadeia ramificada: relato de caso / Reduction of MELD in patients on the liver transplant list after using chain amino acids: case report

A cirrose hepática (CH) é uma doença com altas taxas de mortalidade e que apresenta, como único tratamento definitivo, o transplante hepático (TH). Infelizmente, nem todos os pacientes têm acesso ao TH e muitos acabam morrendo ainda na lista de transplante. O uso de aminoácidos de cadeia ramificada (AACR) já é amplamente conhecido como tratamento eficaz para a melhora da qualidade de vida destes pacientes. Neste relato, pela primeira vez, documentou-se uma grande melhora clínica e laboratorial em um paciente após o tratamento com AACR, que permitiu ao paciente sair inclusive da lista de transplante. Além da diminuição do escore MELD, houve reestabilização do peso corporal e melhora da qualidade de vida, documentada pelo questionário SF-36.

Liver cirrhosis (LC) is a disease with high mortality rates and its only definitive treatment is the orthotopic liver transplantation (OLT). Unfortunately, not all patients have access to OLT and many of them end up dying on the transplant waiting list. The use of branched chain amino acids (BCAA) is widely known as an effective treatment for improving the quality of life of these patients. For the first time, in this paper we documented a great improvement of clinical and laboratorial tests of a patient treated with BCAA, which allowed him to be out of the transplant waiting list. In addition to the increase of the MELD score, the patient achieved restabilization of body weight and recovery of the quality of life registered by the SF-36 questionnaire.