Probiotics and synbiotics may improve liver aminotransferases levels in non-alcoholic fatty liver disease patients.

Non-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of liver diseases ranging from simple steatosis to steatohepatitis (NASH). Alterations in intestinal microbiota and inflammatory response may play a key role in disease progression and development of complications in liver diseases, mainly in cirrhosis and NASH. The aim of this study was to perform a systematic review on randomized clinical trials (RCTs) testing probiotics, prebiotics or both (synbiotics) in the treatment of NAFLD in adult patients. After the screening process, 9 full-text articles were included in the review and 6 studies were excluded. Three randomized controlled trials were finally included in the qualitative synthesis. All patients in all the 3 studies were randomized to receive different formulations of probiotics, synbiotics or placebo. Reductions in aminotransferases were observed in the treated group in 2 of the studies. However, in one study reductions were also detected in the control group. In conclusion, the available evidence precludes, for the moment, recommendations on the use of pre and probiotics in clinical practice.

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.

Aspartate aminotransferase-to-platelet ratio index (APRI) for the non-invasive prediction of esophageal varices.

BACKGROUND & AIMS: Variceal bleeding is a dramatic and common complication of cirrhosis, and, therefore, endoscopy is recommended for the screening of EV (esophageal varices) in every cirrhotic. This study evaluates the capacity of APRI (aspartate aminotransferase-to-platelet ratio index) in non-invasively predicting EV. MATERIAL AND METHODS: This cross-sectional study evaluated cirrhotics for their APRI value and the presence of EV, with a cutoff point of 1, 3; platelet count, spleen diameter, PC/SD (platelet count/ spleen diameter ratio), aspartate aminotransferase/alanine aminotransferase ratio, Child-Pugh score and MELD (model for end-stage liver disease) score were also studied. RESULTS: The study included 164 cirrhotics, 59.7% male, with a mean age of 56.7 years. APRI demonstrated a sensitivity of 64.7% (95% confidence interval-95%CI = 0.56-0.73), specificity of 72.7% (95%CI = 0.59-0.86), positive predictive value of 86.5% (95%CI = 0.79-0.94), negative predictive value of 43.2% (95%CI = 0.32-0.55). In the univariate analysis, platelet count, spleen diameter, Child and MELD scores, PC/SD and APRI were related to EV (p < 0.05). In the logistic regression, only platelet count and Child score were associated to EV (p < 0.05). CONCLUSION: APRI is not an independent factor for the prediction of EV. Its sensitivity, specificity and predictive values are insufficient for the index to be used for the screening of EV in cirrhotics.

Post-transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience.

Post-transplant lymphoproliferative disorder (PTLD) is a major and potentially life-threatening complication after solid-organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (± 14) yr with a mean time of 39.7 (± 35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second-line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post-PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post-PTLD mortality included lactate dehydrogenase ≥ 250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long-term survival is possible.

An update on the management of hepatitis C: guidelines for protease inhibitor-based triple therapy from the Latin American Association for the Study of the Liver.

Hepatitis C is a common cause of end-stage liver disease, and the main indication for liver transplantation in Latin America. Treatment of hepatitis C infected patients improves important long-term outcomes as mortality. Sustained viral response is reached in near 50% of patients with the previous management based in pegylated interferon and ribavirin. Recently new drugs were available increasing sustained viral response significantly, changing the standard of care to triple therapy. This guidelines provides a framework for practitioner in Latin America, to the management of patients with hepatitis C chronic infection. 

Current indications for the use of albumin in the treatment of cirrhosis.

The role of proteins in the maintenance of colloid osmotic pressure has been described by Starling since 1896. For many decades, the importance of albumin was associated exclusively to its colloid osmotic function. More recently, other properties of albumin have been demonstrated, such as: carrying different substances, anti-inflammatory activity, preserving capillaries permeability, anti-oxidant role. It is noteworthy that, in decompensated cirrhosis, there is qualitative and quantitative decrease in albumin function. This is why, when we use it, we must have in mind its pharmacological role, as well as its colloid osmotic function. Currently, albumin has three major indications in the treatment of cirrhosis. The first would be in the treatment of tense or refractory ascites, when large-volume paracentesis are accomplished, maily when more than 4-5L of ascites are drained, in order to avoid post-paracentesis dysfunction. The second would be in cases of spontaneous bacterial peritonitis, avoiding renal impairment and increasing survival; it is formally indicated when bilirubin is greater than 4 mg/dL or creatinine is greater than 1 mg/dL. Finally, we understand its use associated to terlipressin seems to be the best treatment strategy for type I hepatorenal syndrome. Hence, its judicial use is of great relevance and benefit in the treatment of these complications of the cirrhotic patient.

Treatment of HCV infection in patients with cirrhosis.

The treatment of patients with cirrhosis has the following purposes: to prevent the complications of the disease; to allow for the regression of cirrhosis; and to prevent reinfection in the graft in patients undergoing liver transplantation. When the sustained viral response is evaluated in patients with cirrhosis, especially in those with decompensated disease, it is noted to be lower than that of patients with chronic hepatitis, and with a higher possibility of complications of the treatment. Based on a review of the literature, we conclude that we should treat patients with compensated cirrhosis, probably also those with portal hypertension, and patients with decompensated cirrhosis only when included on the transplant list, as long as Child B with HCV genotype 2 (possibly 3) and preferably after clinical compensation.

Sustained virological response according to the type of early virological response in HCV and HCV/HIV.

BACKGROUND: The most important factors to predict the sustained virological response (SVR) are the genotype and the fibrosis grade, although there are other predictive factors to be considered, mainly in HCV/HIV coinfected patients. AIM: To evaluate different prognostic factors to obtain the SVR in HCV monoinfected and HCV/HIV coinfected genotype 1 patients emphasizing the type of early virological response (EVR)-complete or partial. METHODS: This is a cohort study, retrospective, where the registers of HCV monoinfected or HCV/HIV coinfected patients, genotype 1, treated with pegylated interferon + ribavirin were reviewed. The prognostic factors: age greater than 40 years, viral load higher than 600,000UI/mL, and fibrosis grade (score METAVIR) were evaluated pre-treatment, and also the EVR considering the reduction of 100 times of the basal viral load (partial EVR) or negative PCR (complete EVR) in the week 12. In the statistical analysis, multivariate analysis was used. The significance level adopted was 5%. RESULTS: There were 323 HCV monoinfected and 59 HCV/HIV coinfected. The SVR was 35.3% in monoinfected and 23% in coinfected patients. The worst results was observed in those with age greater than 40 years, high viral load, pronounced fibrosis (F4) and partial EVR, with an expected probability of 1.9% for SVR in those coinfected and 3.8% in monoinfected. In conclusion, patients with cirrhosis HCV genotype 1, age greater than 40 years, high viral load, coinfected with HIV or not, will present a low SVR if did not obtain negative PCR in week 12, and should be evaluated for discontinuation.

Etiology of hepatocellular carcinoma in Latin America: a prospective, multicenter, international study.

BACKGROUND/AIMS: No prospective study has been published investigating etiology of HCC in Latin America. The primary aim of this prospective study was to analyze the etiology of liver disease in patients with HCC from our area. Secondary aims were to evaluate staging using Okuda and BCLC classifications; and percentage of patients receiving treatment. METHODS: The Governing Board of the Latin American Association for the Study of the Liver designed the protocol. During a 18 month period, all members were invited to load their incident HCC cases on line. RESULTS: 240 cases from 9 countries were uploaded, 174 were male (72.5%), median age was 64 years, interquartile range 57-72. In 85.4% of cases, patients had underlying cirrhosis. Main etiological factors were: HCV in 74 patients (30.8%), alcohol in 49 (20.4%), cryptogenic cirrhosis in 35 (14.6%), HBV in 26 (10.8%), HCV plus alcohol in 14 (5.8%). Considering the combinations, hepatitis C was shown in 91 patients (38%); chronic alcoholism in 68 patients (28%); and hepatitis B in 33 patients (14%). There were no significant differences between the groups in the age at diagnosis. Percentage of male gender was higher in groups of alcohol (94%), HCV plus alcohol (93%) and HBV (85%) than in cryptogenic cirrhosis (60%) and HCV (59%) (p<0.001). CONCLUSIONS: Our prospective study showed that hepatitis C is the more frequent etiology of HCC in Latin America, followed by alcoholic cirrhosis. Demographical results showed a male predominance (male:female ratio 2.6) with an important proportion of patients being diagnosed at their sixties.

Percutaneous ethanol injection before liver transplantation in the hepatocellular carcinoma.

BACKGROUND/OBJECTIVES: The study evaluates the outcome of patients who performed orthotopic liver transplantation (LT) as treatment for hepatocellular carcinoma (HCC), with percutaneous ethanol injection (PEI) while on the waiting list, verifying the effectiveness of this treatment in producing tumor necrosis and avoiding dropout and identifying treatment-related complications. MATERIAL AND METHODS: Medical records of 97 patients on the waiting list for LT at Hospital Clinic of Barcelona were examined. Sixty-two (56.3%) patients had been treated with PEI (group 1); 35 (31.8%) had not received any anti-tumor therapy before LT (group 2). RESULTS: Complete necrosis of the tumor was observed in 38/59 (64.3%) patients. The presence of additional nodules in the explant and the diameter of the main tumor of group 1 was significantly lower than in group 2 (p = 0.002). Dropout related to tumor progression occurred in 4.8% and 8.5%, and tumor recurrence in 5% and 6.2% for groups 1 and 2, respectively. Major complications were not evidenced after 421 PEI sessions and there was no tumor implant in the needle traject. CONCLUSIONS: In conclusion, the percutaneous treatment of HCC with PEI is a safe and effective method before the LT.

Impact of human immunodeficiency virus infection in patients infected with the hepatitis C virus.

BACKGROUND/AIMS: The objective of the present study is to evaluate the impact of human immunodeficiency virus (HIV) in patients with hepatitis C virus (HCV) infection. METHODS: Three different groups of patients were considered: group 1, 385 HCV/HIV coinfected; group 2, 198 HIV monoinfected; and group 3, 311 HCV monoinfected. Demographic and epidemiological data were collected. Blood tests included anti-HCV, HCV-RNA test, genotyping, CD4 cell count, anti-HIV, and HIV viral load. Treatment with interferon and ribavirin was proposed. The fibrosis progression rate was assessed. RESULTS: The most prevalent risk factor in the group of coinfected was the use of intravenous drugs; in the HIV monoinfection group, heterosexual relations at risk; in the HCV monoinfection group, the transfusion of blood. There was no difference concerning the distribution of genotypes or HCV viral load between groups 1 and 3. Although the mean time of duration of HCV infection was greater in group 3 than in group 1, there was no difference when the fibrosis progression rate was evaluated. The response to treatment was similar. CONCLUSION: In the present series there was no relevant impact of HCV infection in patients with HIV.

Renal impairment after spontaneous bacterial peritonitis: incidence and prognosis.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is an important complication in cirrhotic patients. The aim of the present study was to assess the incidence, predictive factors and prognosis for renal impairment (RI) after SBP in cirrhotic patients from southern Brazil. METHODS: Of the 1030 hospitalizations evaluated, 114 episodes of SBP were diagnosed in 94 patients (mean age 49 years; 76.59% men). SBP diagnosis was established when the ascitic fluid polymorphonuclear cell count was equal to or greater than 250 cells/mm3. Five cases were excluded. The variables assessed as possible predictors of steady or progressive RI were blood urea nitrogen and creatinine levels before the diagnosis of SBP; type of infection, antibiotic prophylaxis, first episode or recurrent SBP, presence of gastrointestinal bleeding and hepatic encephalopathy during hospitalization, SBP resolution, Child-Pugh classification, levels of blood pressure, ascitic fluid and blood polymorphonuclear cell count, bacteriological data (positive and negative ascitic fluid culture), albumin, bilirubin, sodium and prothrombin time at the moment of diagnosis. RESULTS: The incidence of SBP was 11.07%. In 61 (55.96%) episodes, SBP was associated with RI (transient in 57.37%; steady in 19.67%; and progressive in 22.95%). The mortality rate associated with progressive RI was 100%; 58.33% with steady RI; and 2.85% with transient RI. The mortality rate in patients with or without RI was 36.07% and 6.25%, respectively (P<0.001). The level of creatinine (greater than or equal to 1.3mg/dL) before the diagnosis of SBP and the rate of infection resolution were the only predictors of RI in the multivariate analysis. CONCLUSIONS: RI after SBP is a common complication, and indicates a poor prognosis for this infection. High levels of creatinine before infection and the rate of infection resolution are independent predictors of RI.