Long-standing donor diabetes and pathologic findings are associated with shorter allograft survival in recipients of kidney transplants from diabetic donors.

Approximately 6% of deceased kidney donors (DKDs) are diabetic; their kidneys may be associated with worse allograft survival, but published studies suggest that recipient diabetes status has a greater impact on mortality and survival. Since biopsy findings are the most common reason for organ discard, we sought to understand histologic and clinical factors that influence graft survival in patients who receive a kidney from a diabetic DKD. We retrospectively reviewed our institutional experience from 2005 to 2019, and re-evaluated pre-implantation and earliest post-transplant biopsies. Histologic findings were compared against a control cohort of non-diabetic DKD. Of 829 adult DKD transplants, 37 (4.5%) came from diabetic donors. There was no significant difference in diabetic vs. non-diabetic DKD graft survival for all-comers; however, when stratified by duration of donor diabetes, donor diabetes ≥6 years was associated with graft failure. In 25 patients with post-transplant biopsies available, diabetic DKD allografts had significantly greater non-glomerular chronic injury than non-diabetic DKD allografts. Moderate arteriolar hyalinosis (in 24%), moderate tubular atrophy and interstitial fibrosis (IFTA, in 36%), and diabetic glomerulopathy (in 24%) on early post-transplant biopsy were associated with allograft failure. Pre-implantation frozen section discrepancies were more common in long-standing donor diabetes, and arteriolar hyalinosis and IFTA scores on frozen accurately prognosticated graft loss. There was no morphologic improvement in lesions of diabetic nephropathy on short-term follow-up. In conclusion, donor diabetes ≥6 years, and histologic findings on frozen section and early post-transplant biopsy are associated with diabetic DKD allograft loss.

Long-term albumin administration in patients with cirrhosis and ascites: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Ascites is a common complication of cirrhosis, and it is associated with increased mortality. The aim of this study was to evaluate the efficacy of long-term albumin administration in decreasing mortality and other complications of patients with cirrhosis and ascites. METHODS: A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials evaluating long-term albumin administration in patients with cirrhosis and ascites were considered eligible, as long as at least one of the following outcomes was evaluated: mortality, recurrence of ascites/need for paracentesis, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. Meta-analysis was performed using the random-effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42019130078). RESULTS: The literature search yielded 1517 references. Five randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis, involving 716 individuals. Patients receiving long-term albumin had significantly lower risk of recurrence of ascites/need for paracentesis when compared with controls (risk ratio = 0.56, 95% confidence interval = 0.48-0.67, P < 0.00001). There was no evidence of significant difference between the long-term albumin and control groups regarding mortality, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. CONCLUSIONS: Long-term albumin administration in patients with cirrhosis and ascites decreases recurrence of ascites/need for paracentesis. At this point, there is no evidence of significant benefits of long-term albumin administration regarding mortality or other complications of cirrhosis.

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.

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.

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.

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.

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.

Angioplasty vs stent in the treatment of transplant renal artery stenosis.

OBJECTIVE: To compare outcomes between percutaneous transluminal angioplasty and stent placement in the treatment of transplant renal artery stenosis (TRAS). METHODS: We retrospectively studied patients who underwent angiography for TRAS between 1/1/2008 and 9/20/2016 at 1 center. We compared the rates of restenosis in patients who were treated with angioplasty alone vs those who were treated with stenting. Secondary outcomes included serum creatinine and blood pressure after intervention and graft and patient survival. RESULTS: A total of 82 patients were identified as having TRAS after angiography. Restenosis occurred in 28% (16 of 58) of the angioplasty patients compared with 8% (2 of 24) of the stented patients (P = .04). Repeat angiography occurred in 14% (8 of 58) of angioplasty patients vs 13% (3 of 24) of stented patients (P = .9). The stented group had significantly higher pre-intervention stenosis (71% vs 64%, P = .01) and lower postintervention stenosis (4% vs 30%, P < .001). Serum creatinine and blood pressures were not significantly different between the 2 groups at 30, 90, or 360 days postintervention. There was no statistically significant difference in graft or patient survival between groups (P = .37). CONCLUSIONS: Stent placement resulted in fewer cases of restenosis compared with angioplasty alone, although no benefit in terms of serum creatinine, blood pressure, or patient and graft survival was shown.

Hepatorenal syndrome: Current concepts related to diagnosis and management.

 Renal failure in cirrhotic patients is a very severe condition. Hepatorenal syndrome has the worst prognosis among all causes of kidney failure in such patients. Hepatorenal syndrome is diagnosed especially in cirrhotic patients with ascites who develop loss renal function, despite diuretic suspension and volume expansion with albumin and for whom other causes of kidney injury have been excluded. Patients with hepatorenal syndrome should be treated with a vasoconstrictor in combination with albumin as a bridge to receiving a liver transplant. The vasoconstrictor of choice is terlipressin or noradrenaline. In spite of higher drug-related costs associated to terlipressin, initial evidence demonstrates that, considering all direct medical costs involved, the treatment strategy using terlipressin is probably more economical than that using noradrenaline.

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.

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.

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality. This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease. This makes the management of patients more challenging, since physicians must take into consideration two different conditions, the chronic liver disease and the tumor. The underlying liver disease has several implications in clinical practice, because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC, obstacles in surveillance, and differences in the efficacy of the treatment against HCC. A shift in the prevalence of liver diseases has been evident over the last few years, with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance. Therefore, in an era of personalized medicine, it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

Retrospective analysis of the efficacy and survival associated with cTACE and DEB-TACE in the palliative treatment of hepatocellular carcinoma: experience of a tertiary care hospital in southern Brazil.

Objective: To compare conventional transarterial chemoembolization (cTACE) and drug-eluting bead TACE (DEB-TACE) in terms of efficacy, survival, and adverse effects in patients with hepatocellular carcinoma who are not candidates for curative therapy. Materials and Methods: This was a retrospective study of patients with hepatocellular carcinoma who underwent cTACE or DEB-TACE for palliative treatment between January 2009 and December 2021. The Kaplan-Meier method was used for survival analysis. Values of p < 0.05 were considered statistically significant. Results: We evaluated 268 patients, of whom 70 underwent DEB-TACE and 198 underwent cTACE. There was no significant difference between the groups regarding sex, age, or etiology of cirrhosis. The proportion of patients achieving a complete response on imaging examinations was higher in the cTACE group (31.8% vs. 16.1%), whereas that of patients achieving a partial response was higher in the DEB-TACE group (33.9% vs.19.7%), and the differences were significant (p = 0.014). The mortality rate was similar between the groups. The survival rate in the DEB-TACE and cTACE groups, respectively, was 87.0% and 87.9% at one year, 35.1% and 32.9% at three years, and 20.5% and 18.1% at five years (p = 0.661). There was no significant difference between the DEB-TACE and cTACE groups in terms of the frequency of adverse events (7.1% vs. 17.8%; p = 0.052). The most common complication in both groups was post-embolization syndrome. Conclusion: Although a complete response was more common among the patients who underwent cTACE, there was no difference in survival between the groups and the frequency of adverse events was similar.

Objetivo: Comparar a eficácia, sobrevida e efeitos adversos entre cTACE e DEB-TACE em pacientes com carcinoma hepatocelular não candidatos a terapia curativa. Materiais e Métodos: Estudo retrospectivo de pacientes com carcinoma hepatocelular submetidos a cTACE ou DEB-TACE para tratamento paliativo entre janeiro de 2009 e dezembro de 2021. Foi utilizado o método Kaplan-Meier para análise de sobrevida. Valor de p < 0,05 foi considerado estatisticamente significante. Resultados: Foram avaliados 268 pacientes, dos quais 70 foram submetidos a DEB-TACE e 198 foram submetidos a cTACE. Não houve diferença em relação ao sexo, idade e etiologia da cirrose. O grupo cTACE apresentou maior porcentual de resposta completa em exames de imagem (31,8% vs. 16,1%) e o grupo DEB-TACE apresentou maior porcentual de resposta parcial (33,9% vs.19,7%), com valor de p = 0,014. A mortalidade foi semelhante. As taxas de sobrevivência para os grupos DEB-TACE e cTACE foram 87,0% e 87,9% em um ano, 35,1% e 32,9% em três anos e 20,5% e 18,1% em cinco anos, respectivamente (p = 0,661). Em relação à frequência de eventos adversos, não houve diferença significativa entre os grupos (7,1% na DEB-TACE vs. 17,8% na cTACE; p = 0,052). A complicação mais comum, em ambos os grupos, foi a síndrome pós-embolização. Conclusão: Embora tenha sido observada maior frequência de resposta completa em pacientes submetidos a cTACE, não houve diferença na sobrevida dos pacientes entre os grupos. A taxa de eventos adversos também foi semelhante.

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.