Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region.

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).

Infectious and non-infectious diseases burden among Haitian immigrants in Chile: a cross-sectional study.

Chile has become a popular destination for migrants from South America and the Caribbean (low- and middle-income countries migration). Close to 200.000 Haitian migrants have arrived in Chile. Infectious and non-infectious disease burden among the Haitian adult population living in Chile is unknown. This study aimed to acquire the basic health information (selected transmissible and non-transmissible conditions) of the Haitian adult population living in Chile. A cross-sectional survey was performed, inviting Haitian-born residents in Chile older than 18 years old. Common conditions and risk factors for disease were assessed, as well as selected transmissible conditions (HIV, HBV, and HCV). 498 participants (60.4% female) from 10 communities in two regions of Chile were surveyed. Most subjects had never smoked (91.5%), and 80% drank less than one alcohol unit per month. The mean BMI was 25.6, with 45% of participants having a normal BMI (20-25). Hypertension was present in 31.5% (33% in the 25-44 age group). Prevalence of HIV was 2.4% (95 CI 1.3-4.2%), hepatitis B (HBsAg positive) was 3.4% (95 CI 2.1-5.5%), and hepatitis C was 0% (95 CI 0.0-0.9%). Quality of life showed a significant prevalence of depression and anxiety markers, particularly in those arriving in Chile less than 1 year ago. Low prevalence of obesity, diabetes, smoking, and drinking and estimated cardiovascular risk were found. Nonetheless, hypertension at a younger age, disproportionately higher prevalence of HIV and HBV infection and frequent markers of anxiety and depression were also found. Public policies for detecting and treating hypertension, HIV, and HBV screening, offering HBV vaccination, and organizing mental health programs for Haitian immigrants, are urgently needed.

The liver in times of COVID-19: What hepatologists should know.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) pandemic poses a serious threat to healthcare systems globally. Information regarding how the infection affects the liver and relevance of pre-existing liver disease as a risk factor for acquiring the infection or having a severe disease are still scarce. Also, considerations in liver transplant patients, those having hepatocellular carcinoma or under immunosuppressive therapy are being matter of analysis as information is being generated. Different treatments for COVID-19 are currently under study, some of which may be associated to hepatotoxicity. In the present review we discuss current data on the COVID-19 and liver, aiming to provide hepatologists with updated information to face this pandemic.

Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents.

BACKGROUND & AIMS: Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS: We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS: During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS: Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.

High prevalence of hepatic steatosis and vascular thrombosis in COVID-19: A systematic review and meta-analysis of autopsy data.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disease can frequently affect the liver. Data on hepatic histopathological findings in COVID-19 is scarce. AIM: To characterize hepatic pathological findings in patients with COVID-19. METHODS: We conducted a systematic review with meta-analysis registered on PROSPERO (CRD42020192813), following PRISMA guidelines. Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test. Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed. Articles including less than ten patients were excluded. Proportions were pooled using random-effects models. Q statistic and I 2 were used to assess heterogeneity and levels of evidence, respectively. RESULTS: We identified 18 studies from 7 countries; all were case reports and case series from autopsies. All the patients were over 15 years old, and 67.2% were male. We performed a meta-analysis of 5 studies, including 116 patients. Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1% [95% confidence interval (CI): 46.2-63.8], congestion of hepatic sinuses 34.7% (95%CI: 7.9-68.4), vascular thrombosis 29.4% (95%CI: 0.4-87.2), fibrosis 20.5% (95%CI: 0.6-57.9), Kupffer cell hyperplasia 13.5% (95%CI: 0.6-54.3), portal inflammation 13.2% (95%CI: 0.1-48.8), and lobular inflammation 11.6% (95%CI: 0.3-35.7). We also identified the presence of venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis. CONCLUSION: We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features. Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation. Further studies are needed to establish the mechanisms and implications of these findings.

Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma.

BACKGROUND & AIMS: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. METHODS: This was a prospective multicentre cohort study from Latin America including 1400 F1-F4-treated patients with DAAs (F3-F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. RESULTS: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child-Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. CONCLUSIONS: Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.

Trasplante hepático exitoso en un paciente portador del Virus de la Inmunodeficiencia Humana (VIH) / Liver transplantation in a patient with human immunodeficiency virus (HIV): case report

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.

A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America. METHODS: From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were considered. Etiology of liver disease was confirmed in the explant. RESULTS: Participating LT centers per country included 2 from Brazil (n=191), 5 transplant programs from Argentina (n=98), 2 from Colombia (n=65), 4 from Chile (n=49), 2 from Mexico (n=12), and 1 from Peru (n=11) and Uruguay (n=9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005-06 to 26% in 2011-12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD. CONCLUSION: There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.

Results of Liver Transplantation for Hepatocellular Carcinoma in a Multicenter Latin American Cohort Study.

BACKGROUND AND AIMS: Heterogeneous data has been reported regarding liver transplantation (LT) for hepatocellular carcinoma (HCC) in Latin America. We aimed to describe treatment during waiting list, survival and recurrence of HCC after LT in a multicenter study from Latin America. MATERIAL AND METHODS: Patients with HCC diagnosed prior to transplant (cHCC) and incidentally found in the explanted liver (iHCC) were included. Imaging-explanted features were compared in cHCC (non-discordant if pre and post-LT were within Milan, discordant if pre-LT was within and post-LT exceeding Milan). RESULTS: Overall, 435 patients with cHCC and 92 with iHCC were included. At listing, 81% and 91% of cHCC patients were within Milan and San Francisco criteria (UCSF), respectively. Five-year survival and recurrence rates for cHCC within Milan, exceeding Milan/within UCSF and beyond UCSF were 71% and 16%; 66% and 26%; 46% and 55%, respectively. Locoregional treatment prior to LT was performed in 39% of cHCC within Milan, in 53% beyond Milan/within UCSF and in 83% exceeding UCSF (p < 0.0001). This treatment difference was not observed according to AFP values (≤100, 44%; 101-1,000, 39%, and > 1,000 ng/mL 64%; p = 0.12). Discordant imaging-explanted data was observed in 29% of cHCC, showing lower survival HR 2.02 (CI 1.29; 3.15) and higher recurrence rates HR 2.34 when compared to AFP <100 ng/mL. Serum AFP > 1,000 ng/mL at listing was independently associated with a higher 5-year recurrence rate and a HR of 3.24 when compared to AFP <100 ng/mL. CONCLUSION: Although overall results are comparable to other regions worldwide, pre-LT treatment not only considering imaging data but also AFP values should be contemplated during the next years.

Nuevas terapias orales de acción directa para tratamiento de virus de hepatitis C (VHC) / Direct antivirals for the treatment of chronic hepatitis C virus infection: experience in 106 patients

Background: The availability of direct-acting antivirals (DAA) for the treatment of chronic hepatitis C virus (HCV) infection is just starting to expand in Chile. Aim: To report the initial experience of patients treated with DAA and their evolution after treatment. Material and Methods: Prospective cohort study, from June 2013 to August 2016 of patients treated with DAA for HCV in three clinical centers. The presence of cirrhosis, clinical and laboratory features; adverse events (AE) and post-treatment changes in liver function were evaluated. Sustained viral response at 12 weeks post-treatment (SVR12) was determined. Results: One hundred six patients aged 58 ± 13 years, 54% males, were included. HCV genotype 1b was present in 88% and 47% had cirrhosis. Treatment regimens were asunaprevir + daclatasvir (DCV) in 17% of patients, paritaprevir / ritonavir / ombitasvir + dasabuvir in 33%, sofosbuvir (SOF) + DCV in 19%, and SOF + ledipasvir in 30%. Twenty five percent of patients used generic drugs. SVR12 was 92.1%, with no differences between generic and brand-name drugs. Serious AE were recorded in 22% of patients, being more common in those with cirrhosis (34% vs 11.5%, p < 0.01). At 12 weeks post-treatment follow-up, there was a decrease in aminotransferase values (p < 0.01), improvement in Child-Pugh score (5.9 vs. 5.5, p = 0.03) and decreased presence of ascites (p = 0.02). Conclusions: In our setting, DAA for HCV was highly effective and safe in non-cirrhotic patients. Hepatic function and inflammation improved at 12 weeks of follow-up. AE were common in patients with cirrhosis, suggesting that these patients should be treated by experienced teams. Generic drugs had similar effectiveness compared to originals.

Validation of the Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Chilean-Hispanic Patients.

INTRODUCTION AND AIM: In 2008 the International autoimmune hepatitis (AIH) Group proposed the simplified diagnostic criteria for this disease. The original cohort study was performed in 11 international centers, but validation studies are scarce in Latin-America. The aim of this study is validate these criteria in Hispanic patients. MATERIAL AND METHODS: A retrospective cohort of patients undergoing percutaneous liver biopsy and follow-up of at least 12 months was recruited from a Chilean University hospital. Patients with previous immunosuppressive therapy and liver transplant recipients were excluded. The diagnostic accuracy was analyzed using as gold standard the clinical course during long-term follow-up. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and area under the ROC curve (AUROC) were calculated. RESULTS: Four hundred eighty one patients were evaluated, 294 were included. 218 (74.15%) were female, mean age 48.5 (± 12.3) years, mean follow-up 34 (± 18) months. 66 patients had AIH or overlap syndrome (22.45%), 96 (32.65%) non-alcoholic steatohepatitis, 40 (13.61%) primary biliary cholangitis, 31 (10.54%) hepatitis C, 8 (2.72%) hepatitis B, 53 (18.02%) other etiologies. The AUROC for AIH simplified criteria was 0.976. Using a cutoff ≥ 6 and ≥ 7 points, the sensitivity was 86.4% and 54.6%; specificity, 98.7% and 99.6%; PPV, 95% and 97.3%; and NPV, 96.2% and 88.6%, respectively. CONCLUSION: Simplified criteria for the diagnosis of AIH have a high accuracy in our Chilean-Hispanic cohort. The female gender is strongly associated to AIH and could help in difficult cases. Further studies with a prospective design are necessary to confirm these observations.

Hepatitis C virus may have an entero-hepatic cycle which could be blocked with ezetimibe.

Hepatitis C virus can lead to chronic infection, cirrhosis and hepatocellular carcinoma. With more than 170 million people infected worldwide, eradication remains a challenge even with the revolutionary current direct antiviral agents (DAAs). The risk of resistance, the safety profile in some populations, the genotype specificity and the high price of current DAAs explain why there is still interest in developing host targeting agents (HTA) that may help overcome some of these difficulties. Specifically, targeting the entry of HCV to the cell seems like a promising strategy. Recently it has been shown that the cholesterol transporter NPC1L1, a protein located in the small bowel epithelium and in the canalicular membrane of the hepatocyte is also an HCV receptor. Just as this protein is key in the entero-hepatic cycle of cholesterol, we hypothesize that there is an entero-hepatic cycle of HCV that could be disrupted by blocking NPC1L1 with ezetimibe, an already approved and readily available safe drug. Ezetimibe, either alone or in combination with DAAs, could decrease relapse rates, reduce resistance and even make treatments cheaper.

Serum cytokeratin-18 fragment levels as noninvasive marker of nonalcoholic steatohepatitis in the chilean population. / Fragmento sérico de citoqueratina-18 como marcador no invasivo de esteatohepatitis no alcohólica en población chilena.

Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH. OBJECTIVE: To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population. METHODS: Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt's criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman's rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test. RESULTS: The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61). CONCLUSION: CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.

Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Liver transplantation for hepatocellular carcinoma: evaluation of the alpha-fetoprotein model in a multicenter cohort from Latin America.

BACKGROUND & AIMS: The French alpha-fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort. METHODS: Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement (NRI) method. RESULTS: Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio (HR) of 3.15 (P = 0.0001) and lower patient survival (HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence (HR 2.2, P = 0.12) and lower survival rate (HR 2.25, P = 0.03). A comparative analysis between HBV and non-HBV patients showed that the AFP model performed better in non-HBV patients. CONCLUSIONS: The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV.

Evaluación de docentes clínicos de Postgrado: desarrollo y propiedades psicométricas del instrumento MEDUC-PG14 / Development of MEDUC-PG14 survey to assess postgraduate teaching in medical specialties

Background: Feedback is one of the most important tools to improve teaching in medical education. Aim: To develop an instrument to assess the performance of clinical postgraduate teachers in medical specialties. Material and Methods: A qualitative methodology consisting in interviews and focus-groups followed by a quantitative methodology to generate consensus, was employed. After generating the instrument, psychometric tests were performed to assess the construct validity (factor analysis) and reliability (Cronbach’s alpha). Results: Experts in medical education, teachers and residents of a medical school participated in interviews and focus groups. With this information, 26 categories (79 items) were proposed and reduced to 14 items (Likert scale 1-5) by an expert’s Delphi panel, generating the MEDUC-PG14 survey, which was answered by 123 residents from different programs of medical specialties. Construct validity was carried out. Factor analysis showed three domains: Teaching and evaluation, respectful behavior towards patients and health care team, and providing feedback. The global score was 4.46 ± 0.94 (89% of the maximum). One teachers’ strength, as evaluated by their residents was “respectful behavior” with 4.85 ± 0.42 (97% of the maximum). “Providing feedback” obtained 4.09 ± 1.0 points (81.8% of the maximum). MEDUC-PG14 survey had a Cronbach’s alpha coefficient of 0.947. Conclusions: MEDUC-PG14 survey is a useful and reliable guide for teacher evaluation in medical specialty programs. Also provides feedback to improve educational skills of postgraduate clinical teachers.

HIV through the looking glass: insights derived from Hepatitis B.

BACKGROUND: Although higher levels of hepatitis B virus (HBV) replication in HIV-HBV co-infection may relate to liver disease progression, this has not been completely elucidated. We used expression of hepatitis B core antigen (HBcAg) in liver biopsies from HIV-HBV co-infected and HBV mono-infected patients as a marker for HBV replication, and related these findings to clinical and histological parameters. METHODS: Data from 244 HBV patients were compared with 34 HIV-HBV patients. Liver biopsies were scored for inflammation, fibrosis, HBcAg, and hepatitis B surface antigen. Univariate and multivariate analyses were performed. RESULTS: HBcAg, but not hepatitis B surface antigen, staining was stronger in HIV co-infected than in HBV mono-infected. Co-infected and HBV mono-infected had similar alanine aminotransferase, inflammatory and fibrosis scores, and hepatitis B e antigen status. HBcAg staining correlated with HIV after correcting for HBV DNA and hepatitis B e antigen. CD4 counts and HIV RNA level did not correlate with intensity of HBcAg staining. HBV DNA levels were higher in HIV co-infected and correlated with HBcAg staining. CONCLUSIONS: By looking at HBcAg as a reflection of HBV replication in HIV-HBV co-infected with controlled HIV, our findings suggest that these patients may have subtle immune function defects, which could lead to adverse liver disease outcomes.

Management of nonalcoholic fatty liver disease: an evidence-based clinical practice review.

AIM: To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease (NAFLD) in clinical practice. METHODS: NAFLD has now reached epidemic proportions worldwide. The optimal treatment for NAFLD has not been established due to a lack of evidence-based recommendations. An expert panel of members of the Chilean Gastroenterological Society and the Chilean Hepatology Association conducted a structured analysis of the current literature on NAFLD therapy. The quality of the evidence and the level of recommendations supporting each statement were assessed according to the recommendations of the United States Preventive Services Task Force. A modified three-round Delphi technique was used to reach a consensus among the experts. RESULTS: A group of thirteen experts was established. The survey included 17 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 93.8% in the first round and 100% in the second and third rounds. The final recommendations support the indication of lifestyle changes, including diet and exercise, for all patients with NAFLD. Proven pharmacological therapies include only vitamin E and pioglitazone, which can be used in nondiabetic patients with biopsy-proven nonalcoholic steatohepatitis (the progressive form of NAFLD), although the long-term safety and efficacy of these therapies have not yet been established. CONCLUSION: Current NAFLD management is rapidly evolving, and new pathophysiology-based therapies are expected to be introduced in the near future. All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease, diabetes and cardiovascular events.