Jose Ignacio Vargas

CD4/CD8 ratio as a predictor of the response to HBV vaccination in HIV-positive patients: A prospective cohort study.

BACKGROUND Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission mechanisms and thus coinfection is frequent. Active immunization against HBV is essential in HIV patients. Reports using standard and reinforced HBV vaccination schedules vary widely in seroconversion rates depending on the characteristics of the included patients. Regional data concerning HBV vaccination in HIV patients are scarce. We aim to determine the serological response to HBV vaccination using standard schedule in HIV-positive patients and to evaluate characteristics that predict seroconversion. MATERIALS AND METHODS We performed a single centre prospective study of HBV vaccination with standard schedule in HIV-positive patients. Adults with negative markers of HBV infection were included between November 2012 and December 2014. Anti-HBs titres were measured 4-8 weeks after completion of vaccination schedule. Clinical, laboratory values and HIV characteristics were analyzed to determine their association with seroconversion and adherence to the HBV vaccination schedule. RESULTS The study included 245 HIV-positive patients, 68.9% were male and the mean age was 42.1 years. A total of 80.7% of the patients had undetectable HIV viral loads, 86.1% had CD4 counts >200, and 94.7% were on HAART. The response to vaccination was positive in 62% (95% CI, 56-68%) and mean anti-HBs titres of 646 IU/ml. 85.5% of the responders had anti-HBs titres >100 IU/ml. An age less than 45 years, no tobacco use and a CD4/CD8 ratio >0.4 were associated with seroconversion in multivariate analysis. The seroconversion rates were 86% in the subgroup of patients who met these criteria. A total of 97.9% of the study population completed the vaccination schedule. CONCLUSION The CD4/CD8 ratio was the primary factor associated with positive serological conversion in the multivariate analysis. The seroconversion rates were higher in a selected group of patients who were particularly suitable for the use of the standard HBV vaccination schedule.

Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

HBV‐HIV coinfection is prevalent. Frequently, anti‐HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti‐HBs reactivity; or present as “isolated anti‐HBc,” related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV‐positive individuals. Regional data about this condition are scarce. Anti‐HBc rapid test has been used as screening, but its performance has not been described in HIV‐positive patients. The aim of this study was determine prevalence of anti‐HBc in HIV‐positive patients, serological pattern of HBV resolved infection and isolated anti‐HBc, evaluating presence of HBV occult infection. Assess anti‐HBc rapid test compared to ECLIA. Methods included measurement of anti‐HBc and anti‐HBs in HIV‐positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to “isolated anti‐HBc” individuals. Detection of anti‐HBc by rapid test and ECLIA. In 192 patients, prevalence of anti‐HBc was 42.7% (82/192); associated to male gender, drug use, men‐sex‐men, positive‐VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti‐HBs, mean titers of 637 ui/ml. Isolated anti‐HBc in 8.3% (16/192), associated to detectable HIV viral load and no‐use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti‐HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti‐HBc in HIV‐positive individuals is high, in most cases accompanied with anti‐HBs as HBV resolved infection. Low prevalence of “isolated anti‐HBc,” with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti‐HBc rapid test cannot be recommended as screening method for anti‐HBc. J. Med. Virol. 88:639–646, 2016.

Sublingual tacrolimus administration provides similar drug exposure to per-oral route employing lower doses in liver transplantation: a pilot study

Per‐oral tacrolimus administration is not always practicable. Sublingual administration is a potential alternative, but its feasibility and effectiveness compared with oral route has not been established.

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

Purpose of reviewThe purpose of this study is to analyze the current evidence regarding the use of statins in patients with chronic liver disease and cirrhosis.Recent findingsChronic liver disease (CLD), cirrhosis, and its complications, including hepatocellular carcinoma (HCC), are significant public health problems. The use of statins in patients with CLD has been a matter of concern, and physicians are often reluctant to its prescription in these patients. This mainly relates to the potential occurrence of drug-induced liver injury. However, newer evidence from pre-clinical and clinical research has shown that statins are drugs with a potentially beneficial impact on the natural history of cirrhosis, on portal hypertension, and in HCC prevention.SummaryIn this review, we summarize current evidence regarding the influence of statins in endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis, and their vasoprotective effects in portal hypertension; we also focus on existing data about the impact of statins in cirrhosis development, progression, and complications and critically assess the current concerns about its use in patients with CLD.

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.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. (Rev Med Chile 2017; 145: 1235-1242)

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 Brunts 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 Spearmans 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.

Hepatotoxicity in Patients with Metabolic Syndrome: Causes and Consequences

Purpose of ReviewThe purpose of this review was to analyze the current evidence regarding the incidence, mechanisms, and outcomes of drug-induced liver injury (DILI) and hepatotoxicity in patients with metabolic syndrome and nonalcoholic fatty liver disease.Recent FindingsDILI is a complex clinical entity. Although uncommon, its incidence and diagnosis have been rising in recent years as basic research and clinical databases provide information about its etiology, clinical course, and prognosis. The prevalence of metabolic syndrome and non-alcoholic fatty liver disease is on the rise in western countries. Recently, features of the metabolic syndrome have been identified as factors affecting the phenotype and evolution of DILI, both in pre-clinical and clinical research.SummaryIn the present review, we summarize current evidence regarding the influence of features of metabolic syndrome in the presentation, clinical course, and prognosis of DILI.

Letter: sublingual dosing of tacrolimus in transplant patients―interesting concept to overcome first pass effects. Authors' reply

1. Solari S, Cancino A, Wolff R, et al. Sublingual tacrolimus administration provides similar drug exposure to per-oral route employing lower doses in liver transplantation: a pilot study. Aliment Pharmacol Ther. 2017;45:1225-1231. 2. Federico S, Carrano R, Sabbatini M, et al. Sublingual administration improves systemic exposure of tacrolimus in kidney transplant recipients: comparisonwith oral administration. Eur J Clin Invest. 2016;46:651-657.

Achieving protection against HBV in HIV patients: Finding the best strategy.

ABSTRACT HBV and HIV coinfection is common and entails important morbi-mortality. Vaccination and anti-HBs seroconvertion is a desirable goal in HIV infected patients. New strategies are necessary to predict seroconversion and clinical endpoints. More studies, in the subgroup of HIV patients with poor immunovirological status are needed.