Dolores Merino

The Use of Transient Elastometry for Assessing Liver Fibrosis in Patients with HIV and Hepatitis C Virus Coinfection

BACKGROUND Transient elastometry (TE) is accurate for detecting significant liver fibrosis and cirrhosis in hepatitis C virus (HCV)-monoinfected patients. However, this procedure has been insufficiently validated in patients with human immunodeficiency virus (HIV) and HCV coinfection. The purpose of this study was to validate reported cutoff values of TE that discriminate significant liver fibrosis and cirrhosis in HIV-HCV-coinfected subjects. METHODS Liver stiffness measurements were obtained for 169 HIV-HCV-coinfected adult patients who had undergone a liver biopsy or who had received a nonhistologic diagnosis of cirrhosis within 12 months before or after a liver stiffness measurement. Patients had received no prior therapy for HCV infection. RESULTS TE measurements ranged from 3.6 kPa to 75 kPa. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.84-0.93) for significant liver fibrosis and 0.95 (95% confidence interval, 0.92-0.99) for cirrhosis. To diagnose significant liver fibrosis, a cutoff value of 7.2 kPa was associated with a positive predictive value of 88% and a negative predictive value of 75%. Thirty-four patients (20%) were misclassified when this cutoff value was used. Thirteen (24%) of 54 patients with liver stiffness values <7.2 kPa had significant liver fibrosis detected by liver biopsy. To diagnose cirrhosis, a cutoff value of 14.6 kPa was associated with a positive predictive value of 86% and a negative predictive value of 94%. Thus, 13 patients (10%) had disease that was misclassified using this cutoff value. CONCLUSIONS We found that the diagnostic accuracy of TE was high for detecting cirrhosis and good for diagnosis of significant liver fibrosis. However, the performance of TE was low for discriminating mild fibrosis from significant liver fibrosis, which might limit the applicability of this technique in clinical practice.

Prediction of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients by simple non-invasive indexes

Background: Liver biopsy is an invasive technique with associated major complications. There is no information on the validity of five non-invasive indexes based on routinely available parameters, estimated and validated in hepatitis C virus (HCV) monoinfected patients, in human immunodeficiency virus (HIV)/HCV coinfected patients. Aim: To validate these predictive models of liver fibrosis in HIV/HCV coinfected patients. Patients: A total of 357 (90%) of 398 patients from five hospitals were investigated, who underwent liver biopsy and who had complete data to validate all of the models considered. Methods: The predictive accuracy of the indexes was tested by measuring areas under the receiver operating characteristic curves. Diagnostic accuracy was calculated by estimating sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results: The models performed better when liver biopsies ⩾15 mm were used as reference. In this setting, the Forns and Wai indexes, models aimed at discriminating significant fibrosis, showed PPV of 94% and 87%, respectively. Using these models, 27–34% of patients could benefit from exclusion of liver biopsy. If both models were applied sequentially, 41% of liver biopsies could be spared. The indexes aimed at predicting cirrhosis achieved NPV of up to 100%. However, they showed very low PPV. Conclusions: The diagnostic accuracy of these models was lower in HIV/HCV coinfected patients than in the validation studies performed in HCV monoinfected patients. However, simple fibrosis tests may render liver biopsy unnecessary in deciding anti-HCV treatment in over one third of patients with HIV infection and chronic hepatitis C.

Benefits From Sustained Virologic Response to Pegylated Interferon Plus Ribavirin in HIV/Hepatitis C Virus–Coinfected Patients With Compensated Cirrhosis

BACKGROUND The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related complications and overall mortality in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. RESULTS SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval [CI], .11-3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5-8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio [HR], 8.1; 95% CI, 1.08-61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2-7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3-7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07-61; P = .043) were independently associated with overall mortality. CONCLUSIONS The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.

Natural History of Compensated Hepatitis C Virus-Related Cirrhosis in HIV-Infected Patients

OBJECTIVE To provide information about the incidence and predictors of liver decompensation and death due to liver failure in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS Prospective cohort study of 154 HIV-HCV-coinfected patients with a new diagnosis of Child-Pugh-Turcotte (CPT) class A compensated cirrhosis. We evaluated time from diagnosis to the first liver decompensation and death from liver disease, as well as predictors of these outcomes. RESULTS Thirty-six patients (23.4%) developed liver decompensation. The incidence of liver decompensation was 6.40 cases per 100 person-years (95% confidence interval [CI], 4.18-9.38 cases per 100 person-years). Factors independently associated with liver decompensation were lack of HCV therapy (hazard ratio [HR], 3.38; 95% CI, 1.09-10.53; P = .035), baseline CD4 cell counts <or=300 cells/mm3 (HR, 2.12; 95% CI, 1.14-5.04; P = .021), CPT score 6 versus 5 (HR, 3.33; 95% CI, 1.39-7.69; P = .007), and a diagnosis of cirrhosis based on data other than biopsy or transient elastography (HR, 2.09; 95% CI, 1.05-4.16; P = .036 ). Fifteen patients (9.7%) died; 11 (73%) of these 15 died from liver disease (mortality due to liver failure, 2.44 deaths per 100 person-years; 95% CI, 1.21-4.36 deaths per 100 person-years). Hepatic encephalopathy as the first liver decompensation (HR, 20.67; 95% CI, 2.71-157.57; P = .003), baseline CD4 count <or=300/mm3 (HR, 0.24; 95% CI, 0.07-0.78; P = 0.17), and baseline CPT score 6 (HR, 4.50; 95% CI, 1.63-12.37; P = .004) were independently associated with liver-related death. CONCLUSIONS The incidence of clinical liver events in HIV-HCV-coinfected patients with CPT class A compensated cirrhosis is close to that previously reported in HCV-monoinfected patients. Lower baseline CD4 cell counts, lack of therapy against HCV, and higher CPT score are the factors related to the occurrence of clinical liver events. Minimal changes in CPT score have strong impact in the prognosis of this population.

Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis†

Our aim was to assess the predictive value of liver stiffness (LS), measured by transient elastography (TE), for clinical outcome in human immunodeficiency virus / hepatitis C virus (HIV/HCV)‐coinfected patients with compensated liver cirrhosis. This was a prospective cohort study of 239 consecutive HIV/HCV‐coinfected patients with a new diagnosis of cirrhosis, done by TE, and no previous decompensation of liver disease. The time from diagnosis to the first liver decompensation and death from liver disease, as well as the predictors of these outcomes, were evaluated. After a median (Q1‐Q3) follow‐up of 20 (9‐34) months, 31 (13%, 95% confidence interval [CI]: 9%‐17%) patients developed a decompensation. The incidence of decompensation was 6.7 cases per 100 person‐years (95% CI, 4.7‐9‐6). Fourteen (8%) out of 181 patients with a baseline LS < 40 kPa developed a decompensation versus 17 (29%) out of 58 with LS ≥ 40 kPa (P = 0.001). Factors independently associated with decompensation were Child‐Turcotte‐Pugh (CTP) class B versus A (hazard ratio [HR] 7.7; 95% CI 3.3‐18.5; P < 0.0001), log‐plasma HCV RNA load (HR 2.1; 95% CI 1.2‐3.6; P = 0.01), hepatitis B virus coinfection (HR, 10.3; 95% CI, 2.1‐50.4; P = 0.004) and baseline LS (HR 1.03; 95% CI 1.01‐1.05; P = 0.02). Fifteen (6%, 95% CI: 3.5%‐9.9%) patients died, 10 of them due to liver disease, and one underwent liver transplantation. CTP class B (HR 16.5; 95% CI 3.4‐68.2; P < 0.0001) and previous exposure to HCV therapy (HR 7.4; 95% CI 1.7‐32.4, P = 0.007) were independently associated with liver‐related death; baseline LS (HR 1.03; 95% CI 0.98‐1.07; P = 0.08) was of borderline significance. Conclusion: LS predicts the development of hepatic decompensations and liver‐related mortality in HIV/HCV‐coinfection with compensated cirrhosis and provides additional prognostic information to that provided by the CTP score. (HEPATOLOGY 2012;56:228–238)

Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone

OBJECTIVES To compare the response to hepatitis C virus (HCV) therapy among human immunodeficiency virus (HIV)/HCV co-infected patients receiving a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] backbone consisting of abacavir plus lamivudine with that observed in subjects who receive tenofovir plus lamivudine or emtricitabine. METHODS A total of 256 subjects, enrolled in a cohort of 948 HIV-infected patients who received pegylated interferon and ribavirin from October 2001 to January 2006, were included in this study. All patients were taking one protease inhibitor or one non-nucleoside reverse transcriptase inhibitor and abacavir plus lamivudine or tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone during HCV therapy. Sustained virological response (SVR) rates in both backbone groups were compared. RESULTS In an intention-to-treat analysis, 20 out of 70 (29%) individuals under abacavir and 83 out of 186 (45%) under tenofovir showed SVR (P = 0.02). N(t)RTI backbone containing tenofovir was an independent predictor of SVR in the multivariate analysis [adjusted odds ratio (95% CI), 2.6 (1.05-6.9); P = 0.03]. The association between abacavir use and lower SVR was chiefly seen in patients with plasma HCV-RNA load higher than 600 000 IU/mL and genotype 1 or 4. Among patients treated with ribavirin dose <13.2 mg/kg/day, 3 (20%) of those under abacavir versus 22 (52%) under tenofovir reached SVR (P = 0.03), whereas the rates were 31% and 38% (P = 0.4), respectively, in those receiving >/=13.2 mg/kg/day. CONCLUSIONS HIV-infected patients who receive abacavir plus lamivudine respond worse to pegylated interferon plus ribavirin than those who are given tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone, especially in those receiving lower ribavirin doses.

Liver stiffness as a predictor of esophageal varices requiring therapy in HIV/hepatitis C virus-coinfected patients with cirrhosis.

Background:Liver stiffness (LS) measured by transient elastometry is associated with portal pressure in hepatitis C virus (HCV)-monoinfected patients and could predict the presence of esophageal varices in these subjects. The aim of this study was to assess the ability of LS to predict esophageal varices requiring preventive therapy for bleeding in HIV/HCV-coinfected patients. Methods:One hundred two HIV/HCV-coinfected patients with liver cirrhosis (LS ≥ 14 kPa) underwent an upper gastrointestinal endoscopy (UGE) examination. The diagnostic performance of LS for esophageal varices requiring therapy (≥F2 or F1 with red signs or Child-Pugh-Turcotte class C) was assessed by receiver operating receptor characteristic curves. Results:Nineteen patients (19%) harbored varices requiring therapy. LS in patients with and without varices needing treatment was 48 (33-71) kPa and 32 (18-48) kPa (P = 0.004). The area under the receptor operating characteristic curve (95% confidence interval) of LS for the occurrence of varices that should be treated was 0.71 (0.60 to 0.82). There was no cutoff level of LS with good positive predictive value for the presence of varices requiring therapy, but LS of 21 kPa had a negative predictive value of 100%. Twenty-six percent of patients with LS measurement and UGE showed LS <21 KPa. Conclusions:LS is higher in HIV/HCV-coinfected patients with cirrhosis who show esophageal varices requiring therapy than in those who do not. A cutoff value of LS of 21 kPa could be useful to identify patients with very low probability of varices at risk for bleeding. UGE for screening could be spared in these patients until LS increases above 21 kPa.

Application of transient elastometry to differentiate mild from moderate to severe liver fibrosis in HIV/HCV co-infected patients.

BACKGROUND/AIMS Transient elastometry (TE) is accurate for detecting cirrhosis (F=4) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. However, this procedure is less precise to differentiate mild (F < or = 1) from moderate to severe (F > or = 2) fibrosis using the cut-off value of 7.2kPa, a level previously proposed by some authors. Because of this, we elaborated and validated cut-off values of liver stiffness (LS) to better discriminate F < or = 1 from F > or = 2 in HIV/HCV co-infected subjects to aid therapy decisions. METHODS One hundred and ninety-seven co-infected patients with liver biopsy and TE measurement, without prior therapy against HCV infection, were included. RESULTS To diagnose F < or = 2, a cut-off of 9.0kPa showed a positive predictive value of 87%. To discard F > or = 2, a cut-off of 6.0kPa showed a negative predictive value of 90%. Considering all the patients, 61 (31%) patients yielded LS values < or = 6.0kPa and 81 (41%) patients showed LS values > or = 9.0kPa. There were no severe classification errors as the NPV of L < or = S6.0kPa for F > or = 3 was 100% and the NPV LS > or = 9.0kPa for F=0 was also 100%. CONCLUSIONS The usefulness of TE can be enhanced using two different cut-off values to identify patients with F < or = 1 and F > or = 2.

Insulin resistance is associated with liver stiffness in HIV/HCV co-infected patients

Background: The factors that influence liver fibrosis progression in patients co-infected with human immunodeficiency virus/hepatitis C virus (HIV/HCV) are not completely understood. It is not known if insulin resistance (IR), a condition that promotes liver fibrosis in HCV mono-infected individuals, is one of these factors. Objective: To evaluate the association between IR and liver stiffness (LS). Design: Multicentre cross-sectional study. Patients: 330 patients co-infected with HIV/HCV. Methods: LS was assessed by transient elastography, which has shown a high accuracy to predict significant fibrosis in patients co-infected with HIV/HCV. The outcome variable of the study was LS. Patients with LS⩾9 kPa were considered as having significant fibrosis. IR was calculated using the HOMA method. Results: LS was ⩾9 kPa in 150 (45%) patients. HOMA correlated with LS (Spearman’s rho correlation coefficient, 0.37; p<0.0001). The median (Q1–Q3) HOMA in patients with LS⩾9 kPa was 3.30 (2.17–5.16) while it was 2.09 (1.37–3.22) in patients with LS <9 kPa (p<0.0001). Ninety-six (39%) individuals with a HOMA <4 and 54 (63%) with a HOMA ⩾4 showed LS⩾9 kPa (p<0.0001). Analyses after excluding patients with cirrhosis yielded similar results. After multivariate analyses, age ⩾40 years (adjusted odds ratio (AOR), 1.85; 95% confidence interval (CI), 1.03 to 3.29; p = 0.03), CD4 cell count <200 cells/ml (AOR, 3.45; 95% CI, 1.67 to 7.11; p = 0.001), hepatitis B virus co-infection (AOR, 9.25; 95% CI, 2.42 to 35.31; p = 0.001), and HOMA ⩾4 (AOR, 5.33; 95% CI, 2.70 to 10.49; p<0.0001) were the independent predictors of LS⩾9 kPa. Conclusion: IR is associated with LS in patients co-infected with HIV/HCV.

Plasmablastic lymphoma of the oral cavity and jaws.

Plasmablastic lymphoma is a recently described neoplasm arising in the oral cavity and jaws of HIV-infected patients, frequently related to Epstein-Barr virus, with a morphology and immunophenotype that can cause diagnostic difficulties to the pathologist. Although initially localized, it usually behaves aggressively. The use of highly active antiretroviral therapy in combination with chemo- and radiotherapy may provide a way of improving its prognosis.