Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study.

INTRODUCTION: The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. PATIENTS AND METHODS: This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. RESULTS: One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001). CONCLUSIONS: Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

Abstract Introduction The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. Patients and methods This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. Results One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p< 0.001). Conclusions Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study.

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

Aminotransferase-to-platelet ratio index and Fibrosis-4 index score predict hepatic fibrosis evaluated by transient hepatic elastography in hepatitis C virus-infected hemodialysis patients.

OBJECTIVE: This study aimed to evaluate the performance of aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 index (FIB-4) in chronic kidney disease stage 5D HCV-infected patients compared to transient hepatic elastography (TE) as the gold standard. METHODS: Hemodialysis HCV-infected patients submitted to TE (FibroScan, Echosens, Paris, France) had APRI and FIB-4 calculated. Based on the best area under receiver operating characteristic curve (AUROC) for significant fibrosis and cirrhosis, APRI and FIB-4 cutoffs were determined and their performances were compared. RESULTS: Seventy patients were included. Both APRI and FIB-4 showed good performance for identifying significant fibrosis [AUROC = 0.73, 95% confidence interval (CI) 0.61-0.83 and 0.79, 95% CI 0.68-0.88; P < 0.05] and cirrhosis [AUROC = 0.82, 95% CI 0.71-0.90 and 0.85, 95% CI 0.75-0.93; P < 0.05]. APRI ≤ 0.25 excluded significant fibrosis with negative predictive value (NPV) of 81.8% and APRI > 0.61 confirmed it with a positive predictive value (PPV) of 81.8%. Similarly, NPV for FIB-4 ≤ 0.60 regarding significant fibrosis was 90.9%. NPV for cirrhosis for APRI ≤ 0.42 or FIB-4 ≤ 1.40 was 97%. However, APRI > 0.73 or FIB-4 > 2.22 showed a modest PPV of 60 and 70% to confirm cirrhosis, respectively. CONCLUSION: APRI and FIB-4 are simple, non-expensive scoring systems with good accuracy to assess fibrosis in HCV-infected hemodialysis patients, mainly excluding both significant fibrosis or cirrhosis and may be an alternative to TE in the evaluation of this population.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

2-D Shear Wave Elastography for the Evaluation of Liver Fibrosis in Hepatosplenic Schistosomiasis: Reliability of a Single Measurement and Inter-Hepatic Lobe Variability.

Data on liver and spleen stiffness by 2-D shear wave elastography (2-D SWE) in hepatosplenic schistosomiasis (HES) remain scarce. We aimed to assess the correlation between single to multiple measurements of liver and spleen stiffness and to evaluate inter-hepatic lobe variability of liver stiffness measurement (LSM) using 2-D SWE in HES patients. Liver and spleen elastography were performed in HES patients in this cross-sectional study. A total of four stiffness measurements were performed in the right lobe (RL), left lobe (LL), and spleen. The correlation between the first measurement and the median of four measurements was assessed. Liver stiffness measurement of both hepatic lobes was compared. Twenty-six HES patients were included. Liver stiffness measurement was higher in the left than in the right hepatic lobe (17.9 kPa [11.3-92.0] versus 14.9 kPa [5.6-44.4]; P = 0.019). The first measurement was similar to the median of the four measurements for the RL (14.6 [5.6-60.8] versus 14.9 kPa [5.6-44.4]; P = 0.87), LL (17.4 [8.0-128.1] versus 17.9 kPa [11.3-92.0]; P = 0.54), and spleen (50.5 [10.0-157.0] versus 55.7 kPa [19.1-119.4]; P = 0.48). An excellent correlation between the first measurement and the median of four measurements for the RL (r = 0.93; P < 0.001), LL (r = 0.88; P < 0.001), and spleen (r = 0.89; P < 0.001) was observed. In HES, LSM of the LL seems to be higher than that of the right hepatic lobe. Considering the excellent correlation between the first measurement and the median of four measurements in both hepatic lobes and spleen, a single measurement would be sufficient to evaluate liver and splenic stiffness in patients with HES.

The performance of M and XL probes of FibroScan for the diagnosis of steatosis and fibrosis on a Brazilian nonalcoholic fatty liver disease cohort.

OBJECTIVES: Recently, controlled attenuation parameter (CAP) was incorporated for XL probe. However, its performance through M and XL probes has been scarcely evaluated in nonalcoholic fatty liver disease (NAFLD). The performance of probes regarding transient elastography by Fibroscan is still under debate. AIM: Compare the performance of CAP and transient elastography in NAFLD patients obtained through XL with M probes using histological analysis as gold standard. METHODS: NAFLD patients underwent liver biopsy and FibroScan/CAP with M and XL probes the same day. C-statistic evaluated CAP performance in the identification of moderate/severe (≥33%) and severe (≥66%) steatosis by both probes and transient elastography performance for identification of significant fibrosis (≥F2). RESULTS: Eighty-one patients (74% female; age 54.2 ± 9.9 years; BMI 32.8 ± 5.2/ BMI ≥ 25 92.6%; 96% metabolic syndrome; 60% diabetes mellitus) were included. Mean CAP with M and XL probes was 314 ± 39 and 325 ± 47 dB/m, respectively. The areas under receiver operating characteristic curves (AUROCs) of the M and XL probes for steatosis detection ≥33% were 0.75 (0.64-0.84) and 0.76 (0.65-0.84) (P = 0.95) and for steatosis ≥66% 0.83 (0.73-0.90) and 0.82 (0.71-0.89) (P = 0.73), respectively, with similar performances for both degrees of steatosis. Regarding transient elastography, AUROCs of M and XL probes for ≥F2 were 0.82 (0.71-0.93) and 0.80 (0.69-0.92) (P = 0.66). CONCLUSION: Performance of M and XL probes is similar for the diagnosis of moderate and severe steatosis and significant fibrosis even on a overweight population with NAFLD.

Organ dysfunction in cirrhosis: a mechanism involving the microcirculation.

INTRODUCTION: Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. PATIENTS AND METHODS: We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan-Meier analysis was carried out. RESULTS: Fifty-four patients and 18 controls were included. Inflammatory and endothelial markers increased in advanced disease. FCD was reduced and RBCA was progressively lower according to disease severity. RBCA correlated inversely with inflammatory and endothelial biomarkers, and directly with renal function. The presence of hepatic encephalopathy correlated inversely with RBCA and directly with IL-6 and endothelin-1. In multivariate analysis, RBCA was an independent factor for organ dysfunction. The area under the receiver operating chartacteristic curve for IL-6 for survival was 0.74 (0.59-0.89), P=0.05. Transplant-free survival was 97.5% for values under 5.78 ng/ml (IL-6 best cutoff) and 83.9% above 5.78 ng/ml, log-rank=0.018. Eleven patients underwent transplantation, with an overall improvement in microcirculatory function. CONCLUSION: Our results suggest a mechanism of organ damage in cirrhosis, where microcirculatory dysfunction could be correlated to inflammatory and endothelial biomarkers, and loss of multiorgan function. IL-6 seems to be an important survival marker of inflammation. Liver transplantation improved microcirculatory dysfunction, corroborating this hypothesis.

Reliability and safety of transnasal compared to conventional endoscopy for detecting oesophageal varices in cirrhotic patients.

BACKGROUND & AIMS: Unsedated transnasal endoscopy may be used for detecting oesophageal varices. However, few studies evaluated feasibility and accuracy of this technique. We aimed to evaluate accuracy, interobserver agreement and safety of the transnasal ultrathin compared to conventional endoscopy in patients with cirrhosis. METHODS: This cross-sectional study included consecutive patients referred for screening or surveillance of oesophageal varices. Patients underwent unsedated transnasal and sedated conventional endoscopies at the same day, which were recorded in a digital video file and randomly analysed by two double-blinded endoscopists. High-risk varices were defined by the presence of large calibre or red wale marks. Accuracy, interobserver agreement and safety of transnasal were compared to conventional endoscopy. RESULTS: One hundred and thirty-three cirrhotic patients (48% male, aged of 60 ± 5, 34% Child-Pugh B/C and 71% of cases for variceal screening) were included in the study. The prevalence of oesophageal varices and high-risk oesophageal varices were 59% (n = 79) and 29% (n = 39) respectively. For the presence of oesophageal varices, transnasal GIE yielded sensitivity of 94% [95% Confidence Interval, CI 88-99], specificity of 89% [81-97] as well as positive and negative predictive value of 93% and 91% respectively. A satisfactory interobserver agreement was observed for the presence of oesophageal varices (κ = 0.89) and high-risk varices (κ = 0.65). No serious adverse events were recorded; transnasal GIE was safe and significantly associated with lower rates of hypoxaemia (P < .0001) and hypotension (P < .0001) compared to conventional endoscopy. CONCLUSIONS: Unsedated transnasal endoscopy was safe and had an excellent accuracy and high interobserver agreement for detecting oesophageal varices and for identifying high-risk varices in cirrhotic patients.

Latent Class Analysis of Noninvasive Methods and Liver Biopsy in Chronic Hepatitis C: An Approach without a Gold Standard.

AIMS: To evaluate the applicability of the Latent Class Analysis (LCA) and accuracy of transient elastography (TE), aspartate-to-platelet-ratio-index (APRI), enhanced liver fibrosis (ELF), and liver biopsy (LB) for liver fibrosis assessment in a model without a gold standard. METHODS: Significant fibrosis was defined as TE ≥ 7.1 kPa, APRI ≥ 1.5, ELF ≥ 9.37, or LB METAVIR F ≥ 2. Cirrhosis was defined as TE ≥ 12.5 kPa, APRI ≥ 2.0, ELF ≥ 10.31, or LB as METAVIR F = 4. RESULTS: 117 patients with chronic hepatitis C were included. In the LCA, for significant fibrosis the sensitivities and specificities (95% CI) were 0.92 (0.86-0.98) and 0.79 (0.72-0.86) for TE; 0.47 (0.40-0.54) and 0.99 (0.95-1.00) for APRI; 0.81 (0.74-0.88) and 0.78 (0.71-0.85) for ELF; and 0.86 (0.68-1.00) and 0.91 (0.79-1.00) for LB. For cirrhosis, the sensitivities and specificities were 0.92 (0.76-1.00) and 0.94 (0.91-0.97) for TE; 0.57 (0.37-0.77) and 0.97 (0.93-1.00) for APRI; 0.94 (0.84-1.00) and 0.88 (0.82-0.94) for ELF; and 0.30 (0.12-0.48) and 1.00 for LB. CONCLUSION: LCA was useful to evaluate accuracy of methods for liver fibrosis staging. Sensitivities and specificities of noninvasive methods were increased in LCA compared to the use of LB as the gold standard.

Burden of Chronic Viral Hepatitis and Liver Cirrhosis in Brazil - the Brazilian Global Burden of Disease Study.

INTRODUCTION AND AIM: Data on epidemiology of liver diseases in Brazil is scarce. This study aimed to estimate the burden of chronic viral hepatitis and liver cirrhosis in the country. MATERIALS AND METHODS: The indicator used was disability-adjusted life year (DALY), a sum of years of life lost due to premature mortality (YLL) and years lived with disability (YLD). Liver cirrhosis was analyzed in etiologic categories and cirrhosis of viral origin was considered part of the burden of chronic hepatitis. RESULTS: There were 57,380 DALYs (30.3 per 100,000 inhabitants) attributable to chronic hepatitis B and cirrhosis due to hepatitis B, with 41,262 DALYs in men. Most burden was caused by YLL (47,015 or 24.8/100,000) rather than YLD (10,365 or 5.5/100,000). Chronic hepatitis C and cirrhosis due to hepatitis C were responsible for 207,747 DALYs (109.6/100,000), of which 137,922 were YLL (72.7/100,000) and 69,825 (36.8/100,000) were YLD, with a higher proportion of DALYs in men (73.9%). Cirrhosis due to alcohol or other causes had a total of 536,169 DALYs (1,4% of total DALYs in Brazil), with 418,272 YLL (341,140 in men) and 117,897 YLD (97,965 in men). Highest DALYs' rates occurred at ages 60-69 in chronic hepatitis and at ages 45-59 in cirrhosis due to alcohol or other causes. CONCLUSION: Chronic viral hepatitis and liver cirrhosis are responsible for a significant burden in Brazil, affecting mainly men and individuals still in their productive years. Most burden is related to non-viral causes of cirrhosis, with a major contribution of alcohol.

Transient elastography evaluation of hepatic and spleen stiffness in patients with hepatosplenic schistosomiasis.

BACKGROUND: Hepatosplenic schistosomiasis (HES) has not been evaluated by transient elastography so far and its correlation with ultrasound variables remains to be defined. AIMS: The aim of this study was to describe the parameters of liver and spleen stiffness in HES assessed by transient elastography in comparison with cirrhotics and controls evaluating its correlation with ultrasonographic data. PATIENTS AND METHODS: HES, hepatitis C virus-cirrhotic, and control patients were included in this sectional study. Liver and spleen stiffness were compared among the three groups. The ultrasonographic parameters were compared with transient elastography in HES patients. RESULTS: Thirty HES, 30 hepatitis C virus-cirrhotic patients, and 17 controls were included. Those with HES presented liver stiffness that was significantly higher than the controls and lower than the cirrhotics: 9.7 (3.6-75.0) versus 3.7 (2.8-5.4) versus 27.0 (14.7-61.5) kPa (P<0.001). Spleen stiffness values were comparable between hepatosplenic and cirrhotics: 66.4 (25.7-75.0) versus 69.1 (18.0-75.0) kPa (P=0.78) and were significantly higher than the controls 16.5 kPa (6.3-34.3) (P<0.001). In patients with HES, high spleen stiffness was associated with right liver lobe diameter (P=0.015), splenic artery resistance index (P=0.002), portal vein diameter (P=0.021), portal vein area (P=0.008), portal vein congestion index (P=0.035), splenic vein diameter (P=0.013), and spleen diameter (P=0.021). CONCLUSION: Liver stiffness may be a useful tool to differentiate portal hypertension related to cirrhosis from that of HES. High spleen stiffness is a potential surrogate marker of portal hypertension in this population.

Intermediate fibrosis staging in hepatitis C: a problem not overcome by optimal samples or pathologists' expertise.

BACKGROUND AND AIMS: The prediction of intermediate stage of fibrosis in chronic hepatitis C represents a prognostic factor for disease progression. Studies evaluating biopsy performance in intermediate stage considering current patterns of liver samples and pathologists' variability are scarce. We aimed to evaluate the effect of optimal liver specimens (≥ 20 mm and/or ≥ 11 portal tracts) and pathologists' expertise on agreement for intermediate stage of fibrosis in chronic hepatitis C. MATERIAL AND METHODS: Guided biopsies with large TruCut needle were initially scored by four pathologists with different expertise in liver disease and posteriorly reviewed by a reference hepatopathologist to evaluate fibrosis agreement. RESULTS: Of the 255 biopsies initially selected, 240 met the criteria of an optimal fragment (mean length 24 ± 5 mm; 16 ± 6 portal tracts) and were considered for analysis. The overall agreement among all fibrosis stages was 77% (κ = 0.66); intraobserver and interobserver agreement was, respectively, 97% (k = 0.96) and 73% (κ = 0.60). Excluded samples (< 20 mm and < 11 portal tracts) presented a lower agreement (40%; κ = 0.24). Stratifying fibrosis stages, an interobserver agreement of 42% was found in intermediate stage (F2), ranging from 0 to 56% according to pathologists' expertise, compared to 97% in mild (F0-F1) and 72% in advanced fibrosis (≥ F3) (p < 0.001). Of the 23% misclassified cases, fibrosis understaging occurred in 82% of specimens, predominantly in F2, even when evaluated by a hepatopathologist. CONCLUSIONS: Liver biopsy presents intrinsic limitations to assess intermediate stage of fibrosis not overcome by optimal samples and experienced pathologists' analysis, and should not be considered the gold standard method to evaluate intermediate fibrosis in chronic hepatitis C.

Prevalence, variability, and outcomes in portal hypertensive colopathy: a study in patients with cirrhosis and paired controls.

BACKGROUND: Management of portal hypertensive colopathy (PHC) has been challenged by controversial results in its prevalence and clinical relevance. OBJECTIVE: To describe the PHC prevalence and to evaluate the variability in diagnosis, the relation to severity of liver disease, and the incidence of severe outcomes. DESIGN: Cross-sectional study. SETTING: Endoscopic unit of a tertiary-care academic center in Rio de Janeiro, Brazil. PATIENTS: Patients with cirrhosis with portal hypertension and controls paired for age and sex. INTERVENTIONS: All patients were submitted to standard and image-enhanced colonoscopies, which were recorded in a coded video file and analyzed twice by a blinded endoscopist. MAIN OUTCOME MEASUREMENTS: The prevalence of PHC. RESULTS: A total of 51 patients with cirrhosis (55% male, mean age 59 years) and 51 healthy controls (43% male, mean age 61 years) were included. The top ranking colonoscopic findings were angiodysplasia-like lesions, nonspecific vascular pattern, red spots, and colorectal varices, all significantly more frequent in patients with cirrhosis compared with controls. PHC prevalence was 71% in patients with cirrhosis. For PHC, interobserver and intraobserver agreement (k values [standard error]) were 0.68 (0.09) and 0.63 (0.10), respectively. Intraobserver agreement for colonoscopic findings was satisfactory. PHC was not related to more severe liver disease or liver stiffness. Only 5 patients developed severe outcomes during follow-up. LIMITATIONS: The exclusion of patients with cirrhosis without esophageal varices and the absence of an interobserver agreement analysis by double-blinded endoscopists. CONCLUSION: PHC was highly prevalent in patients with cirrhosis, and its diagnostic agreement was satisfactory. PHC is not associated with relevant severe outcomes in a 12-month follow-up.

Interobserver variability in transient elastography analysis of patients with chronic hepatitis C.

BACKGROUND & AIMS: Transient elastography based on liver stiffness measurement is a non-invasive method to assess hepatic fibrosis. However, interobserver variability has led to controversy over its use in fibrosis evaluation. To evaluate the interobserver variation in transient elastography in chronic hepatitis C. METHODS: We performed a cross-sectional study, analysing findings from two experienced operators who each assessed 195 patients by transient elastography on the same day. Liver stiffness measurement used to define fibrosis stages, based on METAVIR score, was: <7.1 as F0F1, 7.1-9.4 as F2, 9.5-12.4, as F3 and >12.4 kPa as F4. We also assessed interobserver variation in identification of potential oesophageal varices screening based on transient elastography. RESULTS: The interobserver intraclass correlation coefficient was 0.940 (95% CI 0.863-0.967) and measurements made by operators correlated [Spearman's ρ = 0.924; P < 0.001]. However, the median liver stiffness measurement assessed by first operators was higher (11.5 vs 9.8 kPa; P < 0.001). The discordance between operators was 35% for at least one stage of fibrosis and 5% for two or more stages. Interobserver reliability values were κ = 0.61 for fibrosis stages F ≥ 2 and κ = 0.80 for cirrhosis. Among the 74 patients determined to have cirrhosis by at least one operator, there was considerable discordance in identification of those with indication for oesophageal varices screening (κ values from 0.13 to 0.61) according to several cut-offs. CONCLUSION: Although a high correlation of liver stiffness measurement between operators, interobserver variability in transient elastography was not negligible. This method should not be used as the only screening tool for oesophageal varices in chronic hepatitis C.

Enhanced liver fibrosis panel as a predictor of liver fibrosis in chronic hepatitis C patients.

BACKGROUND: Evaluation of fibrosis is crucial in the assessment of chronic hepatitis C (CHC). The enhanced liver fibrosis (ELF) is a serological panel including hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and amino-terminal propeptide of type III procollagen (PIIINP) that has shown good results in predicting liver fibrosis in distinct scenarios of chronic liver diseases. AIMS: We aimed to assess the performance of ELF on the detection of fibrosis and cirrhosis in a CHC patient cohort and to compare the results of ELF and transient elastography (TE-Fibroscan) using liver biopsy as reference. PATIENTS AND METHODS: One hundred twenty patients were prospectively evaluated by TE and ELF using an ADVIA Centaur automated system. The ELF score was calculated using the manufacturer's algorithm. Biopsies were classified according to the METAVIR score. Receiver operator characteristic curve analyses were performed to evaluate the accuracy of ELF and TE. RESULTS: The area under the receiver operator characteristic curve (AUROC) of ELF for the diagnosis of significant fibrosis was 0.81 [95% confidence interval (CI), 0.73-0.87], for advanced fibrosis was 0.82 (95% CI, 0.74-0.88), and for cirrhosis was 0.78 (95% CI, 0.70-0.85). Using the proposed cutoffs, ELF overestimated fibrosis in 66% (81/120) of cases and underestimated in 3% (3/120). We found no statistically significant difference when comparing the AUROC of ELF and TE for diagnosing fibrosis or cirrhosis. CONCLUSIONS: ELF panel is a good noninvasive fibrosis marker and showed similar results to TE in CHC patients. However, new cutoff points need to be established to improve its performance on patients with CHC.

Genetic variability of hepatitis B and C viruses in Brazilian patients with and without hepatocellular carcinoma.

Most cases of hepatocellular carcinoma (HCC) are due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection worldwide. The aim of this study was to determine the viral genotypes and frequency of 17 mutations (15 for HBV and 2 for HCV), described previously as able to influence the course of chronic liver disease, in patients with and without HCC. This transversal study included 157 Brazilian patients with chronic hepatitis B (n = 51) and C (n = 106). Of these, 12 and 40 patients had HBV- and HCV-related HCC, respectively. Nucleotide sequencing of core promoter, pre-core, and pre-S/S regions of HBV and core region of HCV strains was performed to determine their genotypes and the frequency of the respective mutations. Among the HBV isolates, subgenotype A1 was the most prevalent in both patients with (90%) and without (61%) HCC. Fourteen out of the 15 mutations under study, as well as five different pre-S deletions, were identified. Core promoter T1753V, A1762T, and G1764A mutations were more frequent in patients with HCC than in those without, although with no statistical difference. However, a significant correlation was observed between T1753V mutation and elevation of transaminases levels (P < 0.05). As for HCV, mutation at residue 70 in the core protein of genotype 1b strains was significantly more frequent in patients with cirrhosis (56.3%) than in those without (9.1%) (P = 0.018). The detection of some key mutations in the genomes of HBV and HCV might be helpful to predict the clinical outcome of patients with chronic liver disease.