Renata M. Perez

MR Imaging of Hypervascular Lesions in the Cirrhotic Liver: A Diagnostic Dilemma

Cirrhosis is characterized by a spectrum of hepatocellular nodules that mark the progression from regenerative nodules to low- and high-grade dysplastic nodules, followed by small and large hepatocellular carcinomas (HCCs). Characterization of small nodules on the basis of imaging and histopathologic findings is complicated by an overlap in findings associated with each type of nodule, a reflection of their multistep transitions. Vascularity patterns change gradually as the nodules evolve, with an increasing shift from predominantly venous to predominantly arterial perfusion. Regenerative and low-grade dysplastic nodules demonstrate predominantly portal perfusion and contrast enhancement similar to that of surrounding parenchyma. Differentiation of high-grade dysplastic nodules and well-differentiated HCCs on the basis of dynamic imaging and histologic findings is challenging, with a high rate of false-negative results. Some small nodules that lack hypervascularity may be early HCCs. Progressed small and large HCCs usually present no diagnostic difficulty because of their characteristic findings. Although characterization of hypervascular lesions in the cirrhotic liver is difficult, it is a key step in disease management and is the radiologists responsibility.

Past and current hepatitis E virus infection in renal transplant patients

The chronic course of hepatitis E virus infection in immunosuppressed patients has been recently documented; however, clinical features and factors associated with this occurrence are not well known. The aim of this study was to evaluate the prevalence of previous or current HEV infection in renal transplant patients. One hundred ninety‐two kidney transplant patients were studied and classified in three groups: G1‐infected with hepatitis B and/or C virus; G2‐patients with elevated ALT; G3‐patients with normal ALT and no hepatotropic virus infection. Demographic, epidemiologic and clinical characteristics were compared between the groups. Patients with HEV infection (previous or current) were also compared to those who tested negative for HEV. HEV infection was detected using serologic (anti‐HEV IgG) and molecular (HEV RNA) methods. Anti‐HEV IgG was positive in 28 (15%) while HEV RNA was positive in 20 (10%). When both markers were considered, 44 (23%) patients showed evidence of previous or current HEV infection. However, both markers were concomitantly positive in only four cases (2%). In the comparative analysis, patients infected with HBV and/or HCV showed lower frequency of anti‐HEV IgG (P = 0.009). There was no difference regarding demographic, epidemiologic and laboratory variable between viremic and non‐viremic patients. In conclusion, past and current infection with HEV was a frequent finding among renal transplant recipients. Actively infected patients (HEV RNA positive) did not present distinct demographic and epidemiological characteristics or laboratory alterations suggestive of underlying liver damage. Therefore, infection with HEV can only be detected in immunosuppressed patients by systematic investigation of HEV RNA. J. Med. Virol. 86:948–953, 2014.

A single nucleotide polymorphism, rs129679860, in the IL28B locus is associated with the viral kinetics and a sustained virological response in a chronic, monoinfected hepatitis C virus genotype-1 Brazilian population treated with pegylated interferon-ribavirin

Single nucleotide polymorphisms (SNPs) in the interleukin (IL)28B locus have been associated with a sustained virological response (SVR) in interferon-ribavirin (IFN-RBV)-treated chronic hepatitis C virus (HCV)-infected patients in European and African populations. In this study, the genotype frequency of two IL28B SNPs (rs129679860 and rs8099917) in a cohort of chronic HCV-monoinfected patients in Brazil was evaluated and the SNP sufficient to predict the treatment response outcome was determined. A total of 66 naïve genotype-1 chronic HCV-infected patients were genotyped and the associated viral kinetics and SVR were assessed. The overall SVR was 38%. Both the viral kinetics and SVR were associated with rs129679860 genotypes (CC = 62% vs. CT = 33% vs. TT = 18%, p = 0.016). However, rs8099917 genotypes were only associated with SVR (TT = 53% vs. TG = 33% vs. GG = 18%; p = 0.032). In this population, the analysis of a single SNP, rs12979860, successfully predicts SVR in the IFN-RBV treatment of HCV.

Hepatitis C among Predialysis Patients: Prevalence and Characteristics in a Large Cohort of Patients

Background: The factors associated with hepatitis C virus (HCV) infection in predialysis patients need to be better investigated. The aims of this study were to evaluate the prevalence, risk factors, clinical, biochemical and virological characteristics of chronic HCV infection in predialysis patients. Methods: Anti-HCV antibodies were determined in a large cohort of predialysis patients. Epidemiological and laboratorial characteristics of HCV infection were evaluated in predialysis patients and this group was matched to a control group consisting of predialysis patients without viral infection (1:3) and compared in terms of risk factors and alanine aminotransferase (ALT) levels. Logistic regression analysis was applied to identify variables independently associated with chronic HCV infection. Results: A total of 1,041 patients (61% males) with a mean age of 61 ± 15 years and mean creatinine clearance of 36 ± 18 ml/min were included. Forty-one (3.9%) patients were anti-HCV positive and, of these, 39 (95%) presented viremia. Predialysis patients with HCV more frequently showed a history of blood transfusion before 1992 (66.7 vs. 10.3%; p < 0.001) and major surgeries (53.8 vs. 17.1%; p < 0.001), a higher proportion of undetermined etiology of kidney disease (43.6 vs. 17.1%; p = 0.001), and higher ALT levels (1.3 vs. 0.4 ×ULN; p < 0.001). History of blood transfusion before 1992 (p < 0.001; OR: 19), intravenous drug abuse (p = 0.002; OR: 69) and ALT levels (p < 0.001; OR: 50) were the variables that were independently associated with chronic HCV infection. The accuracy of ALT in detecting HCV infection was 92%. The most prevalent HCV genotype was 1b (48.7%) and 56.5% of patients presented high HCV viral load. Conclusion: Chronic HCV infection among predialysis patients is related to increased parenteral exposure. Elevated ALT levels suggest the need for HCV screening as part of the predialysis care since ALT seems to be a good marker of this infection.

Is alanine aminotransferase a good marker of histologic hepatic damage in renal transplant patients with hepatitis C virus infection

Abstract:  Introduction:  Renal transplant (RTx) patients with hepatitis C frequently show normal levels of alanine aminotransferase (ALT) and the significance of ALT in this group has not been established.

Intravoxel Incoherent Motion Diffusion Weighted MR Imaging at 3.0 T: Assessment of Steatohepatitis and Fibrosis Compared with Liver Biopsy in Type 2 Diabetic Patients.

Objective To evaluate the capability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) to assess steatohepatitis and fibrosis determined by histopathology in type 2 diabetic patients. Methods Fifty-nine type 2 diabetic patients (49 women, 10 men; mean age, 54 ± 9 years) were submitted to liver biopsy for the evaluation of non-alcoholic fatty liver disease (NAFLD) and underwent DWI on a 3.0T MR system using 10 b values. Institutional approval and patient consent were obtained. Pure molecular-based (D), perfusion-related (D*), and vascular fraction (f) were calculated using a double exponential model and least squares curve fitting. D, D*, and f were compared between patients with and without steatohepatitis and between patients with and without fibrosis. The variables were compared by using the Ranksum test and Student t-test. Results Steatohepatitis was observed in 22 patients and fibrosis in 16 patients. A lower D median (0.70 s/mm2 vs. 0.83 s/mm2, p<0.05) and a lower D* median (34.39 s/mm2 vs. 45.23 s/mm2, p<0.05) were observed among those with steatohepatitis. A lower D median (0.70 s/mm2 vs. 0.82 s/mm2, p<0.05) and a lower D* median (35.01 s/mm2 vs. 44.76 s/mm2, p=0.05) were also observed among those with fibrosis. Conclusion IVIM-DWI has the potential to aid in the characterization of steatohepatitis and fibrosis.

Is MR Spectroscopy Really the Best MR-Based Method for the Evaluation of Fatty Liver in Diabetic Patients in Clinical Practice?

Objective To investigate if magnetic resonance spectroscopy (MRS) is the best Magnetic Resonance (MR)-based method when compared to gradient-echo magnetic resonance imaging (MRI) for the detection and quantification of liver steatosis in diabetic patients in the clinical practice using liver biopsy as the reference standard, and to assess the influence of steatohepatitis and fibrosis on liver fat quantification. Methods Institutional approval and patient consent were obtained for this prospective study. Seventy-three patients with type 2 diabetes (60 women and 13 men; mean age, 54±9 years) underwent MRI and MRS at 3.0 T. The liver fat fraction was calculated from triple- and multi-echo gradient-echo sequences, and MRS data. Liver specimens were obtained in all patients. The accuracy for liver fat detection was estimated by receiver operator characteristic (ROC) analysis, and the correlation between fat quantification by imaging and histolopathology was analyzed by Spearmans correlation coefficients. Results The prevalence of hepatic steatosis was 92%. All gradient-echo MRI and MRS findings strongly correlated with biopsy findings (triple-echo, rho = 0.819; multi-echo, rho = 0.773; MRS, rho = 0.767). Areas under the ROC curves to detect mild, moderate, and severe steatosis were: triple-echo sequences, 0.961, 0.975, and 0.962; multi-echo sequences, 0.878, 0.979, and 0.961; and MRS, 0.981, 0.980, and 0.954. The thresholds for mild, moderate, and severe steatosis were: triple-echo sequences, 4.09, 9.34, and 12.34, multi-echo sequences, 7.53, 11.75, and 15.08, and MRS, 1.71, 11.69, and 14.91. Quantification was not significantly influenced by steatohepatitis or fibrosis. Conclusions Liver fat quantification by MR methods strongly correlates with histopathology. Due to the wide availability and easier post-processing, gradient-echo sequences may represent the best imaging method for the detection and quantification of liver fat fraction in diabetic patients in the clinical practice.

An inexpensive and worldwide available digital image analysis technique for histological fibrosis quantification in chronic hepatitis C.

Hepatic fibrosis staging is based on semiquantitative scores. Digital imaging analysis (DIA) appears more accurate because fibrosis is quantified in a continuous scale. However, high cost, lack of standardization and worldwide unavailability restrict its use in clinical practice. We developed an inexpensive and widely available DIA technique for fibrosis quantification in hepatitis C, and here, we evaluate its reproducibility and correlation with semiquantitative scores, and determine the fibrosis percentage associated with septal fibrosis and cirrhosis. 282 needle biopsies staged by Ishak and METAVIR scores were included. Images of trichrome‐stained sections were captured and processed using Adobe® Photoshop® CS3 and Adobe® Bridge® softwares. The percentage of fibrosis (fibrosis index) was determined by the ratio between the fibrosis area and the total sample area, expressed in pixels calculated in an automated way. An excellent correlation between DIA fibrosis index and Ishak and METAVIR scores was observed (Spearmans r = 0.95 and 0.92; P < 0.001, respectively). Excellent intra‐observer reproducibility was observed in a randomly chosen subset of 39 biopsies with an intraclass correlation index of 0.99 (95% CI, 0.95–0.99). The best cut‐offs associated with septal fibrosis and cirrhosis were 6% (AUROC 0.97, 95% CI, 0.95–0.99) and 27% (AUROC 1.0, 95% CI, 0.99–1), respectively. This new DIA technique had high correlation with semiquantitative scores in hepatitis C. This method is reproducible, inexpensive and available worldwide allowing its use in clinical practice. The incorporation of DIA technique provides a more complete evaluation of fibrosis adding the quantification to architectural patterns.

Acute hepatitis C in Brazil: Results of a national survey

The incidence of acute hepatitis C has decreased in the world. However, new cases are still reported. The objective of this study was to obtain data of acute hepatitis C in Brazil and to identify risk factors of transmission, diagnostic criteria, clinical presentation, evolution, and treatment. A questionnaire was sent to all members of the Brazilian Society of Hepatology. Sixteen centers participated with a total of 170 cases between 2000 and 2008. Among them, 37 had chronic renal failure on hemodialysis and were evaluated separately. The main diagnostic criterion in non‐uremic patients was ALT (alanine aminotransferase) elevation associated with risk factors. In patients with chronic renal failure, anti‐hepatitis C virus (HCV) seroconversion was the most frequent criterion. Among the 133 non‐uremic patients the main risk factors were hospital procedures, whereas in hemodialysis patients, dialysis was the single risk factor in 95% of the cases. Jaundice was more frequent in non‐uremic patients (82% vs. 13%; P < 0.001) and ALT levels were higher in these individuals (P < 0.001). Spontaneous clearance was more frequent in non‐uremic patients (51% vs. 3%; P < 0.001). Sixty‐five patients were treated: 39 non‐uremic patients and 26 on dialysis. Sustained virological response rates were 60% for non‐uremic and 58% for uremic patients (P = 0.98). There was no association of these rates with the study variables. These findings show that cases of acute hepatitis C are still occurring and have been related predominantly to hospital procedures. Measures to prevent nosocomial transmission should be adopted rigorously and followed to minimize this important source of infection observed in this survey. J. Med. Virol. 83:1738–1743, 2011.

Hepatitis C in chronic kidney disease: predialysis patients present more severe histological liver injury than hemodialysis patients?

Background: The characteristics of hepatitis C virus (HCV) infection in predialysis patients are poorly understood and they could be different from hemodialysis patients. Aims: To evaluate the demographics, laboratory and histological characteristics of chronic HCV infection in predialysis patients and to compare them with those observed in hemodialysis patients. Methods: Thirty-nine predialysis patients with chronic HCV infection were compared to HCV-infected hemodialysis patients (ratio of 1:3) in terms of demographics, laboratory and histological characteristics. The fibrosis progression rate (FPR) was calculated as the ratio between fibrosis stage and duration of infection. Results: Predialysis patients were older (57 ± 10 vs. 45 ± 12 years; p < 0.001), presented a higher proportion of elevated alanine aminotransferase (71.8 vs. 41.0%; p = 0.001) and aspartate aminotransferase (64.1 vs. 26.5%; p < 0.001), a higher proportion of interface hepatitis (66.7 vs. 47%; p = 0.033) and more advanced fibrosis (71.8 vs. 16.2%; p = 0.001). Among patients with estimated duration of infection, predialysis patients presented a longer duration of infection (22 vs. 6 years; p < 0.001) and no difference in FPR was observed between groups (p = 0.692). Conclusion: Although predialysis patients with HCV infection present more severe histological injury than hemodialysis patients, this finding probably reflects a longer duration of infection with no evidence supporting that hepatitis C presents a more aggressive course in this group.