M. Grigorescu

Spleen stiffness measurement using fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients

Background and Aim:u2002 Splenomegaly in a common finding in liver cirrhosis that should determine changes in the spleens density because of portal and splenic congestion and/or because of tissue hyperplasia and fibrosis. These changes might be quantified by elastography, so the aim of the study was to investigate whether spleen stiffness measured by transient elastography varies as liver disease progresses and whether this would be a suitable method for the noninvasive evaluation of the presence of esophageal varices.

Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with genotype 1 chronic hepatitis C†‡

The efficacy and safety of albinterferon alfa‐2b (alb‐IFN), a novel recombinant protein consisting of interferon alfa‐2b genetically fused to human albumin, was evaluated in a phase 2b, open‐label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN‐alfa treatment‐naïve patients were randomized to 48‐week treatment with peginterferon alfa (PEG‐IFNα)‐2a 180 μg one time per week (qwk), or alb‐IFN 900 or 1,200 μg once every two weeks (q2wk), or 1,200 μg once every four weeks (q4wk), administered subcutaneously, plus weight‐based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real‐time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intention‐to‐treat analysis, sustained virologic response rates were 58.5% (69/118) with alb‐IFN 900 μg q2wk, 55.5% (61/110) with 1,200 μg q2wk, and 50.9% (59/116) with 1,200 μg q4wk, and 57.9% (66/114) with PEG‐IFNα‐2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb‐IFN 900 μg q2wk, 18.2% with 1,200 μg q2wk and 12.1% with 1,200 μg q4wk, and 6.1% with PEG‐IFNα‐2a (P = 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatment‐associated missed workdays were significantly lower with alb‐IFN 900 μg q2wk versus PEG‐IFNα‐2a (1.1 versus 4.3 days; P = 0.006). Conclusion: Alb‐IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG‐IFNα‐2a. (HEPATOLOGY 2008;48:407–417.)

Albinterferon Alfa-2b Was Not Inferior to Pegylated Interferon-α in a Randomized Trial of Patients With Chronic Hepatitis C Virus Genotype 1

BACKGROUND & AIMSnThe current standard of care for patients with chronic hepatitis C virus (HCV) genotype 1 is once-weekly pegylated interferon-α (Peg-IFNα) plus daily ribavirin for 48 weeks. We evaluated the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of albumin and IFNα-2b.nnnMETHODSnIn the phase 3 ACHIEVE-1 trial, 1331 patients were assigned equally to 3 open-label, 48-week treatment groups: Peg-IFNα-2a 180 μg every week, or albIFN 900 or 1200 μg every 2 weeks administered subcutaneously, with weight-based oral ribavirin 1000-1200 mg/day. During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg because of increased pulmonary adverse events (AEs) in the 1200-μg arms of both ACHIEVE studies. Main outcome measure was sustained virologic response (SVR; undetectable serum HCV RNA at week 72).nnnRESULTSnIntention-to-treat SVR rates were 51.0% (225/441), 48.2% (213/442), and 47.3% (208/440) with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. The primary objective of showing noninferiority of albIFN 900 μg (P < .001) and 1200 μg (P = .003) vs Peg-IFNα-2a for SVR was achieved. Multivariate modeling indicated consistency of treatment effect across subgroups. Serious/severe AE rates were 23.1%, 24.0%, 28.2%; treatment discontinuation rates because of AEs were 4.1%, 10.4%, 10.0%; discontinuation rates because of respiratory AEs were 0%, 0.9%, 1.6%; with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. Hematologic abnormality rates were comparable across the Peg-IFNα-2a and albIFN 900-μg groups.nnnCONCLUSIONSnalbIFN 900 μg every 2 weeks showed comparable efficacy, with similar serious/severe AE rates, although with a higher discontinuation rate, vs Peg-IFNα-2a in patients with chronic HCV genotype 1.

Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis

INTRODUCTIONnHyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver disease and atherosclerosis.nnnAIMnOur study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT).nnnPATIENTS AND METHODSn50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed.nnnRESULTSnPatients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT.nnnCONCLUSIONnNon-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.

Impaired health-related quality of life in Romanian patients with chronic viral hepatitis before antiviral therapy.

Background and aim Chronic hepatitis is a disabling condition leading to impairment of a patients quality of life. We investigated the impact of chronic viral hepatitis on health-related quality of life. The relationship between transaminase level and score in the quality-of-life questionnaire was also investigated. Methods We studied 66 patients with chronic viral hepatitis (27 with hepatitis B, 38 with hepatitis C, 1 with hepatitis B+C; 32 men, 34 women) naive to any previous antiviral therapy. All had high levels of transaminases. Patients with chronic disease or those using drugs to modify their quality of life were discarded. The control group consisted of 36 healthy volunteers (17 men, 19 women). Both groups completed the Short Form 36 health survey, with the exception of the items concerning bodily pain. Results Significant differences between the two groups for every domain of quality of life (physical functioning, role physical, mental health, role emotional, social functioning, vitality and general health) were recorded. We found no significant correlation between the level of transaminases and any item of the health-related quality-of-life questionnaire. In hepatitis B patients, several quality-of-life scores (general health, social functioning, mental health) were better than in hepatitis C patients. Conclusions Patients with chronic viral hepatitis not receiving antiviral therapy have an impaired quality of life as estimated by the Short Form 36 health survey.

Two or more synchronous combination of noninvasive tests to increase accuracy of liver fibrosis assessement in chronic hepatitis C; results from a cohort of 446 patients.

Background The prediction of fibrosis is an essential part of the assessment and management of patients with chronic liver disease. Non-invasive tests (NITs) have a number of advantages over the traditional standard of fibrosis assessment by liver biopsy, including safety, cost-effectiveness, and widespread accessibility. Objectives The aim of this study was to determine the accuracy of certain biomarkers and transient elastography (TE) alone or in combination to predict the stage of liver fibrosis in chronic hepatitis C (CHC). Also, we examined whether the combination of certain biomarkers and TE could increase the diagnostic accuracy of liver fibrosis assessment. Patients and Method A total of 446 patients who were previously diagnosed with CHC were included in the study. In the study group, 6 blood-based scores (APRI, Forns, Fib-4, Hepascore, FibroTest, and Fibrometer) were calculated, and TE was performed to validate the stage of fibrosis, compared with liver biopsy (LB) as the standard. Results Significant fibrosis (F ≥ 2) was predicted with an AUROC of 0.727, 0.680, 0.714, 0.778, 0.688, 0.797, and 0.751 for the APRI, Forns, Fib-4, FibroTest, Hepascore, and Fibrometer scores and TE (Fibroscan), respectively. Severe fibrosis (F ≥ 3) was predicted, with AUROCs ranging between 0.705 and 0.811 for Hepascore and Fibrometer, respectively. Of the biomarkers, Fibrometer had the highest AUROC value in predicting both significant and severe fibrosis. The combination of APRI or FIB-4 with Fibrometer increased the diagnostic accuracy for significant fibrosis (from 69.07 to 82.27 for APRI, P = 0.001 and from 57.74 to 81.33, P = 0.001 for Fib-4). Combining APRI or Fib-4 with TE also increased the diagnostic accuracy (from 69.07 to 80.70%, P = 0.001 for APRI and from 57.74 to 81.33%, P = 0.001 for Fib-4) for significant fibrosis. The association that included Fibrotest was also reliable for the improvement of diagnostic accuracy. These combinations were more accurate or the assessment of severe fibrosis. Conclusions The synchronous association between a simple, inexpensive score and a complex but expensive score or TE increases the diagnostic accuracy of non-invasive methods for the assessment of liver fibrosis stage.

Non-invasive ménage à trois for the prediction of high-risk varices: stepwise algorithm using lok score, liver and spleen stiffness

Liver stiffness (LS), spleen stiffness (SS) and serum markers have been proposed to non‐invasively assess portal hypertension or oesophageal varices (EV) in cirrhotic patients. We aimed to evaluate the performance of a stepwise algorithm that combines Lok score with LS and SS for diagnosing high‐risk EV (HREV) and to compare it with other already‐validated non‐invasive methods.

FibroSURE™ and FibroScan® in relation to treatment response in chronic hepatitis C virus

AIMnTo compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus (HCV) cohort.nnnMETHODSnPatients with chronic HCV were randomized to receive interferon-based therapy for 24 (genotypes 2/3) or 48 (genotype 1) wk. FibroSURE™ (FS) was assessed at baseline and at week-12 post-treatment follow-up. Baseline biopsy for METAVIR was assessed by a single pathologist. FibroScan(®) transient elastography (TE) was performed during treatment in a patient subset.nnnRESULTSnTwo thousand and sixty patients (n = 253 in Asia) were classified as METAVIR F0-1 (n = 1682) or F2-4 (n = 378). For F2-4, FS (n = 2055) had sensitivity and specificity of 0.87 and 0.61, respectively, with area under the receiver-operating curve of 0.82; corresponding values for TE (n = 214) and combined FS/TE (n = 209) were 0.77, 0.88 and 0.88, and 0.93, 0.68 and 0.88. Overall FS/TE agreement for F2-4 was 71% (κ = 0.41) and higher in Asians vs non-Asians (κ = 0.86 vs 0.35; P < 0.001). Combined FS/TE had 97% accuracy in Asians (n = 33). Baseline FS (0.38 vs 0.51, P < 0.001) and TE (8.0 kPa vs 11.9 kPa, P = 0.006) scores were lower in patients with sustained virological response than in nonresponders, and were maintained through follow-up.nnnCONCLUSIONnFS and TE may reliably differentiate mild from moderate-advanced disease, with a potential for high diagnostic accuracy in Asians with chronic HCV.

Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension

BACKGROUNDnThe diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established.nnnAIMSnTo assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices.nnnMETHODSn202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created.nnnRESULTSnThe best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness (C-statistics=0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy>80%), but were not statistically superior to liver stiffness alone.nnnCONCLUSIONSnLiver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone.

Non-invasive steatosis assessment in NASH through the computerized processing of ultrasound images: Attenuation versus textural parameters

Ultrasonography is a simple method in diagnosing nonalcoholic steatohepatitis (NASH), providing useful information, but it is subjective and does not accurately differentiate between steatosis grades. The computerized processing of the data that comprises the ultrasonic image (CPU) might transform ultra-sonography into an objective examination. CPU can be achieved either by methods based on the study of parenchymal echogenicity and on the attenuation of the ultrasounds (attenuation and back-scattering coefficients), or by methods based on the quantification of some textural parameters. In the present paper we set out to compare the performance of the attenuation coefficient (AC) and the textural parameters derived from the GLCM matrix 96 NASH patients and 24 healthy subjects were prospectively included in this study. We found a strong correlation between the AC and steatosis and a weak, but statistically significant one, with balooning and lobular inflammation, but not with fibrosis. The multivariate analysis showed, however, that only steatosis influences independently the AC. Of the analyzed textural parameters, only the GLCM entropy correlated weakly, but significantly, with the steatosis degree. Our study proves that the use of the attentuation coefficient computed on the ultrasonographic image can help differentiate healthy from NASH patients, as well as discriminate between various degrees of fatty load. The attenuation coefficient performs better than the textural parameters derived from the GLCM matrix. However, only GLCM entropy, of all textural parameters tested, correlates with steatosis, and even then, only for the differentiation normal vs NASH, not between steatosis grades.