Maria Isabel Schinoni

The effect of early virological response in health-related quality of life in HCV-infected patients

Twenty‐nine HCV‐infected patients were treated with pegylated interferon alpha. Diagnosis was based on serum HCV RNA‐PCR positive results and liver biopsy. All patients had elevated serum levels of alanine aminotransferase at the time of the study, but liver disease was compensated. Patients were evaluated at baseline treatment and after 4 and 12 weeks of antiviral treatment with the Medical Outcomes Study 36‐item Short‐Form Health Survey. The Mini‐International Neuropsychiatric Interview was used to exclude previous or current psychiatric diagnoses. Both patients and psychiatrists were blind to the HCV RNA status, and serum HCV RNA test results only became available after the visit at week 12. After antiviral treatment, 16 patients (55.2%) were classified as nonresponders and 13 (44.8%) were classified as responders. When compared to nonresponders, responders had a greater improvement in the HRQOL scores for the mental health domain (Pu2009<u2009.019). Differences in other domains were not significant. The present study confirms that active viral infection is one possible reason for the poor Health‐Related Quality of Life in this population. J. Med. Virol. 80:419–423, 2008.

Incomplete septal cirrhosis: an enigmatic disease

Abstract: Incomplete septal cirrhosis is a form of macronodular cirrhosis characterized by fine and incomplete septa, which delimit rudimentary regeneration nodules. Its etiopathogeny is uncertain and is associated with various diseases such as regenerative nodular hyperplasia, idiopathic portal hypertension, and partial non‐cirrhotic nodular transformation, as well as with progression and regression of cirrhosis of any etiology. Few studies are available in the literature describing the clinical and biological characteristics of incomplete septal cirrhosis.

Anti-Golgi complex antibodies during pegylated-interferon therapy for hepatitis C.

Abstract: Background/Aim: Pegylated interferon (Peg‐IFN) plus ribavirin is the standard therapy for hepatitis C. Peg‐IFN has several antiviral mechanisms, but its role in hepatitis C treatment seems to be related to its immunomodulatory effect. Ribavirin, an antiviral agent, potentiates IFN activity when added to it. Both drugs are associated with adverse reactions of different magnitudes. Autoimmune phenomena have been reported with this treatment. In this paper, we describe cases of ALT/GGT flares during Peg‐IFN plus ribavirin treatment, which related to the appearance of anti‐Golgi antibody and disease progress.

HCV/HTLV Coinfection: Does HTLV-1 Interfere in the Natural History of HCV-Related Diseases?

Hepatitis C virus (HCV) and human T‐lymphotropic virus type 1 (HTLV‐1) coinfection occurs in many regions. However, few studies have focused on the natural history of HCV‐induced liver disease in coinfected patients. To describe the clinical, epidemiological, and histopathological aspects of HTLV‐1/HCV coinfection in Brazil. A cross‐sectional study with 23 patients coinfected with HCV/HTLV. The control groups consisted of 21 patients monoinfected with HCV and 20 patients monoinfected with HTLV‐1. The cytokine profiles (Th1 and Th2 cell responses), clinical, laboratory features, and histopathological aspects were examined. The control group for cytokine analysis validation consisted of patients monoinfected with HTLV, and a fourth group consisted of healthy blood donors. No anthropometric differences present between the three infected groups. We observed higher serum concentrations of IFN‐γ in patients coinfected with HCV/HTLV‐1 than those in HCV monoinfected patients. The HCV/HTLV‐1 coinfected group also exhibited a higher degree of liver steatosis than the HCV monoinfected patients. Results suggest that HCV/HTLV‐1 coinfection may result in a different pattern of HCV infection due to the immunologic disorders likely associated with HTLV‐1, but there is no clear evidence of the HTLV role in the natural history of HCV infection. J. Med. Virol. 88:1967–1972, 2016.

Hepatitis C Virus Infection as a Traumatic Experience

Objective The purpose of this study was to evaluate whether individuals consider their HCV infection to be a potentially traumatic experience. Additionally, we investigated its association with Post-Traumatic Stress Disorder (PTSD) and the impact of PTSD diagnosis on health-related quality of life (HRQoL) in HCV infected subjects. Methods We conducted a cross-sectional survey of 127 HCV-infected outpatients recruited at a University Hospital in Salvador, Brazil. All subjects answered an orally-administered questionnaire to gather clinical and socio-demographic data. We investigated traumatic experiences and the subjects perception of the disease using the Trauma History Questionnaire. PTSD and other psychiatric diagnoses were assessed through the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS). HRQoL was assessed using Short-Form 36 (SF-36). Results Approximately 38.6% of the patients considered hepatitis C to be a traumatic experience. Of these, 60.7% had a PTSD diagnosis. PTSD was associated with significant impairment in quality of life for individuals in seven SF-36 domains as shown bymultivariate analysis: Role-Physical (β: −24.85; 95% CI: −42.08; −7.61), Bodily Pain (β: −19.36; 95% CI: −31.28; −7.45), General Health (β: −20.79; 95% CI: −29.65; −11.92), Vitality (β: −11.92; 95% CI: −20.74; −3.1), Social Functioning (β: −34.73; 95% CI: −46.79; −22.68), Role-Emotional (β: −26.07; 95% CI: −44.61; −7.53), Mental Health (β: −17.46; 95% CI: −24.38; −10.54). Conclusion HCV is frequently a traumatic experience and it is strongly associated with PTSD diagnosis. PTSD significantly impaired HRQoL.

Adiponectin levels and insulin resistance among patients with chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is associated with insulin resistance (IR), rapid disease progression, and decreased virological response to antiviral treatment. In addition, obesity is a risk factor for chronic hepatitis C evolution and is associated with IR. As adiponectin is an adipokine that is associated with obesity and IR, this study aimed to investigate serum levels of adiponectin among patients with HCV infection and IR. Thirty-three patients with untreated HCV infection underwent testing of serum adiponectin levels (capture ELISA) and were compared to 30 healthy subjects with similar body mass indexes (BMI). Data were also obtained for several homeostatic model assessment (HOMA) indexes: HOMA-IR, HOMA-β, and HOMA-adiponectin. Patients with HCV infection had higher adiponectin levels, which predominantly were observed among women. Hyperadiponectinemia was not associated with high BMI. Patients with HCV infection had higher HOMA-IR and HOMA-β values, although no difference was observed for HOMA-adiponectin. Patients with HCV infection and overweight/obese status had higher HOMA-IR values, although no association was observed for adiponectin levels. Hyperadiponectinemia and IR were not influenced by HCV load or liver fibrosis. The predictors of IR were BMI, glycemia, and serum levels of insulin and non-high-density lipoprotein cholesterol, but not adiponectin levels. Thus, patients with chronic hepatitis C have significant metabolic alterations (hyperadiponectinemia and high HOMA-IR values) that are independent of HCV viremia and liver fibrosis. Among these patients, HOMA-IR but not HOMA-adiponectin was appropriate for diagnosing IR.

Mutations associated with drug resistance and prevalence of vaccine escape mutations in patients with chronic hepatitis B infection

The Brazilian public health system (SUS) has provided antiviral drugs for chronic hepatitis B treatment for over 10 years, but a system for monitoring for drug‐related resistance mutations is not available. Determine the presence of HBV mutations associated with resistance to nucleos(t)ide analogs among 81 patients with chronic HBV infection in Salvador—BA—Brazil. HBV‐DNA was PCR amplified with primers deduced from the rt domain at the HBV P gene, the sequence extended 1032u2009bp (from amino acid 1 to 344—rt domain). Those sequences were submitted to the HBV drug resistance database to retrieve each mutation according to the genotype. HBV genotype A1 (85.2%) was the most prevalent, followed by genotype A2 (4.9%), F (6.2%), and C1, D2, and D4 (1.2% each). Six patients (7%) exhibited resistance mutations to LAM, ETV, and TDF: two with patterns L180Mu2009+u2009M204V and four with other different patterns: L80Iu2009+u2009L180Mu2009+u2009M204I; L80Vu2009+u2009L180Mu2009+u2009M204V; M204I; A194T. All of these mutations were present in patients with genotype A (four A1 and two A2). In addition, four mutations in gene S (three cases with the sI195M mutation and one with the W196L mutation), were detected, corresponding to a rate of 6% of vaccine escape mutations. Althougth the small sample size, an association was found between the occurrence of HBV resistance mutations and HBeAg positivity, co‐infection with HIV and a history of treatment for HBV and/or HIV.

Apoptosis and progression of hepatic fibrosis in hepatitis C patients

Hepatitis C is a worldwide endemic disease, affecting roughly 200 million people. It has a variable prognosis, depending on the progression to fibrosis. During the last five years, the importance of apoptosis for the pathogenesis of various diseases, including hepatitis, has been recognized. It has been suggested that an increase in T cell-apoptosis during a hepatitis C virus infection is the cause of impaired regulation of the immune cellular response, helping to maintain infection. Thus, the interest in discovering the probable mechanisms by which the hepatitis C virus perpetuates in the liver, and to determine the conditions that predispose for progression of this disease, makes investigation of apoptosis in hepatic injury of great interest. We have made an overview of the various mechanisms by which the cell, more specifically the hepatic cell, is affected by apoptosis, and how it interacts with the hepatitis C virus and the immune system.

Genotyping of HBV and tracking of resistance mutations in treatment-naïve patients with chronic hepatitis B

Background and aims Resistance mutation analogs to nucleos(t)ides have been described in treatment-naïve patients with chronic hepatitis B (CHB), with clinical implications. The aim of this study was to investigate primary resistance mutations and genotypes circulating in patients naïve to chronic hepatitis B, in the Northern and Northeastern regions of Brazil. Methods We conducted a study of resistance mutations and genotypic characterization of hepatitis B virus (HBV) in 189 treatment-naïve patients chronically infected with HBV. Results Drug resistance-associated mutations located in the RT domain of the P gene (rtHBV) were found in 6% of the treatment-naïve patients from the Northeastern Region. The mutations were rtA194T, rtL180M + rtM204V, rtS202I, rtM204I, and rtA181S. No patient in the Northern Region had the resistance mutation. In the gene S region, the frequency of vaccine escape mutations was 2.4% in the Northeastern Region and 8.6% in the Northern Region. Conclusion This information before the start of treatment may contribute to clinical decision making, reducing treatment failure and the risk of progression to cirrhosis and hepatocellular carcinoma for CHB.

Hepatoportal sclerosis related to the use of herbals and nutritional supplements. Causality or coincidence

xa0Introduction and aim. Non-cirrhotic idiopathic portal hypertension (NCIPH), also known as hepatoportal sclerosis (HPS) is a disease of uncertain etiology. However, various pathophysiological mechanisms has been postulated, including chronic or recurrent infections and exposure to drugs or toxins. In this context, it appears to be of multifactorial etiology or resulting from a portal vascular endothelium aggression. It is important to consider whether the use of dietary supplements and herbs can trigger or contribute to the occurance of HPS. We report a possible association of HPS with the consumption of herbals and / or dietary supplements.nnnMATERIAL AND METHODSnWe describe two cases of HPS in patients without known etiology causes associated with this disease.nnnRESULTSnBoth patients were females who were diagnosed with HPS following the consumption of Herbalife® products and putative anorexigenic agents in the form herbals infusions. Image-based analysis and the assessment of the histopathological alterations found in the livers confirmed the diagnosis. The histopatological analysis of liver samples from both patients showed portal tracts enlarged by fibrosis with disappearance or reduction in the diameter of the portal vein branches. In many portal tracts, portal veins branches were replaced by aberrant thin-walled fendiforme vessels. The bile ducts and branches of the hepatic artery show normal aspects.nnnCONCLUSIONnAfter the exclusion of other etiologic factors and a comprehensive analysis of clinical history, consumption of Herbalife® products and anorexigenic agents was pointed-out as a puttative predisposing factor for the development of the disease.INTRODUCTION AND AIMnNon-cirrhotic idiopathic portal hypertension (NCIPH), also known as hepatoportal sclerosis (HPS) is a disease of uncertain etiology. However, many pathophysiological mechanisms has been postulated, including thrombophilia, chronic recurrent infections and exposure to drugs or toxins. In this context, it appears to be of multifactorial etiology or resulting from a portal vascular endothelium aggression. It is important to consider whether the use of dietary supplements and herbs can trigger or contribute to the occurance of HPS. We report a possible association of HPS with the consumption of herbal and / or dietary supplements.nnnMATERIAL AND METHODSnWe describe two cases of HPS in patients without known etiology causes associated with this disease.nnnRESULTSnBoth patients were females who were diagnosed with HPS following the consumption of Herbalife® products and putative anorexigenic agents in the herbal infusions. Image-based analysis and the assessment of the histopathological alterations found in the livers confirmed the diagnosis. The histopatological analysis of liver samples from both patients showed portal tracts enlarged by fibrosis with disappearance or reduction in the diameter of the portal vein branches. In many portal tracts, portal veins branches were replaced by aberrant thin-walled fendiforme vessels. The bile ducts and branches of the hepatic artery show normal aspects.nnnCONCLUSIONnAfter the exclusion of other etiologic factors and a comprehensive analysis of clinical history, consumption of Herbalife® products and anorexigenic agents was pointed-out as a puttative predisposing factor for the development of the disease.