Impairment In Chronic Hepatitis Research Articles

MON-175 Glycemic Impairment in Chronic Hepatitis C: Does the Virus Reduce B-Cell Function? An Amazonic Brazilian Study

In the course of chronic hepatitis C, extrahepatic manifestations are frequent, with important glycemic alterations, occurring approximately three times more than in the general population. In order to study this glycemic impairment in patients with Hepatitis C virus (HCV), we developed a cross-sectional and observational study with 72 patients living in State of Pará, Amazon region of Brazil, which has an endemic prevalence of HCV infection, both sexes, over 40 years of age, with a history of chronic infection by HCV and without co-infection with the Hepatitis B virus or HIV. The glycemic variables evaluated were fasting glycemia, glycemia after 2 hours of overload with glucose, insulin, HbA1c, HOMA-B and HOMA-IR, relating them to aspects of liver disease. The fibrosis grade was estimated by the FIB-4 value (FIB-4 ≥ 3.25 vs < 3.25). Of the total of 72 participants, 52.8% were women. The mean age was 61.5 ± 8.4 years. Glycemic alterations were found in 40% of the patients: 26.4% were diabetic and 13.6% with pre-diabetes. The main genotype was type 1 (78%), followed by type 3 (22%). The glycemic variables behaved in a similar way among the genotypes. When we evaluated the glycemic profile according to the degree of fibrosis, patients with higher fibrosis (n=17) presented a double prevalence of Diabetes Mellitus (41% vs 22%; p=0.51) and higher 2h glycemia (9.5 ± 4.5 mmol/L vs 6.8 ± 2.9 mmol/L, p=0.028), however and in a contrary way than expected, caused by a lower HOMA-B (111.7 ± 63.4 vs 192.8 ± 182.4; p=0.009), with equal levels of HOMA-IR, and without association with metabolic syndrome or obesity. Diabetic patients (n=19) showed a tendency for a worse response to treatment: virological sustained response (SVR) was achieved in 80% of diabetics (vs 92.3% in non-diabetics, p>0.05), especially those with genotype 3, that only 66% achieved SVR. Cirrhotic patients presented no more glycemic alterations than non-cirrhotic patients, however, diabetics showed a higher frequency of hepatocarcinoma compared to non-diabetics (10.5% vs 1.9%, p>0.05). We conclued that the frequency of glycemic changes was high in the studied population, but without association with the traditional components of the metabolic syndrome and obesity. It is suggested, therefore, that HCV infection may compromise insulin secretion and that patients diagnosed with DM may require specific treatment because they present a poorer response to antiviral treatment and have greater chronic complications of the disease.

Brain magnetic resonance spectroscopy and cognitive impairment in chronic hepatitis C patients

BackgroundCognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection may appear long before the development of severe liver cirrhosis. These alterations are not ascribed to hepatic encephalopathy; however, early detection is always difficult.ObjectiveThe aim of this study was to assess the changes of magnetic resonance spectroscopy (MRS) metabolites among chronic hepatitis C virus patients with and without cognitive impairment.Patients and methodsA cross-sectional study was conducted in Suez Canal University Hospital. Forty-six HCV patients was included and divided into two groups: patients with and without cognitive impairment. Assessment of cognitive function was done using mini-mental state examination and Wechsler Memory Scale - Revised. Both groups were subjected to single-voxel MRS to evaluate metabolites in three brain regions: the basal ganglia, hippocampus, and posterior cingulate gyrus.ResultsThe CHO/Cr was significantly higher, and NAA/Cr was significantly lower in group with cognitive impairment in the basal ganglia and posterior cingulate gyrus. Mini-mental state score had negative significant correlation with PCR of HCV. Mini-mental state score had significant negative and positive correlation with CHO/Cr and NAA/Cr, respectively, in the basal ganglia. All values of the Wechsler Memory Scale were statistically higher in the group without cognitive impairment except verbal memory score.ConclusionThere were changes at brain metabolites associated with cognitive impairment in chronic hepatitis C patients regarding a decrease of NAA/Cr ratio and an increase of CHO/Cr ratio at the basal ganglia.

Event-related evoked potential versus clinical tests in assessment of subclinical cognitive impairment in chronic hepatitis C virus

ContextChronic infection by hepatitis C virus causes impairment in neurocognitive function in up to 50% of patients which may not be detected by clinical tests.AimEarly detection of neurocognitive impairment in chronic hepatitis C patients and investigating the cognitive function in HCV patient by p300 and clinical test.Materials and methodsThe study included 60 patients with chronic hepatitis C and 30 healthy controls. Participants were subjected to a biochemical, hematological assessment, mini-mental state examination, Montreal Cognitive Assessment, P300, polymerase chain reaction (PCR), and fibroscan made for hepatitis C patients.ResultsThe digit span, attention, concentration, and memory were significantly lower in patients than controls. The delayed P300 peak latency and the reduction of its amplitude were significantly evident in patients with liver fibrosis than the controls and patients without fibrosis. These abnormalities were significantly higher with increasing the grade of fibrosis. All patients with cognitive impairment (reduced mini-mental state score) had abnormal P300-evoked responses. P300 could detect neurocognitive impairment in some patients with normal neurocognitive functions by clinical test. P300 had sensitivity (100%), specificity (59.26), positive predictive value (75%), negative predictive value (100%), and accuracy (81.67) in the detection of neurocognitive impairment in HCV patient.ConclusionPatients with chronic hepatitis C infection had significant impairment in their cognitive functions. This impairment increases with the increase in grade of hepatic fibrosis. P300 can detect minimal and subclinical impairment of cognitive function at early stages of chronic hepatitis with accuracy (81.67).Trial registrationPACTR on 19 march 2018 retrospectively. Identification number for the registry is PACTR201804003215168.

Renal Impairment in Chronic Hepatitis B: A Review.

The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver and is involved in liver diseases. Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. Nucleos(t)ide analog (NA) therapy effectively suppresses HBV replication by inhibiting HBV polymerase, thus decreasing the levels of serum HBV-DNA and delaying the progression of cirrhosis. Although NA therapy is recommended for all patients with chronic HBV infection, regardless of the level of renal dysfunction, there is limited information on NA use in patients with chronic kidney disease. In addition, in patients with end-stage liver cirrhosis, hepatorenal syndrome can be fatal. Hence, we should take into account the stage of impaired renal function in patients with cirrhosis. The aims of this article are to review the epidemiology, clinical presentation, treatment, and prevention of HBV-associated nephropathy.

Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV) infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127) expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

Patient health utility, work productivity, and lifestyle impairment in chronic hepatitis C patients in France

France has a high prevalence of patients with chronic hepatitis C virus (HCV). Clinical consequences of HCV are well-recognized, while health-related quality of life (HRQoL) and productivity impacts remain less understood. This study evaluates how HCV disease severity and HCV treatment outcomes impact HRQoL and productivity among patients in France. From October 2012 to January 2013, physicians treating HCV patients in France completed Patient Record Forms, which included information on patient demographics, disease stage, and treatment status. Subsequently, these HCV patients completed the EQ-5D-3L health-state instrument and the HCV-specific Work Productivity and Activity Impairment (WPAI:HepC) Questionnaire. Results are reported in descriptive and stratified analyses by disease stage and treatment status. Linear regression analyses were performed to determine independent associations between disease severity and treatment status with EQ-5D and WPAI:HepC. There were 297 matched physician and patient response forms completed. Mean EQ-5D Index score was 0.764, and mean EQ-VAS score was 65.85. Regression analyses showed that older age and worse disease severity were significantly associated with lower EQ-5D Index and EQ-VAS scores. Stratification of EQ-5D Index and EQ-VAS scores showed significantly better scores for HCV treatment responders compared to non-responders. Stratification of WPAI:HepC questions by disease stage revealed greater productivity impact on HCV patients with more severe disease. In a cross-sectional sample of HCV patients in France, worsening HRQoL and productivity/activity impairment was significantly associated with disease progression and increasing age. This information provides insight into the benefits of treating HCV patients and preventing disease progression.

P24: Health‐Related Quality of Life and productivity impairment in chronic hepatitis C patients in Germany

Journal of Viral HepatitisVolume 21, Issue s2 p. 34-35 Poster SessionFree Access P24: Health-Related Quality of Life and productivity impairment in chronic hepatitis C patients in Germany First published: 08 October 2014 https://doi.org/10.1111/jvh.12333_23AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issues2Special Issue: Abstracts for the Viral Hepatitis Congress 2014, 9–11 October 2014, Frankfurt, GermanyOctober 2014Pages 34-35 RelatedInformation

Clinical study of adefovir dipivoxil in renal impairment

To elucidate the incidence of renal impairment in chronic hepatitis B (CHB) patients on adefovir dipivoxil (ADV). We retrospectively enrolled 127 CHB patients on ADV alone (38.6%) or in combination with lamivudine (61.4%) for over 12 months.Renal function was measured by estimated glomerular filtration rate (eGFR). And renal dysfunction was defined as mild ( 50%). During a treatment duration of 12 months, 2 patients (1.6%) developed mild renal impairment.At Month 36, there were 13 patients with renal damage (10.4%) and one case of hypertension with severe renal impairment plus bone pain.The characteristic of renal pathology was tubule injury.Modification of dosing interval or discontinuation of ADV may arrest a further decline of eGFR in CHB patients. Key words: Nucleotides; Nephrosis

Are you concerned about your fatigue? Fatigue perceptions mediate the relationship between insomnia and fatigue related functional impairment in chronic hepatitis C infection

Insomnia affects about one third of patients with chronic hepatitis C infection. Fatigue is the cardinal daytime symptom of insomnia. Those with comorbid insomnia are the most fatigued patients at liver clinics. Although we have successful treatments for insomnia, fatigue is a frequent residual complaint. This is especially concerning since chronic fatigue is associated with significant functional impairment in this group. Understanding the psychological mechanisms that maintain fatigue and fatigue related functional impairment in those with a history of co-morbid insomnia may facilitate the development of CBT-I treatments enhanced with a fatigue treatment component in the medically ill. Treatment seeking participants with chronic hepatitis C infection ( N = 115; 36% females; mean age = 56) were enrolled in a mixed design study on fatigue. Participants completed questionnaires on their fatigue, sleep, fatigue specific cognitions, depression and anxiety. Medical data were retrieved from hospital charts. Fatigue was assessed with the Fatigue Severity Scale (FSS), insomnia was assessed with the Insomnia Severity Index (ISI). The Brief Illness Perception Questionnaire, the Chronic Fatigue Acceptance Questionnaire and the Daytime Insomnia Symptom Response Scale were used for measuring fatigue specific cognitive factors. A bootstrapping mediation analysis (confidence level: 5000 resamples) revealed that the effect of insomnia on fatigue was fully mediated by two domains of fatigue perception: concern about fatigue (standardized effect = .3759, bias corrected accelerated confidence interval = .2444 to .5127) and control over fatigue (standardized effect = .0891, bias corrected accelerated confidence interval = .0290 to .1968). Patients’ concern about their fatigue and their perceived degree of control over their fatigue provided the link between insomnia (ISI) and fatigue related functional impairment (FSS). Future research should test this theoretical model in other medically ill populations with comorbid insomnia and significant fatigue. The model implies that a fatigue-focused component targeting fatigue perceptions and fatigue management may become an important addition to the insomnia treatment in the medically ill.

Frequency and risk factors of renal impairment during long‐term adefovir dipivoxil treatment in chronic hepatitis B patients

There are insufficient data on renal safety during long-term adefovir dipivoxil (ADV) treatment. We aimed to elucidate the incidence and risk factors of renal impairment in chronic hepatitis B (CHB) patients treated with ADV. We retrospectively enrolled 687 CHB patients (51.4% with compensated cirrhosis) treated with ADV alone (18.2%) or in combination with lamivudine (81.8%) for more than 12 months. Renal function was measured using the estimated glomerular filtration rate (eGFR), and renal dysfunction was defined as mild (20-30% decrease), moderate (30-50%), or severe (more than 50%). During the median treatment duration of 27 months, 72 patients (10.5%) developed renal impairment, which was mild in 77.8% of cases, moderate in 20.8% of cases, and severe in one patient. The cumulative incidence of renal impairment at 1, 3, and 5 years was 2.6%, 14.8%, and 34.7%, respectively. Modification of the dosing interval or discontinuation of ADV was required in seven and three patients, respectively, and none of them showed a further decline in the eGFR. Although a univariate analysis revealed age, the number of exposure to radio-contrast dye, liver cirrhosis, and hepatocellular carcinoma as risk factors of renal impairment, age was the only significant risk factor identified in the multivariate analysis (odds ratio = 1.048, 95% confidence interval = 1.019-1.076, P = 0.001). Renal impairment in long-term ADV users was relatively frequent, but serious renal toxicity was rare, and all cases were safely managed. Careful monitoring of renal function is required, especially in older patients.

Hyaluronic acid and aspartate aminotransferase levels normalized by liver function can reflect sinusoidal impairment in chronic liver disease

To evaluate the relationship between hyaluronic acid/aminopyrine breath test (HA/ABT) ratio and fibrosis score in chronic hepatitis, and between HA/ABT and clinical staging (child-turcotte-pugh'score, CTP; and model for end stage liver disease, MELD) in cirrhosis, as well as to evaluate the aspartate aminotransferase (AST)/ABT in relation to the HA/ABT. We studied 48 patients with histologically proven chronic hepatitis C (CHC) and 35 patients with compensated cirrhosis (CIR). HA/ABT and AST/ABT showed a more significant correlation with the fibrosis score than HA or ABT or AST alone in the 48 CHC patients: r=0.568 (P<0.0001), r=0.610 (P<0.0001), r=0.450 (P=0.0021), r=-0.449 (P=0.0021), and r=0.472(P=0.0012), respectively. Progressive liver damage (fibrosis 1-2 vs fibrosis 3-6 vs cirrhosis) was significantly (P<0.05) reflected by both HA/ABT (mean+/-SEM: 4.0+/-0.9 vs 18.1+/-4.2 vs 149.9+/-33.1) and AST/ABT (6.3+/-1.8 vs 12.7+/-1.6 vs 42.1+/-14.6). A strong relationship was found between HA/ABT and AST/ABT (r=0.755 P<0.0001). In cirrhotic patients, the most significant relationship was observed between HA/ABT and CTP r=0.483 and P=0.0049, and MELD r=0.523 and P=0.0023. Considering that HA levels in chronic hepatitis depend on the progressive impairment of sinusoidal endothelial cells (SEC), related to progressive fibrosis, HA/ABT ratio would seem to be the most specific reflection of progressive impairment of the SEC. AST/ABT could be used as a possible surrogate of HA in identifying SEC impairment in chronic hepatitis.

Critical role of MHC class I-related chain A and B expression on IFN-alpha-stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection.

Dendritic cells (DCs) augment effector functions of NK cells, but the underlying mechanisms are not fully understood. Here we show in an in vitro coculture system that human monocyte-derived DCs enhance IFN-gamma production, CD69 expression, and K562 cytolytic ability of NK cells when DCs are prestimulated with various maturation stimuli such as IFN-alpha or LPS. Of interest is the finding that NK cell activation mediated by LPS-stimulated DCs was dependent on IL-12 produced in DC/NK coculture, but that IFN-alpha-stimulated DC-mediated activation was not. Alternatively, MHC class I-related chain A and B (MICA/B), ligands for NKG2D activating receptor, were found to be induced on DCs upon IFN-alpha stimulation and to be responsible for the NK activation because mAb-mediated masking of MICA/B as well as inhibition of direct cell-to-cell contact using transwell insert completely abolished DC-dependent NK cell activation by IFN-alpha. Finally, DCs recovered from chronic hepatitis C virus-infected patients showed defects in the induction of MICA/B and impaired ability to activate NK cells in response to IFN-alpha stimulation. These findings suggested that MICA/B induction on DCs may be one of the mechanisms by which IFN-alpha activates NK cells; this impairment might affect IFN-alpha responsiveness in hepatitis C virus infection.