Background and purpose
Neurological manifestations have been identified in the context of autoimmune hepatitis (AIH). Previous case reports highlighted the association between AIH and sensory ...neuronopathy (SN). Despite that, little is known about the frequency of AIH‐related SN and its clinical/neurophysiological profile. Moreover, it is not clear whether SN is an AIH‐specific manifestation or related to chronic liver damage.
Methods
Seventy consecutive AIH patients were enrolled and their characteristics were compared with 52 consecutive patients with chronic active hepatitis B. All subjects underwent clinical and neurophysiological evaluation. Further comparisons were performed between AIH SN and AIH non‐SN patients.
Results
Mean ages and male:female proportions in the AIH and chronic active hepatitis B groups were 42.2 ± 16.3/51.7 ± 13.6 years and 14:56/29:23, respectively. The frequencies of carpal tunnel syndrome, radiculopathy and polyneuropathy were similar between groups. In contrast, SN was identified only in AIH patients (5/70 vs. 0/52, P = 0.04); the overall prevalence of AIH‐related SN was 7% with an average profile of a woman in her 40s with asymmetric onset of sensory deficits that chronically evolved to disabling proprioceptive ataxia associated with marked dysautonomia. Neurological disability and hepatocellular damage did not follow in parallel. Anti‐fibroblast growth factor receptor type 3 antibodies were found in 3/5 (60%) of the patients with AIH‐related SN. Clinical or demographic predictors of SN in the context of AIH could not be identified.
Conclusion
Sensory neuronopathy, but not other peripheral nervous system diseases, is a specific AIH neurological manifestation. It is often disabling and, in contrast to hepatocellular injury, does not respond to immunosuppression.
Summary
Vibration‐controlled transient elastography (VCTE) is widely used for noninvasive fibrosis staging in chronic hepatitis C. However, internal validation is based solely on variability and ...success rate and lacks reproducible quality indicators. We analysed the graphic representation of shear wave propagation in comparison with morphometric results of liver biopsy, eliminating observer variability bias. Individual elastograms were classified according to two morphologic criteria: extension of wave propagation (length of the graphic representation) and shear wave dispersal (level of parallelism displayed in the elastogram). Then, a score based on these criteria stratified the elastogram in classes I through III (highest to lowest technical quality). Liver stiffness results of each measurement were compared with collagen contents in liver biopsy by morphometric analysis. A total of 3243 elastograms were studied (316 patients). Digital morphometry in liver biopsy showed significant fibrosis in 66% of samples and advanced fibrosis in 31%. Elastogram quality analysis resulted in 1438 class I measurements (44%), 1070 class II (34%) and 735 class III. Area under the receiver operating curve (AUROC) for severe fibrosis according to class (I, II and III) was 0.941, 0.887 and 0.766, respectively. For advanced fibrosis, AUROCs were 0.977, 0.883 and 0.781, respectively. Spearman's correlation testing for all classes and levels of fibrosis demonstrated significant independent association (r2 = −.95, P < .01). Our study is the first to propose measurable quality criteria for VTCE and to validate them against objective assessment of liver biopsy through digital morphometric imaging analysis. We concluded that VCTE performance is significantly influenced by quality assessment of individual measurements. Considering these criteria in clinical practice may improve accuracy.
BACKGROUND AND OBJECTIVEControlled attenuation parameter (CAP) diagnostic performance for steatosis grading has been controversial and considerable observer-related variability in liver biopsy has ...been reported. This is a subanalysis of a larger chronic hepatitis C study on noninvasive fibrosis staging.
MATERIALS AND METHODSPatients were prospectively enrolled for paired liver biopsy and transient elastography. Biopsy fragments were subjected to digital morphometric steatosis quantification. Associated patient and technical factors, including a newly described elastogram quality score, were evaluated.
RESULTSA total of 312 patients were included in the final analysis. The mean liver stiffness was 8.7±2.1 kPa. Morphometry showed S0 in 19.2% of patients, S1 in 28.5%, S2 in 31.1%, and S3 in 21.2%. CAP showed S0 in 11.2% of patients, S1 in 26.6%, S2 in 56.7%, and S3 in 5.4%. Spearman coefficient showed a positive and independent correlation between CAP and morphometric analysis (r=0.48, P<0.05), except for distinguishing S1 and S2 (P=0.11). Area under the receiver operating characteristic curves for the presence or absence of steatosis was 0.944; differentiation between levels I, II, and III were 0.776, 0.812, and 0.879. Elastogram quality independently predicted accuracy odds ratio (OR)6.95, 95% confidence interval (95%CI)4.45–9.06 as well as CAP interquartile range OR2.81, 95%CI1.67–3.99 and liver stiffness (OR0.78, 95%CI0.51–0.80).
CONCLUSIONWe present an external validation for CAP against the objective steatosis quantification provided by digital morphometry. Fairly good performance indicators were found, except for S1 versus S2 differentiation. Variability and higher liver stiffness were associated with lower performance. Achieving higher quality measurements, however, overcame such limitations with excellent accuracy.
Knowledge of HBV genotype is very important for clinical treatment. Studies have suggested possible pathogenic and therapeutic differences among HBV genotypes. The aim of this study was to determine ...HBV subtypes and genotypes in HBV-infected patients in our region (southeast Brazil) and to correlate results with clinical and histopathological data.
One hundred and thirty-nine HBsAg-positive patients were included in the study. All patients were anti-HCV and anti-HIV negative (64% male; mean age 42 +/- 14.5 years; range 7-80 years; 84% Caucasian) and were followed up at the University Hospital. A method for genotyping and subtyping HBV by partial HBsAg gene sequencing with primers common to all known genotypes was used. The viral load was measured by Amplicor Monitor assay (Roche).
HBV genotype A was the most prevalent (55%), while genotypes C, D and F were found in 3%, 38% and 4% of HBV-infected patients, respectively. Among the patients infected by genotype A, 18.3% (14/76) were African descendents and, among the patients infected by genotype D, 11.3% (6/53) were also African descendents. In the four patients infected with genotype C, 2 were Asian descendents and 2 were Caucasians. All (7) genotype F infected patients were Caucasians. Seventy percent of our HBsAg-positive patients were HBeAg negative (62% genotypes A; 26.2% D; 7.1% C and 4.7%F). The viral load of HBV-DNA was about 5 times higher in HBeAg-positive than in HBeAg-negative patients. About 40% of these patients had alanine aminotransferase of up to 1.5 times the normal level. The mean stage of fibrosis in genotype A patients (2.8) was significantly higher than the mean stage of fibrosis in genotype D patients (2.0) (P = 0.0179).
The genotypes encountered in our HBV-infected patients were apparently a consequence of the types of immigration that occurred in our region, where European and African descendents predominate. The HBeAg-negative status predominated, possibly due to the length of time of infection. The viral load in HBeAg-positive patients was higher than in HBeAg-negative individuals. The fibrosis grade in genotype A-infected patients was more advanced than genotype D-infected patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIMThe aim of this study was to determine risk factors for premature treatment discontinuation among patients with hepatitis C and advanced fibrosis with advanced fibrosis treated with interferon ...(IFN)-free direct antiviral agents (DAA)-based therapy.
PATIENTS AND METHODSWe included all patients with chronic hepatitis C virus infection and advanced liver fibrosis in whom treatment was initiated with IFN-free DAA therapy at a university hospital from December 2015 through June 2016. We prospectively collected data from medical records using standardized questionnaires and evaluated them using Epi Info 7.1.2.0. The primary outcome was treatment interruption and associated factors.
RESULTSIn total, 214 patients were included in this study; 180 patients were treated with sofosbuvir (SOF)+daclatasvir±ribavirin (RBV), 31 received SOF+simeprevir±RBV, and three were treated with SOF+RBV. Treatment discontinuation rate was 8.9% (19 patients) and cirrhotic decompensation was the main reason 8 (42.1%). Among patients with Child B or C cirrhosis (31), 10 (32.2%) prematurely interrupted treatment. The risk factors for treatment discontinuation in univariate analysis were older age (P=0.0252), higher comorbidity index (P=0.0078), higher model for end-stage liver disease (P<0.0001), higher fibrosis index based on the 4 factores (P=0.0122), and lower hemoglobin (P=0.0185) at baseline. Multivariate analysis showed that older age (odds ratio1.1, 95% confidence interval1.02–1.19) and higher model for end-stage liver disease (odds ratio1.27, 95% confidence interval1.03–1.56) were associated with premature treatment interruption.
CONCLUSIONOlder age and advanced liver disease were related to treatment interruption. Identification of risk factors associated with treatment discontinuation is important to recognize patients who should be followed up closely during treatment, ando those whom possibly may not benefit from immediate DAA treatment or should be followed up closely during treatment.
Acrylic polymers were extensively used in past restoration practices, usually as consolidants or protecting agents. Their removal is often required because polymer coatings can improve some decay ...processes of stone substrates and, after ageing, may generate undesirable materials on the surface of artifacts. Therefore, the removal of old polymer coating from the surface of artifacts has become a common operation in the conservation of cultural heritage. As with other cleaning operations, it is a delicate process that may irreversibly damage the artifacts if not correctly carried out. The main aim of this study was to determine the appropriate cleaning procedure for efficiently removing old acrylic polymers (e.g., Paraloid B-72) from the surface of historical buildings. For this purpose, a polymer was applied to two different porous stone substrates (bio-calcarenite and arenaria stone). The hydrogel cleaning approach was used for the present study, as preliminary results suggested that it is the most promising polymer-removing method. The considered hydrogel (based on a semi-interpenetrating polymer network involving poly(2-hydroxyethyl methacrylate) and polyvinylpyrrolidone) was prepared and characterized using different techniques in order to assess the gel’s properties, including the gel content, equilibrium water content, retention capability, hardness, Young’s modulus, and morphology. After that, the hydrogel was loaded with appropriate amounts of nano-structured emulsions (NSEs) containing a surfactant (EcoSufTM), organic solvents, and H2O, then applied onto the coated surfaces. Moreover, plain EcoSurfTM in a water emulsion (EcoSurf/H2O) was also used to understand the polymer-removing behavior of the surfactant without any organic solvent. A comparative study was carried out on artificially aged and unaged polymer-coated samples to better understand the cleaning effectiveness of the considered emulsions for removing decayed polymer coatings. The experimental results showed that the NSE-loaded hydrogel cleaning method was more effective than other common cleaning procedures (e.g., cellulose pulp method). In fact, only one cleaning step was enough to remove the polymeric material from the stone surfaces without affecting their original properties.
Morbidity and mortality rate in equine anesthesia is still unacceptably high. Thus it is critical contemplating whether the benefit of general anesthesia for a specific patient and procedure ...outweighs the risks. Sedative protocols that would allow performing diagnostic and surgical procedures with the patient remaining standing would therefore be ideal. Infusion of short-acting agents allows to rapidly achieve a titratable steady state of sedation. Supplementing sedatives and tranquilizers with systemic analgesic or regional anesthetic techniques (i.e. epidurals) facilitates standing surgical procedures. Multimodal analgesia would also provide superior analgesia with potentially fewer side effects than a single agent approach.
WHIRLY2 is a single‐stranded DNA binding protein associated with mitochondrial nucleoids. In the why 2‐1 mutant of Arabidopsis thaliana, a major proportion of leaf mitochondria has an aberrant ...structure characterized by disorganized nucleoids, reduced abundance of cristae, and a low matrix density despite the fact that the macroscopic phenotype during vegetative growth is not different from wild type. These features coincide with an impairment of the functionality and dynamics of mitochondria that have been characterized in detail in wild‐type and why 2‐1 mutant cell cultures. In contrast to the development of the vegetative parts, seed germination is compromised in the why 2‐1 mutant. In line with that, the expression level of why 2 in seeds of wild‐type plants is higher than that of why 3, whereas in adult plant no difference is found. Intriguingly, in early stages of shoots development of the why 2‐1 mutant, although not in seeds, the expression level of why 3 is enhanced. These results suggest that WHIRLY3 is a potential candidate to compensate for the lack of WHIRLY2 in the why 2‐1 mutant. Such compensation is possible only if the two proteins are localized in the same organelle. Indeed, in organello protein transport experiments using intact mitochondria and chloroplasts revealed that WHIRLY3 can be dually targeted into both, chloroplasts and mitochondria. Together, these data indicate that the alterations of mitochondria nucleoids are tightly linked to alterations of mitochondria morphology and functionality. This is even more evident in those phases of plant life when mitochondrial activity is particularly high, such as seed germination. Moreover, our results indicate that the differential expression of why 2 and why 3 predetermines the functional replacement of WHIRLY2 by WHIRLY3, which is restricted though to the vegetative parts of the plant.
More than 50% of hepatitis C viruses (HCV)-infected patients do not respond to the classical Interferon (IFN)/Ribavirin (RBV) combination therapy. The aim of this study was to evaluate the efficacy ...of retreatment with Peg-Interferon alpha-2b (PEG-IFN alpha-2b) plus RBV, in patients with HCV, genotypes 1 or 3, who were non-responders to the previous standard treatment with IFN/RBV.
In the period 2005-2007, a total of 238 HCV chronic patients were non-responders to previous treatment with IFN plus RBV. Of these 130 agreed to be retreated with PEG-IFN alpha-2b and participated in this evaluation (90 with genotype 1 HCV and 40 with genotype 3 HCV). Patients were retreated at assisted IFN application hubs in compliance with the country's public health system rules. They received subcutaneous PEG-IFN alpha-2b, 1.5 microg, once weekly, associated with RBV, through the oral route, with doses determined according to weight (1,000 mg if weight <or= 75 kg and 1,250 mg if > 75 kg). Patients with genotype 1 HCV were retreated for over 48 weeks and patients with genotype 3 HCV for over 24 weeks. HCV-RNA was tested by polymerase chain reaction (PCR) at baseline, at week 12, at the end of the treatment, and 6 months thereafter. The predictiveness of week 12 in the development of a sustained virologic response (SVR) was also evaluated. Patients with negative HCV-RNA at week 12 were considered as early virologic responders (EVR).
EVR was observed in 25% of the patients with genotype 1 HCV and in 64% of the patients genotype 3 HCV (risk = 2.075 and p-value = 0.0414). SVR was observed in 22.2% of the patients with genotype 1 HCV and in 40% with genotype 3 HCV (intention-to-treat analysis). The positive predictive value (PPV) of the HCV-RNA testing at week 12, in order to obtain the SVR, was 65% for genotype 1 and 56% for genotype 3, and the negative predictive value (NPV) was 88% for genotype 1 and 89% for genotype 3.
PEG-IFN alpha-2b plus weight-based ribavirin is effective in re-treating previous interferon-alpha plus RBV failure; 22.2% of the patients with genotype 1 HCV and 40% of patients with genotype 3 HCV achieved SVR.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous reports suggest cryoglobulinemia might influence the hepatitis C virus (HCV) infection clinical course and treatment response but this association has not been thoroughly evaluated. We aimed ...to assess the relationship between cryoglobulinemia and sustained viral response (SVR) in patients treated for HCV infection. We included patients with HCV infection treated from January 2003 through December 2006. Biochemical analyses, detection cryoglobulinemia, and liver biopsies were performed prior to treatment. Genotype 1 or 4 infections received Peg‐interferon (IFN) alpha‐2a or ‐2b for 48 weeks; genotypes 2 or 3 received IFN alpha for 24 weeks. All patients also received ribavirin. Of 329 enrolled patients, 242 (73%) were male and the median age was 43 years. Cryoglobulinemia was detected in 196 (59.6%) patients; liver biopsy was performed in 301. Multivariate analysis showed an association of cryoglobulinemia with severe active necroinflammation (A3) (adjusted odds ratio AOR= 9.48; 95% confidence interval CI: 1.50‐59.92) and rheumatoid factor (RF) level (AOR= 1.01; 95% CI: 1.00‐1.02). Variables associated with advanced fibrosis were age, aspartate aminotransferase and alkaline phosphatase levels, alcohol use, and presence of diabetes. Variables independently associated with SVR were cryoglobulinemia (AOR= 2.33, 95% CI: 1.26‐4.32), absence of cirrhosis (AOR= 4.5, 95% CI: 1.4‐14.80), and RF level (AOR= 1.008, 95% CI: 1.001‐1.014). Our findings suggest cryoglobulinemia is associated with severe necroinflammatory activity in HCV‐infected patients. We also provide the first evidence for an association between cryoglobulinemia and higher SVR rates, highlighting its potential role as a prognostic factor for treatment response.
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