Explore the vast range of titles available.

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications. It’s poorly understood how renal manifestations develop in HEV infection in patients. Here, the authors observe glomerular accumulation of the viral protein ORF2 in complex with host IgG in immunocompromised patients with chronic or acute HEV infection who developed glomerulonephritis.

Fatigue is the most commonly reported symptom of Hepatitis C Virus (HCV) infected patients and severely impacts their quality of life. The aim of this study was to measure the impact of 3D regimen treatment on the fatigue, daytime physical activity and sleep efficiency of HCV infected patients with fatigue. HEMATITE was an observational, prospective, open-label, single-arm, Swiss multi-centric study in mono-infected HCV genotype 1 patients. The 28 week observation period comprised of 4 weeks preparation, 12 weeks treatment and 12 weeks follow-up. Fatigue was assessed using the fatigue severity scale (FSS) questionnaire. Patients with FSS ≥ 4 (clinically significant fatigue) were included. The activity tracker, ActiGraph GT9X Link®, was used to measure daytime physical activity and sleep efficiency. Outcome analysis was performed on a scaled down intention to treat (sdITT) population, which excluded patients with insufficient tracker data at all study visits and a modified ITT (mITT) population, which consisted of patients with complete tracker data at all study visits. Forty of 41 patients in the ITT population had a sustained virologic response 12 weeks post-treatment (SVR12). Mean baseline FSS score was 6.0 for the sdITT population and 5.9 for the mITT population and decreased from baseline to 12 weeks post-treatment by 2.6 (95% confidence interval [CI]: 2.1, 3.1) for the sdITT (n = 37) population and 2.8 (95% CI: 2.2, 3.4) for the mITT (n = 24) population. Mean daytime physical activity or sleep efficiency did not change considerably over the course of the study. Measurement by the activity tracker of mean day time physical activity did not show a considerable change from baseline to SVR12 upon treatment with 3D regimen. Nevertheless, a reduction of fatigue as assessed with the validated fatigue severity scale (FSS) was observed, suggesting a causative role of HCV in this extrahepatic manifestation. ClinicalTrials.gov identifier: NCT03002818.

Background and Aim Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy‐1, an adhesion molecule detected as soluble Thy‐1 (sThy‐1) in serum, is primarily expressed by portal myofibroblasts (PMF) and, to a lesser extent, hepatic stellate cells (HSC), serving as a marker for myofibroblast activity in liver pathology. This study aimed to elucidate the correlation between Thy‐1 expression in liver histology and sThy‐1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction‐associated steatotic liver disease (MASLD). Methods Liver histology samples were stained for Thy‐1, and sThy‐1 was measured using an enzyme‐linked immunosorbent assay (ELISA). Results In patients with PBC and MASLD, an association between portal Thy‐1 expression and the extent of fibrosis was observed. Notably, while sinusoidal Thy‐1 expression aligned with fibrosis severity in PBC (p < 0.001), this association was not statistically significant in MASLD (p = 0.059). Moreover, variations in soluble Thy‐1 levels paralleled the progression from mild to advanced fibrosis stages in PBC. Conclusions Thy‐1 expression levels were associated with the severity of fibrosis, which could support its role in monitoring the presence and activity of myofibroblasts in liver diseases.

In this small pilot sub-study, longitudinal gut microbiota composition changes, after successful treatment of hepatitis C virus (HCV) with the co-formulated glecaprevir/pibrentasvir (GLE/PIB), were analyzed before treatment (baseline) and 12 weeks post-treatment. Participating patients provided a fresh stool sample the week before their study visit, from which microbial DNA was extracted and sequenced for the 16S rRNA region in an Illumina MiSeq2 platform. Microbial and statistical analyses were conducted to determine the alpha-diversity (number of different taxa within a sample) and beta-diversity (number of overlapping taxa between samples). Stool samples from 58 patients were eligible for analysis. There were 27 patients with HCV genotype 1, 10 with genotype 2, 16 with genotype 3, and 5 with genotype 4. No statistically significant differences in gut microbiota diversity, species richness, or microbial community pattern were found at baseline and at post-treatment Week 12. Lack of statistically significant differences remained consistent in further analysis by demographic and baseline disease characteristics. Surprisingly, no statistically significant changes in alpha- and beta-diversity were seen in the microbiota after GLE/PIB treatment, though there was a trend toward less richness over time. Further investigation is needed into this unexpected outcome to better understand the role of HCV treatment and the gut microbiota.

Human alveolar echinococcosis (AE) is a zoonotic infection caused by the fox tapeworm Echinococcus ​​​​​​multilocularis. We report the case of a patient who developed an accelerated course of AE with diffuse liver involvement after high-dose steroid treatment for autoimmune encephalitis. Immunosuppressive therapies present us with new challenges regarding the management of AE. With this article, we would like to draw attention to the importance of a screening program for AE before planned immunosuppressive therapy.

Late diagnosis and treatment may increase morbidity and mortality among persons with hepatitis C virus (HCV) infection. We included all participants of the Swiss Hepatitis C Cohort Study (SCCS). We used unadjusted and adjusted logistic and Cox regressions to determine the association between the geographic origin of the participants and the following outcomes: antiviral treatment status; sustained virologic response; cirrhosis at enrolment; incident cirrhosis; loss to follow-up (LTFU); and mortality. The analyses were adjusted for sex, baseline age, education, source of income, alcohol consumption, injection drug use (IDU), HCV genotype, HIV or HBV coinfection, duration of HCV infection, time since enrolment, cirrhosis, (type of) HCV treatment, and centre at enrolment. Among 5,356 persons, 1,752 (32.7%) were foreign-born. IDU was more common among Swiss- (64.1%) than foreign-born (36.6%) persons. Cirrhosis at enrolment was more frequent among foreign- than Swiss-born persons, reflecting the high frequency of cirrhosis among Italian-born persons who acquired HCV between 1950 and 1970 in Italian healthcare settings. Although antiviral treatment coverage was similar, the sustained viral response rate was increased and the mortality was lower among foreign-vs. Swiss-born persons, with the lowest mortality in persons from Asia/Oceania. LTFU was more frequent in persons from Germany, Eastern and Southern Europe, and the Americas. In conclusion, in Switzerland, a country with universal healthcare, geographic origin had no influence on hepatitis C treatment access, and the better treatment outcomes among foreign-born persons were likely explained by their lower prevalence of IDU and alcohol consumption than among Swiss-born persons.

About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

Obesity and steatosis have been associated with liver disease progression in patients with compensated advanced chronic liver disease (cACLD) (liver stiffness measurement [LSM] ≥ 10 kPa). The controlled attenuation parameter (CAP) estimates steatosis during LSM by transient elastography. We aimed to evaluate whether CAP is associated with the development of clinically relevant events in cACLD. Consecutive patients with cACLD and CAP measurements observed between September 2013 and September 2015 were retrospectively studied. Classical decompensation and severe bacterial infections on follow‐up were recorded. A predefined CAP cut‐off for steatosis was used (220 dB/m; 90% sensitivity). The association among LSM, CAP, and events was assessed by univariate and multivariate Cox regression. Among the 193 patients (viral etiology = 58%; median Child score = 5; LSM = 15.1 kPa; CAP = 255 ± 62 dB/m) who were followed up in median for 18 months, 18 developed clinically relevant events (11 liver decompensation, 7 severe bacterial infections). Patients developing events had higher LSM (median: 30.8 versus 14.3 kPa, P < 0.001) and showed trends for higher CAP (275 ± 46 versus 252 ± 63 dB/m, P = 0.07), lower platelet count (134 ± 74 versus 167 ± 74 G/L, P = 0.07), and worse liver function versus patients remaining compensated. Body mass index was similar in the two groups. All events were more frequent in patients with CAP being greater than or equal to 220 dB/m (12.9% versus 1.6% in CAP < 220; P = 0.013), and 10 of 11 episodes of liver decompensation occurred in patients with CAP being greater than or equal to 220 dB/m. Following multivariate analysis, LSM and CAP greater than or equal to 220 dB/m remained independently associated with clinical events in the whole population and in patients with clinically significant portal hypertension. Conclusion: The CAP being greater than or equal to 220 dB/m is associated with increased risk of clinical decompensation and bacterial infections independent of LSM in patients with cACLD and allows refining the noninvasive risk stratification in this population. (Hepatology Communications 2018; 00:000‐000) Obesity and steatosis have been associated with increased risk of progression and clinical events in patients with liver disease. We investigated whether Controlled attenuation parameter (CAP)‐ a new non‐invasive tool to quantify steatosis‐ could add to the prognostic stratification provided by liver stiffness measurement in patients with compensated advanced chronic liver disease (liver stiffness >10 kPa). We found that CAP≥220 dB/m is associated with increased risk of clinical decompensation and bacterial infections independent of LSM in patients with cACLD and allows refining the non‐invasive risk stratification in this population.

A sofosbuvir/ledipasvir combination is part of a first-line treatment of hepatitis C. However, in patients concurrently treated with amiodarone, cardiac side effects have been described, resulting in an official warning in 2015 by the American Food and Drug Administration and the European Medicines Agency when combining those substances. This deprived numerous hepatitis C patients with concurrent cardiovascular problems of receiving this highly effective treatment. Here we present a treatment alternative with an elbasvir/grazoprevir regimen, based on our successful treatment of a patient under concurrent amiodarone therapy. Our observations indicate that patients treated with amiodarone can finally benefit from effective antiviral therapy.

The validity of Doppler echocardiographic (DE) measurement of systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately the invasive pressures. 241 patients were prospectively studied to evaluate the diagnostic accuracy of mPAP for the diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164 patients mainly for preoperative evaluation of heart valve dysfunction. The correlation between DE and RHC was better when mPAP (r=0.93) and not sPAP (r=0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP than sPAP. The following ROC analysis identified that a mPAP≥25.5 mmHg is useful for the diagnosis of PH. This value was validated in an independent cohort of patients (n=50) with the suspicion of chronic-thromboembolic pulmonary hypertension. The calculated diagnostic accuracy was 98%, based on excellent sensitivity of 98% and specificity of 100%. The corresponding positive and negative predictive values were 100%, respectively 88%. mPAP has been found to be highly accurate for the initial diagnosis of PH. A cut-off value of 25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom RHC might be beneficial.