Seroprevalence of hepatitis E virus in patients with chronic liver disease.

INTRODUCTION: The seroprevalence of hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is little known in Brazil. Studies have suggested that HEV may harmfully influence the course of CLD, with a higher risk of progression to cirrhosis. OBJECTIVE: To estimate the prevalence of the anti-HEV antibody (IgG) in patients with CLD and to describe demographic data and risk factors, as well as clinical-laboratory and ultrasound parameters. PATIENTS AND METHODS: Cross-sectional study that included 227 patients with CLD followed at a referral outpatient clinic from June 2022 to March 2023. The patients were investigated clinically and tested for liver functions, anti-HEV IgG and, in positive cases, for HEV-RNA. Ultrasonography of the upper abdomen was also carried out. RESULTS: Investigation of 227 patients (50 with hepatitis B, 49 with nonalcoholic fatty liver disease, 33 with hepatitis C, 17 with alcoholic liver disease, 16 with schistosomiasis and 62 with mixed disease), 55.5% were female, with an average age of 57 ± 13 years; 37.9% had liver cirrhosis. Seven patients (3.08%) presented anti-HEV positive and HEV-RNA negative. Ultrasound identified association between anti-HEV and contact with pigs, presence of gynecomastia or palmar erythema, lower platelet count, higher APRI and FIB-4 values, and splenomegaly. CONCLUSION: Although the prevalence of anti-HEV in patients with CLD was low in this study, the antibody was observed more frequently in cases with a history of contact with pigs and with clinical-laboratory or imaging evidence of more advanced chronic liver disease.

Schistosomiasis of liver graft as a differential diagnosis of abnormal liver tests after transplantation: report of two cases.

Schistosomiasis is a major health problem that affects over 200 million people worldwide. There are few reports of Schistosoma mansoni found in liver transplants as well as scarce information about the course of the disease and the long-term effects on the graft. Herein, we report two cases of schistosomiasis in liver transplant recipients who presented abnormal serum liver enzymes, with evidence of gradual improvement after antiparasitic treatment. Furthermore, we discuss the possible role of screening the parasite infection in potential liver transplant recipients from endemic areas.

Schistosomiasis of liver graft as a differential diagnosis of abnormal liver tests after transplantation: report of two cases

ABSTRACT Schistosomiasis is a major health problem that affects over 200 million people worldwide. There are few reports of Schistosoma mansoni found in liver transplants as well as scarce information about the course of the disease and the long-term effects on the graft. Herein, we report two cases of schistosomiasis in liver transplant recipients who presented abnormal serum liver enzymes, with evidence of gradual improvement after antiparasitic treatment. Furthermore, we discuss the possible role of screening the parasite infection in potential liver transplant recipients from endemic areas.

Treatment of Hepatitis C with Direct-Acting Antivirals does not Induce Significant Arrhythmias

Abstract Background Chronic Hepatitis C (CHC) therapy with direct-acting antivirals (DAAs) has high efficacy and safety, but some cases of bradyarrhythmias have been described. Objective To evaluate heart rhythm disorders during DAA treatments. Methods Forty-eight patients with CHC (mean 61 years of age; 56% males; 73% HCV genotype 1) were evaluated before and during treatment with DAAs, analyzed by a resting 12-lead ECG [PR, QRS, and QT corrected (QTc) intervals measured] and a 24-h-Holter system, to evaluate the heart rate (HR) and the occurrence of arrhythmias. The Student's t-test or the Wilcoxon-Mann-Whitney test for continuous, independent variables were performed with a statistically significant p-value < 0.05. Results The electrocardiographic parameters before and during treatment were: PR interval (147.2 ± 15.6 vs 144.9 ± 15.6 ms; p = 0.21), QTc interval (427 ± 22.3 vs 421.7 ± 25.3 ms; p = 0.24), minimum HR (52.7 ± 8.4 vs 53.2 ± 8.5 bpm; p = 0.49), median HR (74.2 ± 10.4 vs 75.2 ± 9 bpm; p = 0.83), and maximum HR (117.4 ± 16.8 vs 117.9 ± 16.3 bpm; p = 0.25). These parameters proved to be similar among 11 beta-blockers or 22 ribavirin users. During treatment, the 21 cirrhotic patients presented significantly lower median HRs (72.1 ± 9.0 vs 77.9 ± 8.2 bpm; p = 0.02) and maximum HRs (108.9 ± 15.2 vs. 125.1 ± 13.2 bpm, p < 0.0001) through a 24-h-Holter monitoring than the patients without cirrhosis. No clinically relevant arrhythmias were detected. Conclusion DAAs do not significantly influence heart rate or induce significant cardiac arrhythmias in patients with CHC.

Visceral Leishmaniasis: A Case Report of a Challenging Diagnosis After Orthotopic Liver Transplantation.

Leishmaniasis is a disease caused by a protozoan and transmitted by sandfly species in several emerging countries. Visceral leishmaniasis is a serious complication, especially in immunosuppressed patients, and is uncommon after liver transplantation. We report the case of a 48-year-old female patient who underwent liver transplantation owing to polycystic liver disease. Six months after the procedure, she was hospitalized with diarrhea, acute kidney failure, and leukopenia. She had been off steroids for 3 months and was taking mycophenolate and tacrolimus. She had already been treated for cytomegalovirus, which was negative on admission. During hospitalization, fever, splenomegaly, ascites, and pancytopenia appeared. Serology for Leishmania by indirect immunofluorescence was negative. Then, bone biopsy and molecular testing for Leishmania diagnosed it as visceral leishmaniasis. Amphotericin therapy was initiated with resolution of fever after 4 days of treatment and gradual recovery from pancytopenia. This case highlights the challenge of early diagnosis of visceral leishmaniasis in liver transplant recipients with diarrhea and leukopenia, which can be caused by immunosuppression or more prevalent viral diseases. Late onset of fever, splenomegaly, and a first negative serologic test also made early diagnosis difficult. The aim of the report is to emphasize the suspicion of visceral leishmaniasis in symptomatic patients from emerging countries and to question the benefit of including protozoan screening in liver transplant donors and recipients in endemic areas.

Assessment of periportal fibrosis in Schistosomiasis mansoni patients by proton nuclear magnetic resonance-based metabonomics models.

BACKGROUND: The evaluation of periportal fibrosis (PPF) is essential for a prognostic assessment of patients with Schistosomiasis mansoni. The WHO Niamey Protocol defines patterns of fibrosis from abdominal ultrasonography, 1H-nuclear magnetic resonance (NMR)-based metabonomics has been employed to assess liver fibrosis in some diseases. AIM: To build 1H-NMR-based metabonomics models (MM) to discriminate mild from significant periportal PPF and identify differences in the metabolite profiles. METHODS: A prospective cross-sectional study was performed on schistosomiasis patients at a University Hospital in Northeastern Brazil. We evaluated 41 serum samples from 10 patients with mild PPF (C Niamey pattern) and 31 patients with significant PPF (D/E/F Niamey patterns). MM were built using partial least squares-discriminant analysis (PLS-DA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) formalisms. RESULTS: PLS-DA and OPLS-DA resulted in discrimination between mild and significant PPF groups with R2 and Q2 values of 0.80 and 0.38 and 0.72 and 0.42 for each model, respectively. The OPLS-DA model presented accuracy, sensitivity, and specificity values of 92.7%, 90.3%, and 100% to discriminate significant PPF. The metabolites identified as responsible by discrimination were: N-acetylglucosamines, alanine, glycolaldehyde, carbohydrates, and valine. CONCLUSION: MMs discriminated mild from significant PPF patterns in patients with Schistosomiasis mansoni through identification of differences in serum metabolites profiles.

Evaluation of Schistosomiasis Mansoni Morbidity by Hepatic and Splenic Elastography.

In patients with Mansoni schistosomiasis, it is fundamental to evaluate the disease morbidity, which is reflected by the severity of periportal fibrosis (PPF) and parameters of portal hypertension, as analyzed by ultrasonography (US). This study aimed to evaluate the morbidity of schistosomiasis by hepatic and splenic point shear-wave elastography (pSWE) and relate this to US parameters. The PPF pattern, the diameter of the portal and splenic veins and the size of the spleen were evaluated by US. Then, liver and spleen pSWEs were assessed in 74 patients using the same equipment. As the PPF pattern progressed, the splenic pSWE values significantly increased. Significant correlations between splenic pSWE, the longitudinal and transverse lengths of the spleen and the diameters of the portal and splenic veins were observed. These findings, however, were not observed through hepatic pSWE. In conclusion, the splenic pSWE has the potential for assessing morbidity in schistosomiasis mansoni.

A real-life study on the impact of direct-acting antivirals in the treatment of chronic hepatitis C in liver transplant recipients at two university centers in Northeastern Brazil.

The efficacy of direct-acting antivirals (DAAs) in the treatment of chronic hepatitis C (CHC) in liver transplant recipients is poorly understood, and several factors, including immunosuppression, drug interactions, elevated viraemia, and intolerance to ribavirin (RBV), can reduce cure rates. We conducted a real-life study on liver transplant recipients with CHC treated with a combination of sofosbuvir (SOF) and daclatasvir (DCV) or simeprevir (SIM), with or without RBV, followed-up for 12 to 24 weeks. The treatment effectiveness was assessed by determining the sustained virological response (SVR) rates at 12 or 24 weeks after the treatment cessation. Eighty-four patients were evaluated, with a mean age of 63.4 ± 7.4 years, HCV genotype 1 being the most prevalent (63.1%). Nineteen patients (22.7%) had mild fibrosis (METAVIR < F2) and 41 (48.8%) significant fibrosis (METAVIR ≥ F2). The average time between liver transplantation and the start of treatment was 4 years (2.1-6.6 years). The SOF + DCV regimen was used in 58 patients (69%). RBV in combination with DAAs was used in seven patients (8.3%). SVR was achieved in 82 patients (97.6%), and few relevant adverse events could be attributed to DAA therapy, including a patient who stopped treatment due to a headache. There was a significant reduction in ALT, AST, GGT and FA levels, or the APRI index after 4 weeks of treatment, which remained until 12/24 weeks post-treatment. DAA treatment of CHC in liver-transplanted patients achieved a high SVR rate and resulted in the normalization of serum levels of liver enzymes.

Anti-rod and ring antibodies in patients with chronic hepatitis C using direct-acting antivirals.

Anti-rods and rings (anti-RR) antibody induction is related to the combination of interferon and ribavirin in the treatment of hepatitis C virus (HCV) infection. If the main factor leading to this autoimmune reaction is the combination of these drugs, is not well known, but in vitro studies shows that ribavirin alone can induce rods and rings structures. New direct-acting antivirals (DAAs) permit HCV treatment without needing interferon but may be associated with ribavirin in the most difficult-to-treat patients. The aim of this study is to evaluate the occurrence of anti-RR in patients with chronic HCV infection, before and after 12 weeks of treatment with DAAs, with and without ribavirin. From Jun 2016 to Oct 2017, 52 HCV-infected patients were screened for anti-RR before and after DAA therapy, including sofosbuvir, daclatasvir, simeprevir, and ribavirin. Serum samples were analyzed using indirect immunofluorescence. The anti-RR was present in 11 (21%) of the 52 patients (51.9% male and mean age of 59.1 years) before using DAAs. All of them had been previously treated and previous exposed to interferon/ribavirin, with exposure time to ribavirin associated with the presence of anti-RR. After 12 weeks of DAA treatment, 3 patients (5.7%) developed the antibody in low titers, and two of them (66%) were interferon/ribavirin experienced. Only one of the 29 naïve patients (3.44%) developed anti-RR during the current treatment. Anti-RR was present in patients previously treated with interferon/ribavirin and can emerge after DAA treatment probably at a lower frequency than after interferon/ribavirin treatment.

Long-term persistence of anti-rods and rings antibodies in patients with chronic hepatitis C after antiviral treatment.

Anti-rods and rings (anti-RR) antibodies are related to hepatitis C virus (HCV) in patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Only RBV induces rods/rings structures in vitro; but in vivo, the antibody appearance is related to the combination of these drugs, because data about patients using just one of these drugs alone is missing. Some studies suggest disappearance of these antibodies over time. The aim of this study was to describe the occurrence of anti-RR in patients with chronic hepatitis C treatment-naïve or previously PEG-IFN/RBV-experienced, evaluating the persistence of anti-RR antibodies long after PEG-IFN/RBV treatment. From 2016 to 2017, 70 HCV-infected patients were screened for anti-RR using indirect immunofluorescence. Demographic and clinical data about previous treatments against HCV were assessed. Thirty-four patients (49%) had been previously treated with PEG-IFN/RBV and the average time since they had received the last antiviral treatment was 85.4 months. Anti-RR seropositivity was detected in 16 patients (23%), and all of these had used PEG-IFN/RBV (corresponding to 47% of experienced patients). Previous antiviral treatment and previous exposure time to RBV were associated with anti-RR positivity. Median time elapsed since last treatment was similar between anti-RR-positive and anti-RR-negative patients. Anti-RR seropositivity was not observed in treatment-naïve patients, but was detected in almost half of patients previously treated with PEG-IFN and RBV, even after a long period without exposure to these drugs. This antibody was related to extended prior exposure to ribavirin.

Proton nuclear magnetic resonance-based metabonomic models for non-invasive diagnosis of liver fibrosis in chronic hepatitis C: Optimizing the classification of intermediate fibrosis.

AIM: To develop metabonomic models (MMs), using 1H nuclear magnetic resonance (NMR) spectra of serum, to predict significant liver fibrosis (SF: Metavir ≥ F2), advanced liver fibrosis (AF: METAVIR ≥ F3) and cirrhosis (C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C (CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4). METHODS: Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS: Results showed that forty-two patients (61%) presented SF, 28 (40%) AF and 18 (26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27 (39.7%) and 25 (38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION: The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.

Diagnosis of coinfection by schistosomiasis and viral hepatitis B or C using 1H NMR-based metabonomics.

BACKGROUND: Diagnosis of liver involvement due to schistosomiasis in asymptomatic patients from endemic areas previously diagnosed with chronic hepatitis B (HBV) or C (HCV) and periportal fibrosis is challenging. H-1 Nuclear Magnetic Resonance (NMR)-based metabonomics strategy is a powerful tool for providing a profile of endogenous metabolites of low molecular weight in biofluids in a non-invasive way. The aim of this study was to diagnose periportal fibrosis due to schistosomiasis mansoni in patients with chronic HBV or HCV infection through NMR-based metabonomics models. METHODOLOGY/PRINCIPAL FINDINGS: The study included 40 patients divided into two groups: (i) 18 coinfected patients with schistosomiasis mansoni and HBV or HCV; and (ii) 22 HBV or HCV monoinfected patients. The serum samples were analyzed through H-1 NMR spectroscopy and the models were based on Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA). Ultrasonography examination was used to ascertain the diagnosis of periportal fibrosis. Exploratory analysis showed a clear separation between coinfected and monoinfected samples. The supervised model built from PLS-DA showed accuracy, R2 and Q2 values equal to 100%, 98.1% and 97.5%, respectively. According to the variable importance in the projection plot, lactate serum levels were higher in the coinfected group, while the signals attributed to HDL serum cholesterol were more intense in the monoinfected group. CONCLUSIONS/SIGNIFICANCE: The metabonomics models constructed in this study are promising as an alternative tool for diagnosis of periportal fibrosis by schistosomiasis in patients with chronic HBV or HCV infection from endemic areas for Schistosoma mansoni.