Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

Purpose: Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. Methods: The sera of 51 treatment-naïve AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. Results: According to the results of enzyme-linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and >99.9% for the diagnosis of CE and AE, respectively. Antigens derived from E. multilocularis metacestodes had sensitivities ranging from 84 to 91% and >99.9% for the diagnosis of CE and AE, respectively. Specificities ranged from 92 to >99.9%. Post-test probabilities for the differential diagnosis of AE from liver neoplasias, CE from cystic liver lesions, and screening for AE in Switzerland were around 95, 86 and 2.2%, respectively. Cross-reactions with antibodies in sera of patients with other parasitic affections (fasciolosis, schistosomosis, amebosis, cysticercosis, and filarioses) did occur at variable frequencies, but could be eliminated through the use of confirmatory testing. Conclusions: Different metacestode-derived antigens of E. granulosus and E. multilocularis are valuable, widely accessible, and cost-efficient tools for the serological diagnosis of echinococcosis. However, confirmatory testing is necessary, due to the lack of species specificity and the occurrence of cross-reactions to other helminthic disease

Hepatitis C virus dynamics among intravenous drug users suggest that an annual treatment uptake above 10% would eliminate the disease by 2030.

In Switzerland, the prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) has been decreasing owing to active harm reduction efforts and an aging population. Recent advances in HCV therapeutics may provide an opportunity to direct treatment to high-risk populations, with a goal of reducing HCV prevalence and preventing new infections. In order to guide these efforts, the current project was undertaken with the following aims: (1) to develop a simple model to estimate the number of new HCV infections using available data on PWID; (2) to examine the impact of intervention strategies (prevention and treatment) on new and total HCV infections among PWID. A dynamic HCV transmission model was used to track HCV incidence and prevalence among active PWID according to their harm reduction status. The relative impact of treating 1, 5, 10 or 15% of HCV+ PWID with new oral direct acting antivirals was considered. In 2015, there were an estimated 10 160 active PWID in Switzerland, more than 85% of whom were engaged in harm reduction programmes. Approximately 42% of active PWID were HCV-RNA+, with 55 new viraemic infections occurring annually. By 2030, a 60% reduction in the HCV+ PWID population would be expected. In the absence of behavioural changes, the number of secondary infections would increase under all treatment scenarios. With high level treatment, the number of secondary infections would peak and then drop, corresponding to depletion of the viral pool. In Switzerland, 5% treatment of the 2015 HCV+ PWID population per year would result in a 95% reduction in total cases by 2030, whereas ≥10% treatment would result in a >99% reduction. Timely treatment of hepatitis C virus among people who inject drugs is necessary to reduce the prevalence and prevent new infections in Switzerland

The current and future burden of hepatitis B in Switzerland: a modelling study.

Chronic hepatitis B infection (defined as sustained detection of hepatitis B virus [HBV] surface antigen [HBsAg] protein in serum) is a leading cause of cirrhosis, hepatocellular carcinoma and liver-related deaths. A situation analysis carried out by the Swiss Federal Office of Public Health estimated the HBsAg prevalence in Switzerland to be 0.53% (95% CI: 0.32-0.89%) in 2015 (~44,000 cases). A lower prevalence of chronic HBV in the younger generation and the adoption of universal coverage in the first year of life are expected to decrease the burden of HBV; however, a number of people in key populations (including migrants) remain undiagnosed and untreated, and infected individuals remain at risk of progressing to cirrhosis, hepatocellular carcinoma and death. Our primary objective was to examine the current and estimate the future disease burden of HBV in Switzerland and the impact of migration. The secondary objective was to estimate the impact of changing future treatment numbers. A modelling study was performed using an existing, validated model (PRoGReSs Model) applied to the Swiss context. Model inputs were selected through a literature search and expert consensus. Population data from the Federal Statistical Office were used alongside prevalence data from the Polaris Observatory to estimate the number of HBV infections among people born abroad. The PRoGReSs Model was populated with and calibrated to the available data and what-if scenarios were developed to explore the impact of intervention on the future burden of disease. A Monte Carlo simulation was used to estimate 95% uncertainty intervals (95% UIs). In 2020, there were an estimated 50,100 (95% UI: 47,500-55,000) HBsAg+ cases among people born abroad. Among people born in Switzerland, there were approximately 62,700 (UI: 58,900-68,400) total HBV infections (0.72% [UI: 0.68-0.79%] prevalence). Prevalence among infants and children under the age of 5 were both <0.1%. By 2030, prevalence of HBV is expected to decrease, although morbidity and mortality will increase. Increasing diagnosis (90%) and treatment (80% of those eligible) to meet the global health sector strategy on viral hepatitis programme targets could prevent 120 cases of hepatocellular carcinoma and 120 liver-related deaths. Thanks to the historical vaccination programmes and the continued rollout of universal 3-dose coverage in the first year of life, Switzerland is expected to exceed the global health sector strategy targets for the reduction of incidence. While overall prevalence is decreasing, the current diagnosis and treatment levels remain below global health sector strategy targets

Multiple infarcted regenerative nodules in liver cirrhosis after decompensation of cirrhosis: a case series

These patients showed focal liver lesions, to be considered in the differential diagnosis of cirrhotic livers. Infarcted regenerative nodules may be underdiagnosed in patients with decompensation of cirrhosis. In order to differentiate these lesions from malignant tumors, serial imaging seems to be helpful. However, the main differential diagnosis should be an abscess. It is important to know the wide spectrum of image appearances of these lesions. Hypotension can lead to a reduction of portal and arterial liver flow. Since variceal bleeding or septic shock can induce hypotension - as observed in our patients - we conclude that this leads to infarction of such nodules

Histopathological evidence of invasive gastric mucormycosis after transarterial chemoembolization and liver transplantation

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8months earlier and 40days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5weeks, followed by 7weeks of posaconazole. Follow-up biopsies after 1 and 5months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication

Histopathological evidence of invasive gastric mucormycosis after transarterial chemoembolization and liver transplantation

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8months earlier and 40days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5weeks, followed by 7weeks of posaconazole. Follow-up biopsies after 1 and 5months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication

Pathology of Echinococcosis

Infection of humans by the larval stage of the tapeworms Echinococcus granulosus sensu lato or Echinococcus multilocularis causes the life-threatening zoonoses cystic echinococcosis (CE) and alveolar echinococcosis (AE). Although cystic liver lesions are a hallmark of both diseases, course, prognosis, and patients' management decisively differ between the two. The wide and overlapping spectrum of morphologies and the limited availability of ancillary tools are challenges for pathologists to reliably diagnose and subtype echinococcosis. Here, we systematically and quantitatively recorded the pathologic spectrum in a clinically and molecularly defined echinococcosis cohort (138 specimens from 112 patients). Immunohistochemistry using a novel monoclonal antibody (mAbEmG3) was implemented, including its combined application with the mAbEm2G11. Six morphologic criteria sufficiently discriminated between CE and AE: size of smallest (CE/AE: >2/≤2 mm) and largest cyst (CE/AE: >25/≤25 mm), thickness of laminated layer (CE/AE: >0.15/≤0.15 mm) and pericystic fibrosis (CE/AE: >0.6/≤0.6 mm), striation of laminated layer (CE/AE: moderate-strong/weak), and number of cysts (CE/AE: ≤9/>9). Combined immunohistochemistry with mAbEm2G11 (E. multilocularis specific) and mAbEmG3 (reactive in AE and CE) was equally specific as and occasionally more sensitive than polymerase chain reaction. On the basis of these findings, we developed a diagnostic algorithm for the differential diagnosis of echinococcosis. In summary, we have not only identified the means to diagnose echinococcosis with greater certainty, but also defined morphologic criteria, which robustly discriminate between CE and AE. We expect our findings to improve echinococcosis diagnostics, especially of challenging cases, beneficially impacting the management of echinococcosis patients

Autochthonous hepatitis E as a cause of acute-on-chronic liver failure and death: histopathology can be misleading but transaminases may provide a clue.

Acute decompensation and death have been observed in patients with acute hepatitis E virus (HEV) infection and preexisting liver cirrhosis. However, the clinical, laboratory and histological features need to be fully characterised. Some of us recently described the histological presentation of hepatitis E in a large panel of liver tissue specimens. Here, we conducted a case-control study to investigate the clinical and laboratory features of the subset of patients with HEV-related acute-on-chronic liver failure (ACLF) and death. Each patient was matched to three control patients with histologically confirmed severe alcoholic hepatitis based on sex, age, total bilirubin, INR, serum creatinine and MELD score on admission. Of 5 patients who died in a context of HEV-related ACLF, 3 (60%) were male and the median age was 66 years (range 51–76). Median alanine aminotransferase (ALT) at presentation was 2610 U/l (range 705–3134) and aspartate aminotransferase (AST) 2818 U/l (range 1176–8611). Liver function was heavily altered in all patients. Histological analyses revealed steatohepatitis on a background of cirrhosis, suggestive of an alcoholic or nonalcoholic origin. Based on histopathology, alcoholic hepatitis was initially suspected in two patients and corticosteroid treatment was initiated. Ribavirin was started in four patients. Median time from hospitalisation to death was 17 days (range 6–25 days). AST levels in patients with HEV-related ACLF were significantly higher as compared to the matched patients with severe alcoholic hepatitis. Typical histopathological features of viral hepatitis may be absent in ACLF caused by HEV infection. HEV infection should be sought in acute decompensation of cirrhosis and ACLF even in the absence of histological changes suggesting viral infection