Percutaneous drainage and combined praziquantel-albendazole therapy: a novel approach for the treatment of simple echinococcal liver cysts.

Cystic echinococcosis (CE) is a worldwide helminthic zoonosis causing serious disease in humans. The WHO Informal Working Group on Echinococcosis recommends a stage-specific treatment approach of hepatic CE that facilitates the decision on what therapy option is most appropriate. Percutaneous aspiration, instillation of a scolicide, e.g., ethanol or hypertonic saline, and subsequent re-aspiration (PAIR) have been advocated for treating medium-size unilocular WHO-stage CE1 cysts. PAIR can pose a risk of toxic cholangitis because of spillage of ethanol in the case of a cysto-biliary fistula or of life-threatening hypernatriaemia when hypertonic saline is used. The purpose of our study is to develop an alternative, safe, minimally invasive method to treat CE1 cysts, avoiding the use of toxic topic scolicides.We opt for percutaneous drainage (PD) in four patients: the intrahepatic drainage catheter is placed under CT-fluoroscopy, intracystic fluid is aspirated, and the viability of intracystic echinococcal protoscolices is assessed microscopically. Oral praziquantel (PZQ) is added to albendazole (ABZ) instead of using topical scolicidals.Protoscolices degenerate within 5 to 10 days after PZQ co-medication at a cumulative dosage of 250 to 335 mg/kg, and the cysts collapse. The cysts degenerate, and no sign of spillage nor relapse is observed in the follow-up time of up to 24 months post-intervention.In conclusion, PD combined with oral PZQ under ABZ coverage is preferable to PAIR in patients with unilocular echinococcal cysts.

Treating hepatitis D with bulevirtide - Real-world experience from 114 patients.

Background & Aims: Bulevirtide is a first-in-class entry inhibitor of hepatitis B surface antigen. In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepatocellular carcinoma. Herein, we report the first data from a large multicenter real-world cohort of patients with hepatitis D treated with bulevirtide at a daily dose of 2 mg without additional interferon. Methods: In a joint effort with 16 hepatological centers, we collected anonymized retrospective data from patients treated with bulevirtide for chronic hepatitis D. Results: Our analysis is based on data from 114 patients, including 59 (52%) with cirrhosis, receiving a total of 4,289 weeks of bulevirtide treatment. A virologic response defined as an HDV RNA decline of at least 2 log or undetectable HDV RNA was observed in 87/114 (76%) cases with a mean time to virologic response of 23 weeks. In 11 cases, a virologic breakthrough (>1 log-increase in HDV RNA after virologic response) was observed. After 24 weeks of treatment, 19/33 patients (58%) had a virologic response, while three patients (9%) did not achieve a 1 log HDV RNA decline. No patient lost hepatitis B surface antigen. Alanine aminotransferase levels improved even in patients not achieving a virologic response, including five patients who had decompensated cirrhosis at the start of treatment. Treatment was well tolerated and there were no reports of drug-related serious adverse events. Conclusions: In conclusion, we confirm the safety and efficacy of bulevirtide monotherapy in a large real-world cohort of patients with hepatitis D treated in Germany. Future studies need to explore the long-term benefits and optimal duration of bulevirtide treatment. Impact and implications: Clinical trials proved the efficacy of bulevirtide for chronic hepatitis D and led to conditional approval by the European Medical Agency. Now it is of great interest to investigate the effects of bulevirtide treatment in a real-world setting. In this work, we included data from 114 patients with chronic hepatitis D who were treated with bulevirtide at 16 German centers. A virologic response was seen in 87/114 cases. After 24 weeks of treatment, only a small proportion of patients did not respond to treatment. At the same time, signs of liver inflammation improved. This observation was independent from changes in hepatitis D viral load. The treatment was generally well tolerated. In the future, it will be of interest to investigate the long-term effects of this new treatment.

Real-life experiences with bulevirtide for the treatment of hepatitis delta-48 weeks data from a German centre.

In July 2020, the entry inhibitor bulevirtide was approved in the European Union for the treatment of chronic hepatitis delta virus (HDV) infection. We describe the first 48 weeks of bulevirtide therapy in eight patients (n = 7 male, n = 1 female; n = 3 compensated cirrhosis) treated at our centre. Median ALT values declined from 82 to 34 U/L after 48 weeks. Median HDV RNA dropped from 13 380 000 to 3135 copies/ml. One patient showed no significant response and was discontinued at week 16. Overall, we observed a favourable safety profile and a marked biochemical and virological response in the majority of our patients.

Performance characterization of a novel electronic number connection test to detect minimal hepatic encephalopathy in cirrhotic patients.

BACKGROUND AND AIM: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, characterized by cognitive deficits that negatively impact patients' quality of life. The mild, minimal hepatic encephalopathy (mHE) can only be detected by psychometric tests and early mHE detection can prevent more severe complications or even survival times. Here, we aimed to investigate the feasibility and validity of the novel-developed electronic number connection test (eNCT), which is designed as a fast and easy-to-perform mHE patient self-test. METHODS: The eNCT design was inspired by the paper-pencil number connection test version A, showing 25 numbers on the screen (1-25), in a random order. The time required to tap on all digits in the correct order was measured. A total of 238 individuals (112 patients with liver cirrhosis) were enrolled in this study and eNCT times were compared with well-established paper-pencil tests. The Psychometric Hepatic Encephalopathy Score test battery was used to detect mHE and cut-off values for mHE detection by the eNCT were defined. RESULTS: Overall, cirrhotic patients showed significantly slower test completion times compared with control participants. The eNCT performance was inversely correlated with Psychometric Hepatic Encephalopathy Score test performance in cirrhotic patients, independent of the HE status. Thirty cirrhotic patients fulfilled the mHE criteria and receiver operating characteristic curve analysis showed high sensitivity (>82%) and specificity (>85%) for mHE detection. Finally, the eNCT showed excellent test-retest reliability (intraclass correlation coefficient=0.94). CONCLUSION: The novel eNCT is a reliable HE self-test to monitor cognitive function and detect cognitive impairment in cirrhotic patients.

Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study.

BACKGROUND: Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa is highly effective, but can be associated with frequent side-effects. We investigated the safety and efficacy of an interferon-free regimen for treatment of acute HCV infection. METHODS: In this prospective, open-label, multicentre, single-arm pilot study, we enrolled adults (≥18 years) with acute HCV genotype 1 monoinfection from ten centres in Germany. Patients were given ledipasvir (90 mg) plus sofosbuvir (400 mg) as a fixed-dose combination tablet once daily for 6 weeks. The primary efficacy outcome was the proportion of patients with sustained virological response (defined as undetectable HCV RNA 12 weeks after the end of treatment; other primary outcomes were safety and tolerability of ledipasvir plus sofosbuvir. The primary analysis population consisted of all patients who received at least one dose of study drug. Safety was also assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, number NCT02309918. FINDINGS: Between Nov 19, 2014, and Nov 10, 2015, we enrolled 20 patients. Median HCV RNA viral load at baseline was 4·04 log10 IU/mL (1·71-7·20); 11 patients were infected with HCV genotype 1a and nine patients with genotype 1b. All patients achieved a sustained virological response 12 weeks after the end of treatment (20 [100%] of 20 patients). Treatment was well tolerated; there were no drug-related serious adverse events. Up to 12 weeks after treatment, 22 possible or probable drug-related adverse events were reported. There was one serious adverse event, which was judged unrelated to the study drug; one patient was admitted to hospital for surgery of a ruptured cruciate ligament. INTERPRETATION: Treatment for 6 weeks with ledipasvir plus sofosbuvir was well tolerated and highly effective in patients with acute HCV genotype 1 monoinfection. Short-duration treatment of acute hepatitis C might prevent the spread of HCV in high-risk populations. FUNDING: Gilead Sciences, HepNet Study-House/German Liver Foundation, and German Centre for Infection Research (DZIF).

High prevalence of anti-hepatitis E virus antibodies in outpatients with chronic liver disease in a university medical center in Germany.

AIM/OBJECTIVES/BACKGROUND: Hepatitis E virus (HEV) is an emerging disease in developed countries. HEV seroprevalence ranges from 3.2 to 10% in Europe, but is higher in endemic areas such as southern France. In Germany, an increasing incidence of HEV infections has been reported recently. Risk factors for the acquisition of HEV are incompletely understood. METHODS: We screened 295 consecutive patients with chronic liver disease attending the outpatient department at Charité University Hospital for HEV seroprevalence. Epidemiological characteristics were analyzed and patients were questioned for risk factors using a standardized questionnaire. A total of 78 patients without known liver disease were also tested for HEV IgG. RESULTS: Out of 295 screened patients, 62 tested positive for HEV-IgG. Overall, 50% of the HEV-positive patients were women and 23.8% had underlying liver cirrhosis. HEV-positive patients were older than HEV-negative patients (mean age 56 vs. 48.6 years). Seroprevalence increased with age from 13% in patients 30-39 years of age to 36.4% in patients 70-79 years of age. Of the total, 46.7% of HEV-IgG-positive patients had contact with domestic animals and 38.3% had received blood transfusions. A total of 50% of the HEV-IgG-positive patients had regularly consumed uncooked meat and 45% had regularly consumed wild game or wild boar, which was significantly more frequent than in HEV-IgG-negative patients. CONCLUSION: HEV-IgG seroprevalence was 21% in a cohort of patients with chronic liver disease and 24.4% in a cohort of patients without known liver disease. The higher seroprevalence found among elderly patients suggests a lifetime accumulation of risk of exposure to HEV. The results from this study imply that regular testing should be performed for HEV in developed countries in case of liver disease of unknown etiology.

Insecticide-treated mosquito nets in rural Burkina Faso: assessment of coverage and equity in the wake of a universal distribution campaign.

Insecticide-treated mosquito nets (ITNs) are an essential tool of the Roll Back Malaria strategy. An increasing number of African countries have embarked on mass distribution campaigns of long-lasting insecticide-treated nets (LLINs) with the ultimate goal of universal coverage. Such a national campaign with the goal of one ITN for every two people has been conducted in Burkina Faso in 2010. Our aim was to assess the coverage and equity effect of the universal distribution campaign of LLINs in Burkina Faso and to identify determinants of ITN ownership across households after the campaign. We evaluated its effects through comparison of data from two household surveys conducted in early 2010 (before the campaign) and early 2011 (after the campaign) on a representative rural district in north-western Burkina Faso. Data were collected on household characteristics (including socio-economic status) and ITN ownership. We used concentration curves and indices to compare ITN coverage indicators before and after the campaign and multilevel multivariate logistic regression to estimate factors associated with achievement of the universal coverage target in 2011. The survey included 1106 households in 2010 and 1094 in 2011. We found that the proportion of households with at least one ITN increased from 59% before the campaign to 99% afterwards, whereas the concentration index dropped from 0.087 (standard error (SE): 0.014) to 0.002 (SE: 0.002). Fifty-two per cent of households reached the target of one ITN for every two people per household, with the relevant concentration index at -0.031 (SE: 0.016). Eighty-six per cent of households owned at least one ITN for every three people. The main characteristics significantly associated with the targeted intra-household coverage were family size and distance to the health centre but not socio-economic status. In conclusion, despite not having fully met its target, the national LLIN campaign achieved a high level of coverage and fostered equity.