EASL position paper on clinical follow-up after HCV cure.

Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.

Peer support for people living with hepatitis B virus-A foundation for treatment expansion.

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals.

Is It Possible to Eliminate Postoperative Shunt Infections?: Results of a Modified Hydrocephalus Clinical Research Network Protocol.

BACKGROUND: Postoperative shunt infection is a nightmare in neurosurgical practice with additional morbidity and mortality. A lot of protocols have contributed to the reduction of ventriculoperitoneal shunt (VPS) infections but not eradication. The aim of the study was to evaluate the rigid application of a modified Hydrocephalus Clinical Research Network (HCRN) protocol in the prevention of postoperative shunt infection. METHODS: We retrospectively evaluated children with congenital hydrocephalus who underwent VPS insertion, and in whom the protocol was applied from June 2019 to January 2020. Follow-up ranged from 11 to 24 months. RESULTS: Thirty-seven procedures were performed including 35 primary shunt insertions and two revision surgeries. The median age was 5 months (range, 1-30 months), and 25 patients were males. The most common cause for VPS placement was congenital hydrocephalus without identifiable cause in 28 cases (80%). The endoscope-assisted technique was used in the insertion of the proximal end in six cases (17%). The mean follow-up was 19.4 months (11-24 months). The rate of shunt infection was 0% till the last follow-up. CONCLUSION: The preliminary results showed an effective method for the prevention of postoperative shunt infections using the modified protocol. These initial findings need to be validated in a large prospective study before widespread application can be recommended.

Bilaterality of varicocele: The overlooked culprit in male infertility. Case series study.

OBJECTIVES: Varicocele is the most common correctable cause of male infertility that always has been a debatable subject as regards how it affects fertility and the best way to treat it. Proper assessment of the disease bilaterality is crucial not to miss one side and not to jeopardize treatment outcome. This study aimed to objectively assess varicocele bilaterality in infertile men aiming to improve treatment outcome in this cohort of patients. METHODS: This prospective study was conducted between January 2019 and January 2022 including infertile males with varicoceles. Assessment of missed concomitant contralateral varicocele done pre-operatively by Color Doppler Ultrasound and intraoperatively by intraoperative Doppler device and measurement of maximal vein diameter of contralateral side. RESULTS: A total of 329 cases completed the study. A hundred cases (30.4%) were initially referred as unilateral varicoceles and 229 (69.6%) as bilateral varicoceles. After reassessment of the study population, bilaterality of varicocele was found to be as high as 98.5% (324/329). Repeat CDUS strongly correlated with the intraoperative measured varicocele diameter (r = 0.9, p < 0.001). Moreover, sperm parameters showed significant improvement 3 and 6 months post varicocelectomy. Normal pregnancy after 1 year of surgery occurred in 118 cases (35.9%). CONCLUSIONS: Varicocele bilaterality in infertile men is underreported. Thorough assessment by expert radiologists and andrologists is of paramount importance not to miss significant pathology or hazard treatment outcome.

Acute Kidney Injury and Diffuse Pulmonary Hemorrhage Secondary to IgA Nephropathy and Henoch-Schönlein Purpura: A Case Report.

IgA nephropathy (IgAN), characterized as immune complex-mediated glomerulonephritis, can occasionally manifest alongside the pulmonary-renal syndrome. Henoch-Schönlein purpura (HSP), an inflammatory condition affecting small vessels through leukocytoclastic vasculitis, exhibits a close association with IgA nephropathy. Nonetheless, HSP's infrequent complications encompass pulmonary hemorrhage. Notably, the onset of pulmonary hemorrhage can rapidly precipitate a grave decline in the patient's health status, carrying a potentially fatal outcome for both disorders. Moreover, the existing literature regarding this specific complication and its management, particularly among adults, remains relatively limited. We report a rare case of a 43-year-old male with acute renal failure secondary to IgA nephropathy associated with HSP, whose condition was further complicated by pulmonary hemorrhage. He was treated with extensive plasmapheresis, pulse steroids, rituximab, and cyclophosphamide, which led to the successful recovery of his kidney function. Recognizing the potential of various presentations can significantly contribute to early diagnosis and prompt treatment, potentially leading to an improved prognosis for these patients.

SELF-EXPANDING FOAM VS PRE-PERITONEAL PACKING FOR EXSANGUINATING PELVIC HEMORRHAGE.

BACKGROUND: Mortality for pelvic fracture patients presenting with hemorrhagic shock ranges from 21-57%. The objective of this study was to develop a lethal and clinically-relevant pelvic hemorrhage animal model with and without bony fracture for evaluating therapeutic interventions. ResQFoam is a self-expanding foam that has previously been described to significantly decrease mortality in large-animal models of abdominal exsanguination. We hypothesized that administration of ResQFoam into the pre-peritoneal space could decrease mortality in exsanguinating pelvic hemorrhage. METHODS: Two pelvic hemorrhage models were developed using non-coagulopathic swine. Pelvic hemorrhage model #1: bilateral, closed-cavity, major vascular retro-peritoneal hemorrhage without bony pelvic fracture. After injury, animals received no treatment (control, n = 10), underwent pre-peritoneal packing using laparotomy pads (n = 11), or received ResQFoam (n = 10) injected into the pre-peritoneal space. Pelvic hemorrhage model #2: unilateral, closed-cavity, retro-peritoneal hemorrhage injury (with intra-peritoneal communication) combined with complex pelvic fracture. After injury, animals received resuscitation (control, n = 12), resuscitation with pre-peritoneal packing (n = 10) or with ResQFoam injection (n = 10) into the pre-peritoneal space. RESULTS: For model #1, only ResQFoam provided a significant survival benefit. The median survival times were 50 and 67 minutes for pre-peritoneal packing and ResQFoam, compared to 6 minutes with controls (p = 0.002 and 0.057, respectively). Foam treatment facilitated hemodynamic stabilization and resulted in significantly less hemorrhage (21.5 ± 5.3 g/kg) relative to controls (31.6 ± 5.0 g/kg, p < 0.001) and pre-peritoneal packing (32.7 ± 5.4 g/kg, p < 0.001). For model #2, both ResQFoam and pre-peritoneal packing resulted in significant survival benefit compared to controls. The median survival times were 119 and 124 minutes for the pre-peritoneal packing and ResQFoam groups, compared to 4 minutes with controls (p = 0.004 and 0.013, respectively). CONCLUSIONS: Percutaneous injection of ResQFoam into the pre-peritoneal space improved survival relative to controls, and similar survival benefit was achieved compared to standard pre-peritoneal pelvic packing. The technology has potential to augment the armamentarium of tools to treat pelvic hemorrhage.Study Type: This is a Basic Science paper and, therefore, does not require level of evidence.

The Diagnostic and Therapeutic Dilemma of Seronegative Pulmonary Renal Syndrome: A Case Report.

Pulmonary renal syndrome (PRS) is a combination of rapid progressive glomerulonephritis (RPGN) and diffuse alveolar hemorrhage (DAH) caused by a variety of immunological and non-immunological etiologies. The difficulty in identifying and reporting seronegative PRS cases could be attributed to the lack of specific immunological markers. Thus, we report a rare case of a 13-year-old boy who was initially diagnosed with idiopathic pauci-immune pulmonary capillaritis (IPIPC). A year later, his condition became complicated, and was referred for further workup. During his hospital stay, he underwent a renal biopsy that showed stage II membranous nephropathy (MN). He tested negative for immunological markers and a diagnosis of seronegative PRS was established. He responded well to the immunosuppression therapy with monthly follow-ups. As in our patient, PRS may manifest as acute renal failure symptoms and non-specific respiratory symptoms that require extensive workup. The severity of the disease is inferred from the renal function at the time of presentation. Management involves immunosuppression and treatment of the underlying condition, with dialysis dependency occurring in a significant percentage of patients and a high mortality rate, especially in critically ill and older patients. In conclusion, timely diagnosis and treatment are essential given the condition's rapid progression and high mortality rate.

Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach.

Nonalcoholic steatohepatitis (NASH) might soon become the leading cause of end-stage liver disease and indication for liver transplantation worldwide. Fibrosis severity is the only histological predictor of liver-related morbidity and mortality in NASH identified to date. Moreover, fibrosis regression is associated with improved clinical outcomes. However, despite numerous clinical trials of plausible drug candidates, an approved antifibrotic therapy remains elusive. Increased understanding of NASH susceptibility and pathogenesis, emerging human multiomics profiling, integration of electronic health record data and modern pharmacology techniques hold enormous promise in delivering a paradigm shift in antifibrotic drug development in NASH. There is a strong rationale for drug combinations to boost efficacy, and precision medicine strategies targeting key genetic modifiers of NASH are emerging. In this Perspective, we discuss why antifibrotic effects observed in NASH pharmacotherapy trials have been underwhelming and outline potential approaches to improve the likelihood of future clinical success.

Rate and determinants of antiviral treatment initiation for patients with HBeAg-negative chronic hepatitis B.

Most clinic attenders with chronic hepatitis B (CHB) are serum HBeAg-negative, and a minority will require suppressive antiviral treatment. Expert guidelines propose schedules for the monitoring of untreated patients, but the recommended frequency of patient review does not reflect recognised demographic determinants of HBeAg-negative chronic hepatitis. Also, the impact of patient ethnicity on risk has not been defined. The aim of our study was to determine the rates and determinants of antiviral treatment initiation in a large multi-ethnic cohort of CHB patients attending a single centre. We undertook a retrospective study using entirely electronic sources of patient information. Treatment initiation dates were identified from electronic pharmacy records. Crude and time-dependent statistical analyses were undertaken to identify rate and risk factors for treatment initiation. Treatment was initiated for 232/1256 (18.5%) patients with rates of 23.2% and 33.2% at 5 and 10 years. An increased risk of treatment was associated with male sex (RR 1.803), older age at presentation (RR 1.027 per year increase) and with non-Black ethnicity (RR 1.654). Patient sex, baseline age and ethnicity also determined risk for treatment in the subset of patients with normal serum ALT and low HBV DNA at baseline, though overall treatment rate in this group was low (only 2% per annum). Thus, patient demographics permit risk stratification for treatment initiation and could determine to a significant extent the frequency of review required for untreated HBeAg-negative patients. Black ethnicity is associated with a significant reduction in risk of treatment initiation.

Recent treatment advances and practical management of hepatitis D virus.

Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can only propagate in the presence of hepatitis B virus (HBV). Infection with both HBV and HDV frequently results in more severe disease than HBV alone, with higher instances of cirrhosis, liver failure and hepatocellular carcinoma (HCC). Thus, there is a need for effective treatment for HDV; however, currently approved treatment options are very limited both in terms of their efficacy and availability. This makes the management of HDV a challenge for physicians. In this review, we look at the background, diagnosis and treatment of HDV, informed by our hospital data, to set out the optimal management of HDV; we also explore novel treatment options for this disease.

Impaired lower limb muscle mass, quality and function in end stage liver disease: A cross-sectional study.

NEW FINDINGS: What is the central question of this study? To what extent does musculoskeletal impairment occur (i.e., muscle mass, quality and function) in patients with end stage liver disease (ESLD) by comparison to a healthy age/sex-matched control group? What is the main finding and its importance? Muscle mass, quality and function are impaired in patients with ESLD (compared to age/sex matched controls). Importantly, greater impairments were seen in lower limb compared to arm and trunk muscle groups. These findings may suggest that there should be greater consideration of muscle health in functionally relevant lower limb muscle groups. ABSTRACT: Sarcopenia is associated with reduced quality of life and increased mortality in patients with end stage liver disease (ESLD). Historically, sarcopenia identification in ESLD utilised L3 skeletal muscle index (SMI). There are few data on muscle quality and function within lower limb muscle groups with high functional relevance. The aim of this prospective case-control study was to evaluate the quadriceps muscle in patients with ESLD. Muscle mass and quality were evaluated using MRI (quadriceps anatomical cross sectional area (ACSA), quadriceps volume index, L3 SMI, quadriceps intermuscular adipose tissue (IMAT)), mid-arm muscle circumference (MAMC) and ultrasonography (vastus lateralis (VL) thickness and quadriceps ACSA). Muscle strength/function was assessed by handgrip strength, peak quadriceps isokinetic torque and chair rise time. Thirty-nine patients with ESLD (55 years, 61% male, 48% alcoholic related liver disease (ArLD), 71% Child-Pugh B/C) and 18 age/sex-matched healthy control participants (HC) were studied. Quadriceps mass was significantly reduced in ESLD versus HC (-17%), but L3 SMI and MAMC were unchanged. Quadriceps IMAT percentage was increased in ESLD (+103%). Handgrip strength (-15%), peak isokinetic torque (-29%), and chair rise time (+56%) were impaired in ESLD. Ultrasound measures of VL thickness (r = 0.56, r = 0.57, r = 0.42) and quadriceps ACSA (r = 0.98, r = 0.86, r = 0.67) correlated to MRI quadriceps ACSA, quadriceps volume and L3 SMI, respectively. Quadriceps muscle mass, quality, and function were impaired in patients with ESLD, whereas conventional assessments of muscle (L3 SMI and MAMC) highlighted no differences between ESLD and HC. Full evaluation of lower limb muscle health is essential in ESLD in order to accurately assess sarcopenia and target future interventions.

Effects of ketamine or dexmedetomidine on postoperative cognitive dysfunction after cataract surgery: A randomized controlled trial.

Background and Aims: Ketamine and dexmedet omidine have neuroprotective effects that may reduce the occurrence of postoperative cognitive dysfunction (POCD) when they are used by intravenous infusion in geriatric patients scheduled for cataract extraction. Methods: Ninety patients aged 65-85 years old, ASA physical status II and III, and scheduled for cataract extraction under peribulbar block were randomly distributed equally among three groups: control group, in which patients received normal saline; ketamine group, in which patients received 0.3 mg/kg/h of ketamine; and dexmedetomidine group, in which patients received 0.5 µg/kg/h of dexmedetomidine. Medications were administrated by intravenous infusion and started 10 min before the surgery and continued throughout the duration of surgery. The analysed parameters included the incidence of POCD (primary outcome) through composite score of neuropsychological testing at one week and 3 months after surgery, postoperative pain score, postoperative sedation score, changes in haemodynamic parameters, changes in intraocular pressure, and incidence of complications. Results: In comparison with control group, ketamine and dexmedetomidine groups exhibited a significant decline in number of patients who developed POCD (P < 0.0001), a decrease in the postoperative pain score 4 h after surgery (P = 0.038), and an increase in the postoperative Ramsay sedation Score (P = 0.0002, 0.0003, and 0.011), without significant changes in the vital parameters, intraocular tension, or incidence of complications. Ketamine and dexmedetomidine groups were comparable. Conclusion: Intravenous administration of ketamine or dexmedetomidine in elderly patients undergoing cataract surgery under peribulbar anesthesia significantly decreases the incidence of POCD.

Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans.

Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DILI at onset (NDO; n = 63) and follow-up (n = 42), and healthy volunteers (HV; n = 104). Area under the receiver operating characteristic curve (AUC) for cytoplasmic aconitate hydratase, argininosuccinate synthase, carbamoylphosphate synthase, fumarylacetoacetase, fructose-1,6-bisphosphatase 1 (FBP1) across cohorts achieved near complete separation (range: 0.94-0.99) of DO and HV. In addition, we show that FBP1, alone or in combination with glutathione S-transferase A1 and leukocyte cell-derived chemotaxin 2, could potentially assist in clinical diagnosis by distinguishing NDO from DO (AUC range: 0.65-0.78), but further technical and clinical validation of these candidate biomarkers is needed.

The Impact of Slice Interval and Equation on the Accuracy of Magnetic Resonance Image Estimation of Quadriceps Muscle Volume in End Stage Liver Disease.

Introduction: End stage liver disease (ESLD) is associated with loss of muscle mass and function, known as sarcopenia, which can increase the risk of complications of ESLD, hospitalization and mortality. Therefore, the accurate assessment of muscle mass is essential to evaluate sarcopenia in ESLD. However, manual segmentation of muscle volume (MV) can be laborious on cross-sectional imaging, due to the number of slices that require analysis. This study aimed to investigate the impact of reducing the number of slices required for MV estimation. Further, we aimed to compare two equations utilized in estimating MV (cylindrical and truncated cone). Methods: Thirty eight ESLD patients (23 males; 54.8 ± 10.7 years) were recruited from the Queen Elizabeth University Hospital Birmingham. A 3T MRI scan was completed of the lower limbs. Quadriceps MV was estimated utilizing 1-, 2-, 3-, and 4 cm slice intervals with both cylindrical and truncated cone equations. Absolute and relative error (compared to 1 cm slice interval) was generated for 2-, 3-, and 4 cm slice intervals. L3 skeletal muscle index (SMI) was also calculated in 30 patients. Results: Relative error increased with slice interval using the cylindrical (0.45 vs. 1.06 vs. 1.72%) and truncated cone equation (0.27 vs. 0.58 vs. 0.74%) for 2, 3, and 4 cm, respectively. Significantly, the cylindrical equation produced approximately twice the error compared to truncated cone, with 3 cm (0.58 vs. 1.06%, P < 0.01) and 4 cm intervals (0.74 vs. 1.72%, P < 0.001). Finally, quadriceps MV was significantly correlated to L3 SMI (r 2 = 0.44, P < 0.0001). Conclusion: The use of the truncated equation with a 4 cm slice interval on MRI offers an efficient but accurate estimation of quadricep muscle volume in ESLD patients.

Hepatitis B e antigen and e antibody in a multi-ethnic cohort of adult chronic hepatitis B virus patients followed at a single liver unit for a period of 20 years.

Hepatitis B virus e antigen (HBeAg) loss and the appearance of antibodies to HBeAg (anti-HBe) are favourable events in the history of chronic hepatitis B virus (CHB) infection. Most CHB patients have the HBeAg/anti-HBe profiles +/- or -/+, and little is published on the derivation or fate of the +/+ and -/- profiles. We have used electronically accessible patient data to study the HBeAg and anti-HBe profiles of a multi-ethnic cohort of adult HBV patients seen at a single centre over a period of more than 20 years. 3594 HBsAg-positive patients were identified and patients with viral coinfection or acute HBV infection were excluded. Cross-sectional and longitudinal analyses of HBeAg/anti-HBe status were undertaken. Compared with White or Black patients, Chinese and Asian patients are more likely to be HBeAg positive during child-bearing years. Patients with +/+ profile are likely to undergo HBeAg loss and seroconversion during relatively short follow-up. Chinese patients have a relatively increased rate of seroconversion. For HBeAg-positive patients, the risk of seroconversion diminishes with advancing age. Despite HBeAg loss, seroconversion is seldom observed after age 60 years. The proportion of HBV patients with -/- increases with age, and most acquire this profile by HBeAg loss but without antecedent seroconversion. -/- patients can lose HBsAg and develop anti-HBs. It was not possible to demonstrate a favourable impact of antiviral treatment on the rate of HBeAg seroconversion.

Acute-on-chronic liver failure (ACLF) in 2022: have novel treatment paradigms already arrived?

INTRODUCTION: Acute-on-chronic failure (ACLF) is a recognized syndrome in patients with chronic liver disease and is characterized by acute decompensation, organ failure(s), and a high short-term mortality. ACLF is often triggered by ongoing alcohol consumption, gastrointestinal bleeding and/or infections, and is pathophysiologically characterized by uncontrolled systemic inflammation coupled with paradoxical immunoparesis. Patients with ACLF require prompt and early recognition. Management requires extensive utilization of clinical resources often including escalation to intensive care. AREAS COVERED: Currently, there are no specific targeted treatments for established ACLF, and management revolves around treating underlying precipitants and providing organ support. In this article, we review the epidemiology and pathophysiology of ACLF and summarize recent advances in management strategies of this syndrome, focusing specifically on novel emerging therapies. EXPERT COMMENTARY: ACLF is a challenging condition with rapid clinical course, high short-term mortality and varying clinical phenotypes. Management of ACLF is broadly focused on supportive care often in an intensive care setting with liver transplantation proving to be an increasingly relevant and effective rescue therapy. This disease has clear pathogenesis and epidemiological burden, thus distinguishing it from decompensated cirrhosis; there is clear clinical need for the development of specific and nuanced therapies to treat this condition.

A UWB-Based Lighter-Than-Air Indoor Robot for User-Centered Interactive Applications.

Features such as safety and longer flight times render lighter-than-air robots strong candidates for indoor navigation applications involving people. However, the existing interactive mobility solutions using such robots lack the capability to follow a long-distance user in a relatively larger indoor space. At the same time, the tracking data delivered to these robots are sensitive to uncertainties in indoor environments such as varying intensities of light and electromagnetic field disturbances. Regarding the above shortcomings, we proposed an ultra-wideband (UWB)-based lighter-than-air indoor robot for user-centered interactive applications. We developed the data processing scheme over a robot operating system (ROS) framework to accommodate the robot's integration needs for a user-centered interactive application. In order to explore the user interaction with the robot at a long-distance, the dual interactions (i.e., user footprint following and user intention recognition) were proposed by equipping the user with a hand-held UWB sensor. Finally, experiments were conducted inside a professional arena to validate the robot's pose tracking in which 3D positioning was compared with the 3D laser sensor, and to reveal the applicability of the user-centered autonomous following of the robot according to the dual interactions.