Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

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.

Liver Disease and Cell Therapy: Advances Made and Remaining Challenges.

The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for alternative therapies. Mesenchymal stromal cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties have therefore emerged as a promising therapeutic agent in treating inflammatory liver disease. Significant strides have been made in exploring their biological activity. Clinical application of MSC has shifted the paradigm from using their regenerative potential to one which harnesses their immunomodulatory properties. Reassuringly, MSCs have been extensively investigated for over 30 years with encouraging efficacy and safety data from translational and early phase clinical studies, but questions remain about their utility. Therefore, in this review, we examine the translational and clinical studies using MSCs in various liver diseases and their impact on dampening immune-mediated liver damage. Our key observations include progress made thus far with use of MSCs for clinical use, inconsistency in the literature to allow meaningful comparison between different studies and need for standardized protocols for MSC manufacture and administration. In addition, the emerging role of MSC-derived extracellular vesicles as an alternative to MSC has been reviewed. We have also highlighted some of the remaining clinical challenges that should be addressed before MSC can progress to be considered as therapy for patients with liver disease.

Outcomes of incoming and outgoing second opinions from a UK liver transplant centre.

OBJECTIVE: Second transplant centre opinions (STCOs) for patients declined for liver transplantation are infrequent. We aimed to identify STCOs outcomes from a tertiary transplant centre. DESIGN: Referrals between 2012 and 2020 to Birmingham Unit were reviewed. Incoming: all referrals from out-of-region centres were collated. Outgoing: patients not listed in Birmingham were reviewed to identify referrals for STCOs to the other UK centres (A-F). RESULTS: 2535 patients were assessed for liver transplantation during the study period. Incoming: among 1751 referrals, 23 STCOs (17 unit A, 3 unit B, 1 unit C, 1 unit D and 1 unit E) were provided by Birmingham. Of the STCOs, 13/23 (57%) patients remained unsuitable for transplantation. Therefore, 10/23 (43%) underwent a second liver transplant assessment, of whom five (50%) were still deemed unsuitable, three (30%) listed (one transplanted) and two (20%) died preassessment. Outgoing: among 426 patients not listed, eight (1.8%) patients were referred for STCO (4 unit E, 2 unit B, 1 unit D, 1 unit A). Three (38%) were listed, two (25%) were assessed and declined, two (25%) were unsuitable for assessment and one (12.5%) died while waiting. Combining incoming and outgoing Birmingham STCOs (n=31), six (19%) of STCOs were listed in a second centre. CONCLUSION: Second transplant centre opinions are rare with the majority still deemed unsuitable for liver transplantation. This highlights potential resource implications especially when undergoing a full second formal assessment. A streamlined STCO process with sharing of investigations and use of telemedicine in appropriate patients may allow for greater transparency, quicker decision making and less use of labour-intensive resources.

Sequential Cohort Analysis After Liver Transplantation Shows de Novo Extended Release Tacrolimus Is Safe, Efficacious, and Minimizes Renal Dysfunction.

The use of once-daily extended-release tacrolimus (ERT) is associated with improved long-term graft and patient survival when compared with twice-daily tacrolimus (BDT), but the underlying reasons for differential survival are unclear. The aim of the study was to compare clinical outcomes known to impact on posttransplant survival for de novo BDT and ERT in liver transplantation (LT) recipients. METHODS: We conducted a single-center, prospective sequential cohort analysis of adult patients undergoing LT during a change in protocol from de novo BDT to ERT, with a 6-month post-LT follow-up. RESULTS: A total of 160 transplanted patients were evaluated; 82 were in the BDT group and 78 were in the ERT group. The cohorts were matched for standard variables and a similar proportion in each group received induction interleukin-2 receptor antibody (36% and 31%). There were no significant differences in the measured outcomes of patient and graft survival, biopsy-proven acute rejection episodes, post LT diabetes, and toxicity. A significantly lower number of patients developed chronic kidney disease Stage3-4 in the ERT cohort compared with BDT cohort. In patients with pre-LT renal dysfunction who received antibody induction, estimated glomerular filtration rate decreased significantly in the BDT but not the ERT group. CONCLUSIONS: We show that once-daily ERT is as safe and efficacious as BDT in de novo LT but optimally conserves renal function post-LT.

Risk factors for obstetric anal sphincter injuries (OASIS) and the role of episiotomy: A retrospective series of 496 cases.

OBJECTIVE: The objective of this study was to determine the prevalence and identify risk factors for obstetric anal sphincter injuries (OASIS), and to determine the prevalence of episiotomy and whether it is protective for the posterior perineum. STUDY DESIGN: This is a retrospective case-control study carried out in a level 2 maternity unit and a level 3 maternity unit between 1 January 2006 and 31 December 2015. The sample population included all vaginal deliveries at term of a living singleton foetus in cephalic presentation. The case group comprised patients with an OASIS. The control group comprised patients without OASIS. Statistical analysis was subdivided into descriptive and inferential parts. RESULTS: 42,626 patients were included in the study of whom 496 were cases of OASIS, i.e. a rate of 1.2%. The overall episiotomy rate was 10.0%, which reflects a restrictive practice. Episiotomy doesn't appear to be a statistically significant protective factor for OASIS (OR=0.89-95%CI [0.68-1.16]). The principal independent risk factors for OASIS were nulliparity (ORa=4.19-95%CI [3.03-5.84] - p<0.001), previous caesarean (ORa=5.59-95%CI [3.68-8.44] - p<0.001), uterine fundal height greater than 32cm (ORa=1.35-95%CI [1.03-1.77] - p=0.03), gestational or pre-pregnancy diabetes (ORa=1.76-95%CI [1.22-2.46] - p=0.002), birthweight of more than 3500g (ORa=1.48-95%CI [1.17-1.87] - p=0.001), assisted delivery (ORa=1.81-95%CI [1.18-2.86] - p=0.007), and use of a second instrument or obstetrical manoeuvre (ORa=1.93-95%CI [1.05-3.30] - p=0.02). CONCLUSION: Episiotomy doesn't appear to be a statistically significant protective factor on the perineal prognosis. A deeper understanding of the factors which promote OASIS and greater awareness of them would improve the perineal prognosis of parturient women.

Time to endoscopy for acute upper gastrointestinal bleeding: Results from a prospective multicentre trainee-led audit.

Background: Endoscopy within 24 h of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24 h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups. Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p = 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p = 0.004), but not 30-d mortality (p = 0.344). Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

Cesarean Scar Ectopic Pregnancy: Laparoscopic Resection and Total Scar Dehiscence Repair.

STUDY OBJECTIVE: To illustrate a laparoscopic technique for the resection of cesarean scar ectopic pregnancy, associated with isthmocele repair. DESIGN: Case report (Canadian Task Force classification III). SETTING: A tertiary referral center in Strasbourg, France. BACKGROUND: Cesarean scar pregnancy is a rare form of ectopic pregnancy. The major risk of this type of pregnancy is the early uterine rupture with massive, sometimes life-threatening, bleeding. Thus, active management of these pregnancies starting immediately after diagnosis is crucial. Therapeutic options can be medical, surgical, or a combination. Numerous case reports or case series can be found in the literature, but there are few clinical studies, which are difficult to conduct because of case rarity and inconclusiveness. A 2016 meta-analysis that included 194 articles published between 1978 and 2014 (126 case reports, 45 cases series, and 23 clinical studies) concluded that hysteroscopy or laparoscopic hysterotomy seems to be the best first-line approach to treating cesarean scar ectopic pregnancy, with uterine artery embolization reserved for significant bleeding and/or a high suspicion index for arteriovenous malformation [1]. There is no consensus on the treatment of reference, however. PATIENT: The case involves a 38-year-old primiparous women who underwent a cesarean section delivery in 2010 and who was diagnosed by ultrasound scan at 7 weeks gestation with cesarean scar ectopic pregnancy, which was confirmed by pelvic magnetic resonance imaging. The patient initially received medical treatment with 2 intramuscular injections of methotrexate and one local intragestational injection of KCl. Her initial human chorionic gonadotropin (hCG) level was 82 000 IU/L. Rigorous weekly biological and ultrasound monitoring revealed an involution of the ectopic pregnancy associated with decreasing hCG. No bleeding or infectious complications occurred during this period. After 10 weeks of monitoring, her hCG had stabilized at 300 IU/L, and a residual image persisted next to the cesarean scar, and thus surgical treatment was considered. INTERVENTION: This video illustrates the laparoscopic resection of a cesarean scar ectopic pregnancy associated with isthmocele repair. The originality of this video lies in the fact that it is the first demonstration of the laparoscopic treatment of total caesarean scar dehiscence. MEASUREMENTS AND MAIN RESULTS: The total operative time was 180 minutes. First, hysteroscopic evaluation revealed the cesarean scar dehiscence and the posterior pole of the ectopic pregnancy. Then the diagnosis of cesarean scar ectopic pregnancy was confirmed laparoscopically. The utero-ombilical truncs were clamped bilaterally. Complete enucleation of pregnancy was achieved after dissection of the vesicouterine peritoneum. Isthmocele repair was performed with closure in 2 planes. A blue dye test confirmed the tightness of the stitches. The utero-ombilical truncs were unclamped, and antiadhesion gel was applied to the new uterine scar [1]. The operation was performed successfully without complications. Intraoperative blood loss was <100 mL. The patient was discharged on postoperative day 3. No immediate complications were noticed. At 1 month after the intervention, ultrasound was normal. CONCLUSION: Surgical management of caesarean scar ectopic pregnancy with total dehiscence of hysterotomy can be performed safely and efficiently under laparoscopy.

A peer-led teaching initiative for foundation doctors.

BACKGROUND: Peer teaching has been used informally throughout the history of medical education. Formal studies within the medical student and allied health care professional communities have found it to be a popular, and highly effective, method of teaching. CONTEXT: Newly qualified doctors are currently an underused resource in terms of teaching one another. INNOVATION: A committee, made up of newly qualified doctors and postgraduate education staff, was established. Using only a few resources, this committee organised regular, peer-led tutorials and used educational needs assessment tools, such as questionnaires, to make improvements to early postgraduate training. IMPLICATION: A realistic and well-received intervention to improve the teaching of newly qualified doctors, which is feasible in the modern, busy health care setting. Other institutions may find this method and its resources valuable. Newly qualified doctors are currently an underused resource in terms of teaching one another.