Enhancing linkage to care for hepatitis B, D, and C patients: A retrospective-prospective study.

BACKGROUND: The WHO has set a goal to decrease viral hepatitis-related fatalities by 65% by 2030. AIMS: To locate and retrieve to care all individuals diagnosed with hepatitis B, D or C, and investigate why they were not linked to appropriate medical management. METHODS: We conducted a retrospective-prospective search for patients with hepatitis B, D or C virus (HBV, HDV and HCV) infection in the central laboratory database of the Barcelona northern health area (catchment population, 450,000). We reviewed records and contacted candidates for retrieval who were offered a specialist medical visit. RESULTS: We reviewed records of 3731 patients with viral hepatitis (January 2019-December 2022): 1763 HBsAg+, 69 anti-HDV+ and 1899 HCV-RNA+. Among these, 644 (37%) HBV, 20 (29%) HDV and 1116 (56%) HCV patients were not currently linked to care. The proportion of patients receiving appropriate care was higher in HBV and HDV (p < 0.0001), and a higher percentage of unlinked hepatitis C patients had low life expectancy/comorbidities (39%; p < 0.0001). After implementing the linkage strategy, 254 HBV, 16 HDV and 54 HCV patients were successfully reintegrated into care. Among 1780 patients requiring linkage, 638 (35.8%) had moved to another health area or were missing essential contact data. CONCLUSIONS: Among patients with viral hepatitis who required appropriate specialist care and were eligible for contact, 64% with HBV, 100% with HDV and 27% with HCV were successfully reintegrated into care. Overall, 324 (47.2%) eligible patients were linked to care, indicating the success of this strategy.

Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir.

BACKGROUND: Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). METHODS: Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. RESULTS: In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non-GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. CONCLUSION: SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first-line therapy with SOF/VEL were not associated with lower SVRs.

Acute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome.

Acute kidney injury (AKI) in patients with cirrhosis is a diagnostic challenge due to multiple and sometimes overlapping possible etiologies. Many times, diagnosis cannot be made based on case history, physical examination or laboratory data, especially when the nephrologist is faced with AKI with a hemodynamic basis, such as hepatorenal syndrome. In addition, the guidelines still include generalized recommendations regarding withdrawal of diuretics and plasma volume expansion with albumin for 48 h, which may be ineffective and counterproductive and may have iatrogenic effects, such as fluid overload and acute cardiogenic pulmonary edema. For this reason, the use of new tools, such as hemodynamic point-of-care ultrasound (PoCUS), allows us to phenotype volume status more accurately and ultimately guide medical treatment in a noninvasive, rapid and individualized manner.

Rituximab is a safe and effective alternative treatment for patients with autoimmune hepatitis: Results from the ColHai registry.

BACKGROUND AND AIMS: Small series suggest that rituximab could be effective as treatment for autoimmune hepatitis (AIH), although data are scarce. We aimed to evaluate the efficacy and safety of rituximab in different cohorts of patients with AIH. METHODS: Multicentre retrospective analysis of the 35 patients with AIH and its variant forms treated with rituximab and included in the ColHai registry between 2015 and 2023. RESULTS: Most patients were female (83%), 10 (29%) had cirrhosis and four (11.4%) variant forms of AIH. Indication for rituximab were as follows: 14(40%) refractory AIH, 19(54%) concomitant autoimmune or haematological disorder, 2(6%) intolerance to prior treatments. In three (9%) subjects with a concomitant disorder, rituximab was the first therapy for AIH. Overall, 31 (89%) patients achieved or maintained complete biochemical response (CBR), including the three in first-line therapy. No difference in CBR was observed according to rituximab indication (refractory AIH 86% vs. concomitant disorders 90%, p = .824) or cirrhosis (80% vs. 92%, p = .319). Rituximab was associated with a significant reduction in corticosteroids (median dose: prior 20 vs. post 5 mg, p < .001) and the discontinuation of ≥1 immunosuppressant in 47% of patients. Flare-free rate at 1st, 2nd and 3rd year was 86%, 73% and 62% respectively. Flares were not associated with the development of liver failure and were successfully managed with repeated doses of rituximab and/or increased corticosteroids. Three (9%) patients experienced infusion-related adverse events (1 anaphylaxis and 2 flu-like symptoms) and five (14%) infections. CONCLUSION: Rituximab is safe and effective in patients with refractory AIH and those treated due to concomitant autoimmune or haematological disorders.

An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor-induced liver injury.

BACKGROUND: There are few data on corticosteroids (CS)-sparing strategies for checkpoint inhibitor (ICI)-induced liver injury (ChILI). AIM: We aimed to assess the performance of a 2-step algorithm for severe ChILI, based on ICI temporary discontinuation (step-1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step-2). METHODS: Prospective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening. RESULTS: From 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti-PD1, 8(18.2%) anti-PD-L1, 3(6.8%) anti-CTLA-4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step-1) and 8/22 (36.4%) based on the degree of necroinflammation (step-2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non-improvement patients after ICI discontinuation. CD8+ HLA-DR expression (p = 0.028), central memory (p = 0.046) were lower in CS-free managed subjects, but effector-memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS-free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed. CONCLUSIONS: An algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI.

Proprioceptive innervation of the human lips.

The objective of this study was to analyze the proprioceptive innervation of human lips, especially of the orbicularis oris muscle, since it is classically accepted that facial muscles lack typical proprioceptors, that is, muscle spindles, but recently this has been doubted. Upper and lower human lips (n = 5) from non-embalmed frozen cadavers were immunostained for detection of S100 protein (to identify nerves and sensory nerve formations), myosin heavy chain (to label muscle fibers within muscle spindles), and the mechano-gated ion channel PIEZO2. No muscle spindles were found, but there was a high density of sensory nerve formations, which were morphologically heterogeneous, and in some cases resemble Ruffini-like and Pacinian sensory corpuscles. The axons of these sensory formations displayed immunoreactivity for PIEZO2. Human lip muscles lack typical proprioceptors but possess a dense sensory innervation which can serve the lip proprioception.

Integrating viral hepatitis management into the emergency department: A further step towards viral hepatitis elimination.

Background & Aims: Many people with HCV and HBV infection are unaware of their condition, particularly at-risk and vulnerable populations who face barriers for screening and linkage to care. Emergency departments are often their only point of contact with the health system. Methods: This is a prospective study investigating HBsAg and HCV antibody testing, with reflex testing for HDV antibodies and HCV RNA, in adults attending an emergency department and requiring a blood test. Positive cases were linked to care. A cost-effectiveness analysis was performed. Results: From February 2020 to February 2022, a total of 17,560 individuals were screened. HBsAg was detected in 91 (0.5%), HCV RNA in 128 (0.7%), and HDV antibodies in two (0.01%) individuals. Nearly 40% of positive cases were unaware of their condition. Linkage to care was achieved in 42 of 56 HBsAg-positive and 45 of 69 HCV RNA-positive participants who were candidates for referral. HCV and HBV screening vs. no screening yielded 1.06 and 0.42 additional quality-adjusted life-years, respectively, with incremental cost-utility ratios of €7,629 and -€147 per quality-adjusted life-year gained, respectively, and proved even more cost-effective in patients with hepatitis C aged 40-70 years. Conclusions: On emergency department screening for hepatitis B, C, and D in Barcelona, the prevalence of HBsAg was 0.5% and HCV RNA 0.7%, approximately threefold higher than that observed in the general population. This strategy diagnosed patients with active HCV infection and no risk factors, who would not have been screened according to the current recommendations. Screening and linkage to care of viral hepatitis is cost-effective in this setting. Impact and implications: We evaluated the performance and cost-effectiveness of a viral hepatitis screening programme implemented in an emergency department, which aimed to identify and link to care people living with hepatitis B and C. Our findings reveal a threefold higher prevalence of hepatitis B and C than in the general Spanish population, possibly attributable to the role of the emergency department as the main healthcare gateway for vulnerable populations, who have a higher prevalence of viral hepatitis. Risk factors for viral hepatitis could not be identified in most people living with hepatitis B and C attending the emergency department; hence, screening beyond risk factors should be considered in hepatitis detection strategies. Emergency department screening is cost-effective for hepatitis C and is a cost-saving strategy for hepatitis B in our setting. These data should inform future updates to clinical guidelines.

Assessing the rate of non-linkage to care and identifying barriers in individuals living with hepatitis B. Results of the LINK-B study.

BACKGROUND & AIMS: Hepatitis B infection is the most frequent cause of chronic hepatitis and liver cancer worldwide. Active searching for individuals with chronic hepatitis B has been proposed as a strategy to achieve the elimination of this virus. The primary aim of this study was to link to specialists HBsAg-positive individuals detected in a laboratory database and to characterize individuals who were not linked to care. METHODS: We performed a retrospective-prospective evaluation of all HBsAg-positive serum samples identified in the central laboratory of the Northern Barcelona area between January 2018 and June 2022. After reviewing the patients' clinical charts, all those not linked to care were given an appointment with a specialist. RESULTS: Medical records of 2765 different HBsAg-positive serum samples were reviewed and 2590 individuals were identified: 844 (32.6%) were not linked to a specialist, 653 were candidates for linkage, and 344 attended the specialist visit. The two main reasons why they were not under specialist care were administrative issues, such as living in another region (12.1%) and lacking contact details (4.1%), and low life expectancy (2.8%). Individuals who did not attend their scheduled visit were mainly young [38.1 ± 12.9 vs. 44.0 ± 14.0 (p < .001)], non-White European [75.3% vs. 58.1% (p < .001)] and men [70.7% vs. 56.4% (p < .001)]. CONCLUSIONS: One in every three HBsAg-positive individuals in our setting was not currently under specialist care. Of particular note, half of them had never attended a specialist consultation, an essential step for evaluating the disease and starting therapy in some countries.

Exploring somatosensory innervation of the human lip: A focus on the vermilion.

BACKGROUND: The lips are a vital component of the face and are densely innervated to perform various functions. The lip edges are covered with mucocutaneous tissue called vermilion which is particularly receptive to touch and temperature. The aim of this study was to investigate the somatosensory innervation of human lips, focusing on sensory corpuscles and the presence of mechano-gated (ASIC2, PIEZO2, and TRPV4) and thermosensing (TRPV1, TRPM2, and RPM8) ion channels within them. METHODS: Twelve intact lips (6 upper and 6 lower) were obtained from non-embalmed frozen cadavers (five females and seven males) with an age range of 60-80 years. The specimens were divided into three zones (medial, lateral, and median). The morphotypes of sensory corpuscles and their immunohistochemical profile was analysed. The occurrence of ion channels involved in mechanosensation and temperature detection was examined using various antibodies. Sensory corpuscle density was quantified in vermilion sections, and statistical analyses were conducted to assess differences between the upper and lower lips, as well as between females and males (p < 0.05). RESULTS: Different morphotypes of sensory corpuscles were identified: Ruffini-like associated with hair follicles, Meissner and glomerular corpuscles in the vermilion, and less classifiable sensory corpuscles within the mucosa. The density of sensory corpuscles in the vermilion was higher in the upper lip than in the lower lip; glomerular corpuscles predominated in the medial and median segments, whereas Meissner corpuscles were more abundant in the lateral segment. No sex-related differences were observed in the density or distribution of the two main corpuscular morphotypes. In contrast, the axons of both the glomeruli and Meissner corpuscles regularly displayed ASIC2 and PIEZO2 immunoreactivity, whereas immunoreactivity for TRPV1, TRPV4, TRPM2, and TRPV8 was absent. CONCLUSIONS: These results demonstrate that the sensory corpuscles of the vermilion are a mixture of those typical of glabrous skin mucocutaneous tissues. The presence of PIEZO2 and ASIC2 in their axons suggests that these sensory corpuscles function as mechanosensors.

Effect of supramucosal height of a scan body and implant angulation on the accuracy of intraoral scanning: An in vitro study.

STATEMENT OF PROBLEM: Intraoral scanners (IOSs) provide a digital alternative to conventional implant impression techniques. However, the effect of the supramucosal height of the scan body and implant angulation on the accuracy of IOSs remains unclear. PURPOSE: The purpose of this in vitro study was to measure the impact of the supramucosal height of the scan body and implant angulation on the accuracy (trueness and precision) of intraoral digital implant scans in partially edentulous models. MATERIAL AND METHODS: Two maxillary partially edentulous casts with 4 implant analogs were fabricated, 1 with 4 parallel implants (P-groups) and 1 with 2 implants distally inclined 18 degrees (A-groups). An implant scan body was positioned on each implant analog (CARES RC Mono Scanbody). For each cast, 3 subgroups were determined based on the soft tissue moulage fabricated for each reference cast exposing 3 mm (P-3 and A-3 subgroups), 5 mm (P-5 and A-5 subgroups), and 7 mm (P-7 and A-7 subgroups) of the implant scan bodies. The 2 reference casts were registered by using a coordinate measurement machine and desktop scanner (7 Series Dental Wings) and then scanned using an IOS (TRIOS 4) (n=15). Linear and angular discrepancy values and root mean square (RMS) error values between the implant scan bodies measured on the reference and experimental scans were computed with an inspection software program (Geomagic). Mann-Whitney U tests with Bonferroni correction were applied for planned comparisons (α=.05/9 ≈ .006). RESULTS: For linear discrepancies, statistically significant differences were found between groups P-3 and A-3 (P=.004) and between P-7 and A-7 (P=.005). For angular discrepancies, statistically significant differences were found between groups A-3 and A-5 (P=.002) and between P-7 and A-7 (P=.003). The RMS error analysis found no statistically significant differences among the groups. CONCLUSIONS: Implant angulation of 18 degrees did not significantly affect the accuracy of the intraoral scans in terms of 6 of the 9 planned comparisons, although the angled groups had lower mean values. Also, the supramucosal height of the scan body did not significantly affect the accuracy of the intraoral scans in terms of 17 of the 18 planned comparisons. Results may vary with different implant scan body designs.