Hepatitis B Immunoglobulin discontinuation in long‐term liver transplant patients

Background: Hepatitis B immunoglobulin (HBIG)-as a monotherapy or combined with nucleos(t)ide analogs (NUCs)-has effectively lowered Hepatitis B virus (HBV) reinfection after liver transplantation. However, it is associated with high costs and viral resistance. HBIG-free prophylaxis with novel NUCs (tenofovir, entecavir) composes a viable alternative. We evaluated reinfection rate, histological changes, and outcome associated with HBIG discontinuation. Methods: A retrospective analysis was performed of patients undergoing liver transplantation due to HBV-induced liver disease at our center since 1988. A controlled HBIG discontinuation was conducted between 2015 and 2017 in 65 patients. Recurrent infection was determined by HbsAg values. Fibrosis and inflammation were evaluated by routine biopsy. The survival of patients after HBIG discontinuation was compared to a control population on HBIG for prophylaxis. Results: From 1988 to 2013, 352 patients underwent liver transplantation due to HBV-induced liver disease. 169 patients could be included for analysis. 104 (51.5%) patients continued a prophylaxis containing HBIG. HBIG was discontinued in 65 (38.5%) patients in a controlled manner, maintaining an oral NUC. None of those patients showed HBV reinfection or graft dysfunction. No significant changes of inflammation grades (P = .067) or fibrosis stages (P = .051) were detected. The survival of patients after HBIG discontinuation was comparable to the control (P = .95). Conclusion: HBIG withdrawal under continuation of oral NUC therapy is safe and not related to graft dysfunction, based on blood tests and histology. HBIG-free prophylaxis is not associated with a worse outcome and displays a financial relief as well as a logistic simplification during long-term follow-up

Self‐limited HBV infection of the recipient does not reactivate after liver transplantation: Observations from a 30‐year liver transplant program

Background: A self-limited hepatitis B infection can reactivate in patients under immunosuppression or chemotherapy (reappearance of hepatitis B surface antigen (HBsAg) or HBV-DNA). Exact circumstances of HBV reactivation in patients undergoing liver transplantation (LT) for end-stage liver diseases (ESLD) unrelated to HBV are unknown, and recommendations on HBV prophylaxis remain unclear. Patients and methods: Among 1273 liver transplants, 168 patients with a self-limited HBV hepatitis B infection prior to LT were identified from our prospective liver transplant database. Patients with underlying chronic HBV infection and recipients of an anti-HBc-positive liver were not included in the analysis. Demographic, laboratory, serological, and virological data were analyzed retrospectively. Appearance of HBsAg or HBV-DNA was defined as reactivation. Results: The median follow-up after LT was 12.0 years (0.6-30.7 years). The rate of HBV reactivation was 0% independent of antiviral prophylaxis (n = 7; 4.2%), the etiology of ESLD, hepatitis C treatment, or the anti-HBs concentration. The overall patient survival with a history of a self-limited HBV infection before LT did not significantly differ from the rest of the cohort. Conclusion: Antiviral treatment with nucleos(t)ide analogues post-liver transplantation in order to prevent HBV reactivation in patients with a resolved self-limited hepatitis B infection prior to LT seems to be omittable since the main viral reservoir is removed by the hepatectomy. These findings may clarify the current uncertainty in the recommendations regarding the risk of HBV reactivation in patients with self-limited hepatitis B prior to LT

Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Ruiz JC, D'Afonseca V, Silva A, et al. Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains. PLoS ONE. 2011;6(4): e18551.Background: Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity. Methodology and Findings: We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer. Conclusions: These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829

Therapy and prophylaxis of viral hepatitis after liver transplant

In dieser Arbeit sollte ein Überblick über die Veränderungen der antiviralen Behandlung und Prophylaxe von Patienten nach Lebertransplantation auf dem Grund einer Hepatitis B oder C dargestellt werden. An unserem Zentrum wurden seit den 80ziger Jahren 372 HBV-assoziierte und über 500 HCV-assoziierte Lebertransplantation durchgeführt. Die Patienten erhielten allesamt eine enge Nachsorge über unsere spezialisierte Hochschulambulanz. Hauptanliegen in beiden Patientengruppen war stets, die Vermeidung von Sekundärkomplikationen durch eine virale Rekurrenz. Eine Besonderheit war die Möglichkeit einer histopathologischen Evaluation, da unsere Patienten im Rahmen der Nachsorge regelmäßigen Routinebiopsien zur Kontrolle des Transplantats unterzogen wurden. Eine Reinfektion mit HBV ließ sich bereits früh mittels HBIG deutlich reduzieren und letztlich durch den Einsatz moderner NUCs vollständig vermeiden. Dennoch war die Prävention dem Wandel der Zeit unterlegen und der Benefit bzw. die Auswirkungen einer Prophylaxe nicht von vornherein erkenntlich. Somit führten wir zum einen eine umfassende Evaluation unserer 30-jährigen Erfahrung in der Betreuung von HBV-Patienten durch, um eine praktikable, patientenorientierte und sichere Prophylaxe zu ermöglichen. Hier zeigte sich, dass zum einen die kontrollierte HBV-Reinfektion, die heutzutage durch den Einsatz von hoch-potenten NUCs als gut therapierbar gilt, die Prognose nicht schwerwiegend beeinträchtigt. Somit fiel die Entscheidung, Patienten weiterhin mit dem niedrig-potenteren Lamivudin kontrolliert zu schützen und nur im Falle einer Reinfektion die Substanz zu eskalieren. Eine weitere Neuerung aus den Untersuchungen zeigte, dass der Langzeit-Einsatz von HBIG als kombinierte Prophylaxe ebenfalls als nicht notwendig gilt. Das kontrollierte Absetzen führt jedoch bei den Patienten zu einer gesteigerten Lebensqualität und nicht zuletzt zur Reduktion der Arzt-Patientenkontakte und relativen Kostenersparnis. Im Gegensatz dazu bestand für die Hepatitis C keine geeignete Reinfektionsprophylaxe. Mit der Zulassung der DAAs nach 2014 eröffnete sich die Möglichkeit, die Patienten adäquat antiviral zu behandeln. Dies erfolgte schrittweise und teils außerhalb der medikamentösen Zulassungsbestimmungen, da initial wenige Daten zum Einsatz von DAAs in Transplantkohorten existierten. Dennoch schienen die Medikamente auch in dieser Randgruppe eine hohe Effizienz aufzuweisen, da innerhalb unserer behandelten Kohorte unabhängig vom Genotyp und vorbestehendem Fibrosegrad eine SVR von 100% erreicht werden konnte. Ribavirin spielt hierbei keine tragende Rolle mehr. Die HCV-assoziierten Sekundärkomplikationen, die Inflammation und Fibrose, wie auch die Nierenfunktion und der Diabetes mellitus profitierten signifikant von der antiviralen Behandlung. Dank der Sofosbuvir-basierten antiviralen Therapie konnte das Thema der HCV-Rekurrenz an unserer Klinik beendet werden

Hyperkalemia Following Parathyroidectomy in Patients with Renal Hyperparathyroidism—New Thresholds for Urgent Perioperative Dialysis

Parathyroidectomy (PTX) is a mainstay of treating secondary hyperparathyroidism (SHPT) in patients with kidney failure in order to reduce the incidence of cardiovascular events (CVE), increase overall survival and improve quality of life. Perioperative hyperkalemia may lead to devastating cardiac complications. Distinct preoperative thresholds for serum potassium levels (SPL) were defined, but neither their usefulness nor consecutive risks are understood. This study compared the results and efficacy of different clinical procedures in preventing or treating perioperative hyperkalemia, including postoperative urgent hemodialysis (UHD). Methods: Patients from Charité-Universitätsmedizin Berlin and Rheinland Klinikum Lukaskrankenhaus, Neuss, undergoing PTX due to SHPT between 2008 and 2018 were analyzed retrospectively with regard to demographic parameters, surgery specific conditions and perioperative laboratory results. Comparisons of patient values from both centers with focus on perioperative hyperkalemia and the need for UHD were performed. Results: A total of 251 patients undergoing PTX for SHPT were included (Neuss: n = 121 (48%); Berlin: n = 130 (52%)). Perioperative hyperkalemia (SPL ≥ 5.5 mmol/L) was noted in 134 patients (53%). UHD on the day of surgery was performed especially in patients with intraoperative hyperkalemia, in females (n = 40 (16%) vs. n = 27 (11%); p = 0.023), in obese patients (n = 27 (40%) vs. n = 50 (28%), p = 0.040) and more often in patients treated in Neuss (n = 42 (35%) vs. 25 (19%); p = 0.006). For patients treated in Neuss, the intraoperative hyperkalemia cut-off level above 5.75 mmol/L was the most predictive factor for UHD (n = 30 (71%) vs. n = 8 (10%); p 5.5 mmol/L measured in only one patient. Conclusion: Perioperative values could not predict postoperative hyperkalemia with the need for UHD. Previously defined cut-off levels for SPL should be reconsidered, especially for patients undergoing PTX. Early postoperative dialysis in patients with postoperative hyperkalemia can be performed with a low risk for complications and may be indicated for all patients with increased perioperative SPL

Textbook Outcome after Gastrectomy for Gastric Cancer Is Associated with Improved Overall and Disease-Free Survival.

(1) Background: The complexity of the perioperative outcome for patients with gastric cancer is not well reflected by single quality metrics. To study the effect of the surgical outcome on survival, we have evaluated the relationship between textbook outcome (TO)-a new composite parameter-and oncological outcome. (2) Methods: All patients undergoing total gastrectomy or trans-hiatal extended gastrectomy for gastric cancer with curative intent between 2017 and 2021 at our institution were included. TO was defined by negative resection margins (R0); collection of ≥25 lymph nodes; the absence of major perioperative complications (Clavien-Dindo ≥ 3); the absence of any reintervention; absence of unplanned ICU re-admission; length of hospital stay 4 (p = 0.034, OR 2.844, CI 1.079-7.493) were significant factors affecting DFS upon univariate analysis. In multivariate analysis, CCI > 4 (p = 0.035, OR 2.605, CI 0.983-6.905) was significantly associated with DFS. (4) Conclusions: We identified patient- and procedure-related factors influencing TO. Importantly, achieving TO is strongly associated with improved long-term survival in gastric cancer patients and merits further focus on surgical quality improvement efforts

Discontinuation of Passive Immunization Is Safe after Liver Transplantation for Combined HBV/HDV Infection

Patients after LT due to combined HBV/HDV infection are considered to be high-risk patients for recurrence of hepatitis B and D. To date, life-long prophylaxis with hepatitis B immunoglobulin (HBIG) and replication control with nucleos(t)ide analogs (NA) remains standard. We examined the course of 36 patients that underwent liver transplantation from 1989 to 2020 for combined HBV/HDV-associated end-stage liver disease in this retrospective study. Seventeen patients eventually discontinued HBIG therapy for various reasons. Their graft function, histopathological findings from routine liver biopsies and overall survival were compared with those that received an unaltered NA-based standard regimen combined with HBIG. The median follow-up was 204 and 227 months, respectively. The recurrence of HBV was 25% and did not differ between the groups of standard reinfection prophylaxis NA/HBIG (21.1%) and HBIG discontinuation (29.4%); (p = 0.56). No significant differences were found regarding the clinical course or histopathological aspects of liver tissue damage (inflammation, fibrosis, steatosis) between these two groups. Overall, and adjusted survival did not differ between the groups. Discontinuation of HBIG in stable patients after LT for combined HBV/HDV did not lead to impaired overall survival or higher recurrence rate of HBV/HDV infection in this long-term follow-up. Therefore, the recommendation of the duration of HBG administration must be questioned. The earliest time of discontinuation remains unclear

Surgical Approach to Liver Metastases in GEP-NET in a Tertiary Reference Center

Indications for liver resection in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) vary from liver resection with curative intent to tumor debulking or tissue sampling for histopathological characterization. With increasing expertise, the number of minimally invasive liver surgeries (MILS) in GEP-NET patients has increased. However, the influence on the oncological outcome has hardly been described. The clinicopathological data of patients who underwent liver resection for hepatic metastases of GEP-NET at the Department of Surgery, Charité—Universitätsmedizin Berlin, were analyzed. Propensity score matching (PSM) was performed to compare MILS with open liver surgery (OLS). In total, 22 patients underwent liver surgery with curative intent, and 30 debulking surgeries were analyzed. Disease-free survival (DFS) was longer than progression-free survival (PFS) (10 vs. 24 months), whereas overall survival (OS) did not differ significantly (p = 0.588). Thirty-nine (75%) liver resections were performed as OLS, and thirteen (25%) as MILS. After PSM, a shorter length of hospital stay was found for the MILS group (14 vs. 10 d, p = 0.034), while neither DFS/PFS nor OS differed significantly. Both curative intended and cytoreductive resection of hepatic GEP-NET metastases achieved excellent outcomes. MILS led to a reduced length of hospital, while preserving a good oncological outcome