Liver Transplantation for Hepatocarcinoma: Results over Two Decades of a Transplantation Programme and Analysis of Factors Associated with Recurrence.

BACKGROUND: In recent years, many studies have attempted to develop models to predict the recurrence of hepatocarcinoma after liver transplantation. METHOD: A single-centre, retrospective cohort study analysed patients receiving transplants due to hepatocarcinoma during the 20 years of the transplant programme. We analysed patient survival, hepatocarcinoma recurrence and the influence of the different factors described in the literature as related to hepatocarcinoma recurrence. We compared the results of previous items between the first and second decades of the transplantation programme (1995-2010 and 2010-2020). RESULTS: Of 265 patients, the patient survival rate was 68% at 5 years, 58% at 10 years, 45% at 15 years and 34% at 20 years. The overall recurrence rate of hepatocarcinoma was 14.5%, without differences between periods. Of these, 54% of recurrences occurred early, in the first two years after transplantation. Of the parameters analysed, an alpha-fetoprotein level of >16 ng/mL, the type of immunosuppression used and the characteristics of the pathological anatomy of the explant were significant. A trend towards statistical significance was identified for the number of nodules and the size of the largest nodule. Logistic regression analysis was used to develop a model with a sensitivity of 85.7% and a specificity of 35.7% to predict recurrences in our cohort. Regarding the comparison between periods, the survival and recurrence rates of hepatocarcinoma were similar. The impact of the factors analysed in both decades was similar. CONCLUSIONS: Most recurrences occur during the first two years post-transplantation, so closer follow-ups should be performed during this period, especially in those patients where the model predicts a high risk of recurrence. The detection of patients at higher risk of recurrence allows for closer follow-up and may, in the future, make them candidates for adjuvant or neoadjuvant systemic therapies to transplantation.

T3-T4 index as a prognostic marker of response to biological treatments in elderly patients with inflammatory bowel disease.

Following the growing trend of trying to individualise treatment in inflammatory bowel disease and in view of the challenge posed by elderly patients requiring biologic treatments, we have conducted a study in our centre to assess the T3/T4 index as a predictor of response to biologic treatments in elderly patients.

Acute liver failure secondary to malignant infiltration: A single center experience.

Acute liver failure (ALF) requires early and very precise treatment decisions for a diagnosis that is not often easy and may lead to erroneous decisions. Accordingly, we undertook a review of ALF secondary to malignant infiltration given the rarity of the condition, plus its singularity and therapeutic implications. This review should aid in establishing future frameworks for action. Analyze cases of ALF secondary to malignant infiltration in our center during the last 5 years and review the literature. We undertook a retrospective review of all cases of ALF due to malignant infiltration in our center between January 2015 and December 2019. Data were recorded on demographic characteristics, clinical presentation, type of tumor, diagnostic techniques used, treatment and evolution. We also undertook a literature review on the subject and compared the results. AFL secondary to malignant infiltration was diagnosed in five patients, four women and one man with a median age 58 years. The most common clinical presentation was jaundice. Three cases were due to infiltration by hematological tumors (non-Hodgkin lymphoma and histiocytosis), one a cholangiocarcinoma and one lung cancer. In all cases a liver biopsy was required for diagnosis, this being conclusive in four cases; diagnosis in the non-conclusive case was by analysis of the hepatectomy sample after transplantation. Three patients died due to AFL in a mean of 13.8 days, another died 5 months after diagnosis as a consequence of the tumor while the patient with a diagnosis of non-Hodgkin lymphoma and transplant recipient remains alive after a follow-up of 6 years and after receiving chemotherapy. AFL due to malignant infiltration is a very unusual condition but with a high rate of mortality. It requires a rapid and precise diagnosis given the relevant treatment options.

Microbiota diversity in nonalcoholic fatty liver disease and in drug-induced liver injury.

The gut microbiota could play a significant role in the progression of nonalcoholic fatty liver disease (NAFLD); however, its relevance in drug-induced liver injury (DILI) remains unexplored. Since the two hepatic disorders may share damage pathways, we analysed the metagenomic profile of the gut microbiota in NAFLD, with or without significant liver fibrosis, and in DILI, and we identified the main associated bacterial metabolic pathways. In the NAFLD group, we found a decrease in Alistipes, Barnesiella, Eisenbergiella, Flavonifractor, Fusicatenibacter, Gemminger, Intestinimonas, Oscillibacter, Parasutterella, Saccharoferementans and Subdoligranulum abundances compared with those in both the DILI and control groups. Additionally, we detected an increase in Enterobacter, Klebsiella, Sarcina and Turicibacter abundances in NAFLD, with significant liver fibrosis, compared with those in NAFLD with no/mild liver fibrosis. The DILI group exhibited a lower microbial bacterial richness than the control group, and lower abundances of Acetobacteroides, Blautia, Caloramator, Coprococcus, Flavobacterium, Lachnospira, Natronincola, Oscillospira, Pseudobutyrivibrio, Shuttleworthia, Themicanus and Turicibacter compared with those in the NAFLD and control groups. We found seven bacterial metabolic pathways that were impaired only in DILI, most of which were associated with metabolic biosynthesis. In the NAFLD group, most of the differences in the bacterial metabolic pathways found in relation to those in the DILI and control groups were related to fatty acid and lipid biosynthesis. In conclusion, we identified a distinct bacterial profile with specific bacterial metabolic pathways for each type of liver disorder studied. These differences can provide further insight into the physiopathology and development of NAFLD and DILI.

Experience in the treatment of esophageal anastomosis dehiscence using self-expanding metallic prosthesis

Introduction: esophageal anastomosis dehiscence is a serious complication after esophageal cancer surgery with high mortality risk. One of the treatment options is self-expanding esophageal prostheses. Our aim was to evaluate the outcome of esophageal prostheses in the management of suture dehiscences after oncologic surgery.Material and methods: we performed a descriptive and retrospective study with patients diagnosed with esophageal anastomosis fistula or dehiscence treated by esophageal prosthesis between the years 2015 and 2021. We considered technical success as the correct positioning of the prosthesis with visualization of anastomotic leak closure after release of the prosthesis during endoscopy, and clinical success the resolution of dehiscence after removal of the prosthesis 8 weeks after positioning.Results: technical success was 95% and clinical success 89%.Conclusion: in our center, esophageal prostheses are a treatment option for fistulas and anastomotic dehiscence after surgery with a high success rate and few complications. (AU)

Experience in the treatment of obstructive colorectal cancer with self-expandable colon prosthesis in a tertiary hospital.

Colorectal cancer is one of the most frequent neoplasms, with an increasing incidence in recent years. Intestinal obstruction is present at the time of diagnosis in 10-30% of patients. The aim of our study is to describe our experience in the use of colonic SEMS in the treatment of colonic stenosing neoplasia. For this purpose, we retrospectively evaluated the 92 patients treated with self-expandable metallic prostheses in our hospital between 2016 and 2021. In 66.3% of patients the prosthesis placement was bridge to curative surgery and in 33.7% with palliative attitude. The stenosis location was differentiated: rectum (2.1%), rectosigmoid junction (20.7%), sigma (58.7%), left colon (8.7%), splenic angle (8.7%) and transverse colon (1.1%); being the size of the self-expandable metallic prostheses used 60x25 mm, 90x25 mm and 120x25 mm. The procedure was technically effective in 92.4% of the cases and clinically effective in 89.1%, with post-procedural perforations being detected in 9 patients (9.8%). Survival 30 days after prosthesis placement was 91.3%. No mortality directly related to the procedure was detected. In our experience, placement of self-expandable metallic prostheses is a safe and effective option in the initial management of neoplastic colon stenosis.

Experience in the treatment of esophageal anastomosis dehiscence using self-expanding metallic prosthesis.

INTRODUCTION: esophageal anastomosis dehiscence is a serious complication after esophageal cancer surgery with high mortality risk. One of the treatment options is self-expanding esophageal prostheses. Our aim was to evaluate the outcome of esophageal prostheses in the management of suture dehiscences after oncologic surgery. MATERIAL AND METHODS: we performed a descriptive and retrospective study with patients diagnosed with esophageal anastomosis fistula or dehiscence treated by esophageal prosthesis between the years 2015 and 2021. We considered technical success as the correct positioning of the prosthesis with visualization of anastomotic leak closure after release of the prosthesis during endoscopy, and clinical success the resolution of dehiscence after removal of the prosthesis 8 weeks after positioning. RESULTS: technical success was 95% and clinical success 89%. CONCLUSION: in our center, esophageal prostheses are a treatment option for fistulas and anastomotic dehiscence after surgery with a high success rate and few complications.

Experience with ustekinumab in reservoir Crohn's disease.

Crohn's disease of the reservoir is a pathology of difficult diagnosis and complex approach due to the scarce documented evidence on it. Recently, studies have been published on the treatment strategies available for this entity. Based on the above, we have analyzed the experience of our center in the treatment of reservoir Crohn's disease with one of the new biologic agents, ustekinumab.

Lymphocyte Profile and Immune Checkpoint Expression in Drug-Induced Liver Injury: An Immunophenotyping Study.

The identification of specific HLA risk alleles in drug-induced liver injury (DILI) points toward an important role of the adaptive immune system in DILI development. In this study, we aimed to corroborate the role of an adaptive immune response in DILI through immunophenotyping of leukocyte populations and immune checkpoint expressions. Blood samples were collected from adjudicated DILI (n = 12), acute viral hepatitis (VH; n = 13), acute autoimmune hepatitis (AIH; n = 9), and acute liver injury of unknown etiology (n = 15) at day 1 (recognition), day 7, and day >30. Blood samples from patients with nonalcoholic fatty liver disease (NAFLD; n = 20) and healthy liver controls (HLCs; n = 54) were extracted at one time point. Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA-4 that was determined intracellularly, using flow cytometry. At recognition, DILI demonstrated significantly higher levels of activated helper T-cell (P < 0.0001), activated cytotoxic T-cells (P = 0.0003), Th1 (P = 0.0358), intracellular CTLA-4 level in helper T-cells (P = 0.0192), and PD-L1 presenting monocytes (P = 0.0452) than HLC. These levels approached those of HLC over time. No significant differences were found between DILI and VH. However, DILI presented higher level of activated helper T-cells and CTLA-4 than NAFLD and lower PD-L1 level than AIH. Our findings suggest that an adaptive immune response is involved in DILI in which activated CD4+ and CD8+ play an important role. Increased expression of negative immune checkpoints is likely the effect of peripheral tolerance regulation.

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry.

BACKGROUND & AIMS: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. METHODS: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. RESULTS: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). CONCLUSIONS: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. LAY SUMMARY: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.

Incidence and prevalence of acute hepatitis E virus infection in patients with suspected Drug-Induced Liver Injury in the Spanish DILI Registry.

BACKGROUND AND AIMS: Drug-induced liver injury (DILI) presents with a wide phenotypic spectrum requiring an extensive differential diagnosis. Hepatitis E virus (HEV) is not systematically ruled out during acute hepatitis assessment in Spain. The aims of this study were to establish the role of HEV infection and its phenotypic presentation in patients initially suspected of DILI and to determine the anti-HEV seroprevalence rate. METHODS: An analysis of 265 patients with suspected DILI and considered for enrolment in the Spanish DILI Registry and 108 controls with normal liver profiles was undertaken. Anti-HEV Immunoglobulin (Ig) G antibodies were analysed in serum from all subjects. In those with serum samples extracted within 6 months from liver damage onset (n = 144), HEV antigen (Ag) and anti-HEV IgM antibodies were tested in duplicate by ELISA. In addition, RT-PCR was performed externally in eight patients. RESULTS: Out of 144 patients, 12 (8%) were positive for anti-HEV IgM, mean age was 61 years. Underlying hepatic diseases (OR = 23.4, P < .001) and AST peak >20 fold upper limit of normal (OR = 10.9, P = .002) were associated with the diagnosis of acute hepatitis E. The overall anti-HEV IgG seroprevalence rate was 35%, evenly distributed between patients with suspected DILI (34%), and controls (39%). CONCLUSIONS: HEV seroprevalence and acute hepatitis E rates are relatively high in Spain. A search for active HEV infection is therefore advised in patients assessed for suspicion of DILI, particularly in patients with underlying liver diseases and high transaminase levels.

Present and future management of viral hepatitis.

Viral hepatitis can result in important morbidity and mortality, with its impact on health conditioned by the specific type of hepatitis, the geographical region of presentation and the development and access to new drugs, among other factors. Most acute presentation forms are self-limiting and may even go unnoticed, with just a small percentage of cases leading to acute liver failure that may necessitate transplantation or even cause the death of the patient. However, when they become chronic, as in the case of hepatitis B virus and C virus, unless they are diagnosed and treated adequately they may have severe consequences, like cirrhosis or hepatocarcinoma. Understanding of the mechanisms of transmission, the pathogenesis, the presence of vaccinations and the development over recent years of new highly-efficient, potent drugs have meant that we are now faced with a new scenario in the management of viral hepatitis, particularly hepatitis B virus and hepatitis C virus. The spectacular advances in hepatitis C virus treatment have led the World Health Organization to propose the objective of its eradication by 2030. The key aspect to achieving this goal is to ensure that these treatments reach all the more vulnerable population groups, in whom the different types of viral hepatitis have a high prevalence and constitute a niche that may perpetuate infection and hinder its eradication. Accordingly, micro-elimination programs assume special relevance at the present time.

Clinical Characteristics and Outcome of Drug-Induced Liver Injury in the Older Patients: From the Young-Old to the Oldest-Old.

Older patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥ 65 years) were categorized according to age: "young" (< 65 years); "young-old" (65-74 years); "middle-old" (75-84 years); and "oldest-old" (≥ 85 years). All elderly groups had an increasingly higher comorbidity burden (P < 0.001) and polypharmacy (P < 0.001). There was a relationship between jaundice and hospitalization (P < 0.001), and both were more prevalent in the older age groups, especially in the oldest-old (88% and 69%, respectively), and the DILI episode was more severe (P = 0.029). The proportion of females decreased across age groups from the young to the middle-old, yet in the oldest-old there was a distinct female predominance. Pattern of liver injury shifted towards cholestatic with increasing age among top culprit drugs amoxicillin-clavulanate, atorvastatin, levofloxacin, ibuprofen, and ticlopidine. The best cutoff point for increased odds of cholestatic DILI was 65 years. Older patients had increased non-liver-related mortality (P = 0.030) as shown by the predictive capacity of the Model for End-Stage Liver Disease score (odds ratio (OR) = 1.116; P < 0.001), and comorbidity burden (OR = 4.188; P = 0.001) in the 6-month mortality. Older patients with DILI exhibited an increasingly predominant cholestatic phenotype across a range of culprit drugs, other than amoxicillin-clavulanate, with increased non-liver-related mortality and require a different approach to predict outcome. The oldest DILI patients exhibited a particular phenotype with more severe DILI episodes and need to be considered when stratifying older DILI populations.

Application of artificial intelligence in the diagnosis and treatment of hepatocellular carcinoma: A review.

Although artificial intelligence (AI) was initially developed many years ago, it has experienced spectacular advances over the last 10 years for application in the field of medicine, and is now used for diagnostic, therapeutic and prognostic purposes in almost all fields. Its application in the area of hepatology is especially relevant for the study of hepatocellular carcinoma (HCC), as this is a very common tumor, with particular radiological characteristics that allow its diagnosis without the need for a histological study. However, the interpretation and analysis of the resulting images is not always easy, in addition to which the images vary during the course of the disease, and prognosis and treatment response can be conditioned by multiple factors. The vast amount of data available lend themselves to study and analysis by AI in its various branches, such as deep-learning (DL) and machine learning (ML), which play a fundamental role in decision-making as well as overcoming the constraints involved in human evaluation. ML is a form of AI based on automated learning from a set of previously provided data and training in algorithms to organize and recognize patterns. DL is a more extensive form of learning that attempts to simulate the working of the human brain, using a lot more data and more complex algorithms. This review specifies the type of AI used by the various authors. However, well-designed prospective studies are needed in order to avoid as far as possible any bias that may later affect the interpretability of the images and thereby limit the acceptance and application of these models in clinical practice. In addition, professionals now need to understand the true usefulness of these techniques, as well as their associated strengths and limitations.

Drug-Induced Liver Injury After Liver Transplantation.

Drug-induced liver injury (DILI) is an adverse reaction to many drugs in common use that in a liver transplantation (LT) recipient may cause graft dysfunction and may even lead to graft loss and the need for retransplantation. However, several potential clinical scenarios, such as graft rejection and infection, can confound the diagnosis of suspected DILI in the setting of LT. This makes causal assessment of a new liver injury more uncertain and has traditionally precluded collection of bona fide cases of DILI affecting LT patients in prospective DILI registries and cohorts. Although no studies have yet determined a greater susceptibility of the transplant patient to DILI, these patients nevertheless present certain risk factors that can theoretically increase the risk of DILI. These include the fact that these patients are polymedicated, use drugs that are potentially hepatotoxic, and can have coexisting hepatitis B or C viruses in addition to other factors found in nontransplant patients, such as genetic variants. Therefore, awareness is crucial of any potential hepatotoxic effect of drugs used in the LT recipient and their possible implication in any case of liver dysfunction. In the present article, we review the most common drugs used in LT recipients from a liver safety perspective and address the main pitfalls in attributing causality in this clinical setting. We also affirm the need for further research and collaboration in this somewhat neglected topic in the field of DILI.

Exposición solar en la enfermedad inflamatoria intestinal ambulatoria: factores predictivos y correlación con la concentración sérica de vitamina D / Sunlight exposure in inflammatory bowel disease outpatients: Predictive factors and correlation with serum vitamin D

Introducción: La exposición solar es el principal determinante del estado de vitaminaD. Nuestro objetivo fue describir las prácticas de exposición y protección solar de una serie de pacientes con enfermedad inflamatoria intestinal (EII) y evaluar su influencia en la concentración sérica de vitaminaD. Pacientes y métodos: Estudio observacional de tipo transversal. Las variables clínico-demográficas se obtuvieron mediante entrevista clínica y revisión de la historia. La evaluación de la exposición solar se realizó mediante el Sun Exposure Questionnaire. La concentración de 25-hidroxivitaminaD (25OHD) se determinó por electroquimioluminiscencia. Se realizaron cuestionarios de calidad de vida, actividad física, ingesta semanal de vitaminaD y hábitos de protección solar. Resultados: Se incluyeron 149 pacientes. En el 69% de los pacientes se registraron valores deficientes o insuficientes de 25OHD. El 67% presentaron una baja exposición solar. Se observó una modesta correlación significativa entre la puntuación total del cuestionario de exposición solar y la concentración de 25OHD en la serie completa (r=0,226; p=0,006) y en verano (r=0,274; p=0,01). La puntuación del cuestionario de protección solar no influyó en la concentración de 25OHD. En el análisis multivariado solo la presencia de actividad clínica se asoció a una exposición solar baja (OR=3,23). Discusión: La exposición solar de acuerdo con el cuestionario empleado fue baja, se asoció a la presencia de actividad clínica y se correlacionó débilmente con la concentración de 25OHD sérica. Se necesitan más estudios que exploren el uso de cuestionarios individuales de exposición solar y su correlación con la vitaminaD sérica en la EII

Introduction: Sunlight exposure is the main source of vitaminD. Our aim was to describe both sun exposure and sun protection behaviour in a series of patients with inflammatory bowel disease (IBD), and to study their potential association with vitaminD concentration. Patients and methods: A cross sectional, observational study. The clinical-demographic variables were obtained via clinical interviews and medical history review. The sunlight exposure assessment was carried out using the Sun Exposure Questionnaire and the concentration of 25-hydroxy vitaminD (25OHD) was measured by an electro-chemiluminescence immunoassay. Questionnaires were conducted on quality of life, physical activity, weekly vitaminD intake and sun protection behaviour. Results: 149 patients were included. In 69% of patients, deficient or insufficient 25OHD values were recorded. 67% showed low sun exposure. A modest significant correlation was observed between the total score of the solar exposure questionnaire and the 25OHD concentration in the complete series (r=0.226, P=.006) and in the summer (r=0.274, P=.01). The sun protection behaviour questionnaire score did not influence the 25OHD concentration. In the multivariate analysis, only the presence of clinical activity was associated with low sun exposure (OR=3.23). Discussion: Sun exposure according to the questionnaire used was low, was associated with the presence of clinical activity and was weakly correlated with serum 25OHD concentration. More studies are needed to explore the use of individual questionnaires for sun exposure and its relationship with vitaminD in patients with IBD