Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

Persistent hepatic encephalopathy secondary to portosystemic shunt occluded with Amplatzer device.

Hepatic encephalopathy is a frequent complication of cirrhosis, when this event becomes persistent, treatment compliance should be verified and any precipitating factor need to be identified. Also the presence of portosystemic shunts, which are a rare cause of decompensation or persistence hepatic encephalopathy need to be ruled out. In this paper we report the case of a 57 year old man with persistent hepatic encephalopathy secondary to the presence of a porto-onfalo-femoral shunt successfully closed with the placement of an Amplatzer device.

Humoral response to different SARS-CoV-2 vaccines in orthotopic liver transplant recipients.

BACKGROUND: The safety and efficacy data of the different types of available vaccines is still needed. The goal of the present analysis was to evaluate the humoral response to the COVID-19 vaccines in orthotopic liver transplant (OLT) recipients. METHODS: Participants were included from February to September 2021. No prioritized vaccination roll call applied for OLT patients. Controls were otherwise healthy people. Blood samples were drawn after 15 days of the complete vaccine doses. The samples were analyzed according to the manufacturer's instructions using the Liaison XL platform from DiaSorin (DiaSorin S.p.A., Italy), and SARS-COV-2 IgG II Quant (Abbott Diagnostics, IL, USA). RESULTS: A total of 187 participants (133 OLT, 54 controls, median age: 60 years, 58.8% women) were included for the analysis; 74.3% had at least one comorbidity. The serologic response in OLT patients was lower than in controls (median 549 AU/mL vs. 3450 AU/mL, respectively; p = 0.001). A positive humoral response was found in 133 OLT individuals: 89.2% with BNT162b2 (Pfizer-BioNTech), 60% ChAdOx1 nCOV-19 (Oxford-AstraZeneca), 76.9% with CoronaVac (Sinovac, Life Sciences, China), 55.6% Ad5-nCov (Cansino, Biologics), 68.2% Gam-COVID-Vac (Sputnik V) and 100% with mRNA-1273. In controls the serological response was 100%, except for Cansino (75%). In a multivariable model, personal history of COVID-19 and BNT162b2 inoculation were associated with the serologic response, while the use of prednisone (vs. other immunosuppressants) reduced this response. CONCLUSION: The serologic response to COVID-19 vaccines in OLT patients is lower than in healthy controls. The BNT162b2 vaccine was associated with a higher serologic response.

Hepatic transplant during SARS-CoV-2 (COVID-19) pandemic. A literature review.

ANTECEDENTES: En diciembre de 2019 se identificó en la ciudad de Wuhan, China, un nuevo beta coronavirus, el SARS-CoV-2, como agente causal de neumonía grave, conocida como COVID-19, lo cual ha provocado medidas estrictas de aislamiento, cierre de programas de trasplante hepático y la necesidad de modificar los protocolos de tratamiento. OBJETIVO: Documentar la información publicada sobre el impacto de la COVID-19 en la población con antecedente de trasplante hepático y establecer un protocolo de tratamiento. MÉTODO: Se buscaron en PubMed los términos MeSH "SARS-CoV-2", "COVID-19", "trasplante hepático" y "tratamiento". RESULTADOS: Hasta el momento se ha demostrado en la población con trasplante hepático una mayor facilidad para adquirir el virus, sin una diferencia en la mortalidad al compararla con la población general. La inmunosupresión debe continuar, sin suspender los inhibidores de la calcineurina. Del tratamiento específico, los esteroides son los que han demostrado el mayor beneficio clínico y una disminución de la mortalidad. CONCLUSIÓN: El trasplante hepático no se asocia de manera independiente a una mayor mortalidad. Otros factores, además del trasplante, deben tomarse en cuenta al momento de establecer la gravedad. BACKGROUND: In December 2019, a new beta coronavirus, SARS-CoV-2, was identified in the city of Wuhan, China, as a causative agent of severe pneumonia, known as COVID-19, which has led to strict isolation measures, closure of liver transplantation programs and the need to modify treatment protocols. OBJECTIVE: Document the information published so far on the impact of COVID-19 in the population with a history of liver transplantation and establish a treatment protocol. METHOD: MeSH terms were searched for "SARS-CoV-2", "COVID-19", "liver transplantation" and "treatment". RESULTS: Up to now, a greater ease in acquiring the virus has been shown in the liver transplant population, without a difference in mortality when compared to the general population. Immunosuppression should continue at the minimum tolerated levels, without suspending calcineurin inhibitors. Of the specific treatment, steroids are those that have shown the greatest clinical benefit and decreased mortality. CONCLUSION: Liver transplantation is not independently associated with higher mortality. Factors other than transplantation must be taken into account when considering the risk of severity.

Direct-Acting Antivirals in the Treatment of Hepatitis C Virus Recurrence after Liver Transplantation: Real-life Experience in a Mexican Cohort.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the most frequent causes of liver transplantation (LT) worldwide. Patients with HCV viremia at the time of LT universally develop recurrent HCV in the allograft, leading to accelerated fibrosis and graft loss. Treatment with direct-acting antivirals (DAA) is highly effective and safe in this population. AIM OF THE STUDY: To describe the efficacy and safety of DAA in treating post LT HCV recurrence in a Mexican cohort. METHODS: We designed a retrospective cohort study that included all LT patients from 2000-2019 with HCV recurrence after LT who received DAA. Clinical and biochemical characteristics were collected from clinical records. Patients who received treatment before LT and those who received interferon-based therapies after LT achieving sustained viral response at 12 weeks were excluded; patients who didn´t complete DAA therapy were eliminated. The primary outcome was SVR-12. RESULTS: Fifty-six patients received DAA after the LT with 98% SVR-12. The most frequent genotypes were 1b (54%) and 1a (34%). The most common antiviral scheme used was sofosbuvir/ledipasvir for 12 weeks in 59% of the patients. No severe adverse effects were observed. Ribavirin was used in 82% of the patients, of which 23.9% had adverse effects, mostly mild. The median follow-up after LT was 55 months (IQR 43-51), with a global and graft survival at one and three years of 100%. CONCLUSION: In a Mexican cohort, DAA therapy in LT patients with recurrence of HCV infection showed high efficacy and an acceptable safety profile.

Prevalence and clinical characteristics of alpha-1 antitrypsin deficiency in liver explants in a Mexican cohort.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a risk factor for liver disease. PASD-positive inclusions have been found unexpectedly in approximately 10% of liver explants in patients with no previous diagnosis of AATD, particularly, in patients with non-alcoholic steatohepatitis (NASH), supporting a synergistic mechanism of liver injury between AATD and environmental factors. We aimed to determine the clinical characteristics of mestizo patients in which AATD was diagnosed before or after liver transplantation. METHODS: Liver explants of patients with cryptogenic, alcoholic, and NAFLD/NASH cirrhosis undergoing orthotopic liver transplantation (OLT) were included. Liver histopathology was assessed by two expert pathologists. Hematoxylin and eosin staining, PASD staining, and confirmatory AAT immunohistochemistry were performed. In explants with positive histopathology, genotyping for SERPINA1 was performed. RESULTS: A total of 180 liver transplants were performed during the study period. Of these, 44 patients with cryptogenic cirrhosis, NASH, and alcoholic cirrhosis were included. Of these patients, two liver explants (4.5%) had PASD-positive inclusions stain and confirmatory immunochemistry. During the period evaluated, another two patients with a diagnosis of AATD before the OLT were also included. The four patients had overweight or obesity, three had type 2 diabetes mellitus, and two developed liver steatosis after the OLT. CONCLUSION: AATD was found to be an infrequent finding in patients with cryptogenic, NASH/NAFLD, and alcoholic cirrhosis in our population. However, it is important to consider this entity as it may represent an additional factor in the appearance and progression of liver fibrosis in patients with metabolic syndrome.

Obesity in the Liver Transplant Setting.

The obesity epidemic has resulted in an increased prevalence of obesity in liver transplant (LT) candidates and in non-alcoholic fatty liver disease (NAFLD) becoming the fastest growing indication for LT. LT teams will be dealing with obesity in the coming years, and it is necessary for them to recognize some key aspects surrounding the LT in obese patients. Obesity by itself should not be considered a contraindication for LT, but it should make LT teams pay special attention to cardiovascular risk assessment, in order to properly select candidates for LT. Obese patients may be at increased risk of perioperative respiratory and infectious complications, and it is necessary to establish preventive strategies. Data on patient and graft survival after LT are controversial and scarce, especially for long-term outcomes, but morbid obesity may adversely affect these outcomes, particularly in NAFLD. The backbone of obesity treatment should be diet and exercise, whilst being careful not to precipitate or worsen frailty and sarcopenia. Bariatric surgery is an alternative for treatment of obesity, and the ideal timing regarding LT is still unknown. Sleeve gastrectomy is probably the procedure that has the best evidence in LT because it offers a good balance between safety and efficacy.