Extensive splanchnic vein thrombosis after SARS-CoV-2 vaccination: A Vascular Liver Disease Group (VALDIG) initiative.

BACKGROUND AND AIMS: Since the introduction of SARS-CoV-2 vaccines, several cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) have been described, especially cerebral vein thrombosis. We aimed to retrospectively collect all new cases of acute onset first or recurrent splanchnic vein thrombosis (SVT) following a recent SARS-CoV-2 vaccination within the Vascular Liver Disease Group network. APPROACH AND RESULTS: New cases of SVT were identified from April 2021 to April 2022; follow-up was completed on December 31, 2022. Criteria to define VITT were derived from previous studies. Data from a pre-COVID cohort of patients with SVT (N=436) were used for comparison of clinical presentation, etiology, and outcome. Twenty-nine patients were identified with SVT occurring with a median of 11 days (range 2-76) after the first (48%), second (41%), or third (10%) vaccination (ChAdOx1 nCov-19 (n=12) or BNT162b2 (n=14), other (n=3) Only 2 patients(7%) fulfilled criteria for definite VITT. Twenty (69%) had SVT at multiple sites, including 4 (14%) with concomitant extra-abdominal thrombosis. Only 28% had an underlying prothrombotic condition, compared to 52% in the pre-COVID SVT cohort ( p =0.01). Five patients (17%) underwent bowel resection for mesenteric ischemia, compared with 3% in pre-COVID SVT ( p <0.001). Two patients died shortly after diagnosis (7%). CONCLUSIONS: Although definite VITT was rare, in 72% of cases, no other cause for SVT could be identified following SARS-CoV-2 vaccination. These cases were different from patients with nonvaccine-related SVT, with lower incidence of prothrombotic conditions, higher rates of bowel ischemia, and poorer outcome. Although SVT after SARS-CoV-2 vaccination is rare in absolute terms, these data remain relevant considering ongoing revaccination programs.

Correlation between neuroimaging, neurological phenotype, and functional outcomes in Wilson's disease.

INTRODUCTION: Wilson's disease (WD) is associated with a variety of movement disorders and progressive neurological dysfunction. The aim of this study was to correlate baseline brain magnetic resonance imaging (MRI) features with clinical phenotype and long-term outcomes in chronically treated WD patients. METHODS: Patients were retrospectively selected from an institutional database. Two experienced neuroradiologists reviewed baseline brain MRI. Functional assessment was performed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale, and disease severity was classified using the Global Assessment Scale for Wilson's Disease (GASWD). RESULTS: Of 27 patients selected, 14 were female (51.9%), with a mean (standard deviation [SD]) age at onset of 19.5 (7.1) years. Neurological symptoms developed in 22 patients (81.5%), with hyperkinetic symptoms being the most common (70.4%). Baseline brain MRI showed abnormal findings in 18 cases (66.7%), including T2 hyperintensities in 59.3% and atrophy in 29.6%. After a mean (SD) follow-up of 20.9 (11.0) years, WD patients had a mean score of 19.2 (10.2) on WHODAS 2.0 and 6.4 (5.7) on GASWD. The presence of hyperkinetic symptoms correlated with putaminal T2 hyperintensities (p = 0.003), putaminal T2 hypointensities (p = 0.009), and mesencephalic T2 hyperintensities (p = 0.009). Increased functional disability was associated with brain atrophy (p = 0.007), diffusion abnormalities (p = 0.013), and burden of T2 hyperintensities (p = 0.002). A stepwise regression model identified atrophy as a predictor of increased WHODAS 2.0 (p = 0.023) and GASWD (p = 0.007) scores. CONCLUSIONS: Atrophy and, to a lesser extent, deep T2 hyperintensity are associated with functional disability and disease severity in long-term follow-up of WD patients.

Use of albumin infusion for cirrhosis-related complications: An international position statement.

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.

Correlation between individual autoantibodies and clinical features in primary biliary cholangitis: results of a retrospective longitudinal study.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an immune-mediated liver disease. The immunological profile seems to relate to clinical prognosis. This study aims to determine the role of autoantibodies in the course of liver disease and in the response to ursodeoxycholic acid. METHODS: Between January 2016 and December 2020, 143 patients with PBC who underwent immunological liver profile evaluation were enrolled. All data were extracted retrospectively from electronic clinical records. Chi-square test, Fisher's exact test and Mann-Whitney test were used to evaluate the relationship between autoantibodies and biochemical parameters, clinical outcomes and therapeutic response scores. A significance level of 0.05 was used. RESULTS: Antimitochondrial antibodies were present in 91.6%, antiglycoprotein-210 antibody (anti-gp210) in 18.2% and anti-Sp100 in 19.6% of patients. The incidence of liver-related death was higher in patients with autoimmune hepatitis variants. The occurrence of cirrhosis or portal hypertension was not linked to the presence of any of the autoantibodies tested. No relationship was found with the probability of dying or being transplanted. Patients with anti-Sp100 antibodies had higher baseline levels of aspartate aminotransferase and alanine aminotransferase and lower immunoglobulin M levels. Patients with anti-gp210 were more likely to have a lower median transplant-free survival rate and higher median risk of liver transplant or liver-related death using the GLOBE and UK-PBC scores. CONCLUSION: Our findings confirm a strong association between anti-gp210 antibodies and a worse outcome. The association between anti-Sp100 and hepatic lesions requires further elucidation.

Human Albumin Infusion for the Management of Liver Cirrhosis and Its Complications: An Overview of Major Findings from Meta-analyses.

INTRODUCTION: The role of human albumin (HA) infusion in cirrhotic patients has been increasingly recognized. This paper aims to summarize the evidence from meta-analyses regarding HA infusion for the management of cirrhosis and its complications. METHODS: A systematic search in the PubMed, EMBASE, and Cochrane library databases, and in reference lists was conducted. All relevant meta-analyses were identified and their findings were reviewed. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist was used to evaluate the methodological quality and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to assess the quality of evidence for significant outcomes. RESULTS: Among 300 papers initially identified, 18 meta-analyses have been included. Short- and long-term HA infusion at high doses decreased the mortality of patients with decompensated cirrhosis. In cirrhotic patients with ascites, long-term HA infusion reduced the recurrence of ascites, but not mortality. In cirrhotic patients undergoing large-volume paracentesis (LVP), HA infusion reduced the incidence of post-paracentesis circulatory dysfunction and hyponatremia, but not mortality or renal impairment. In cirrhotic patients with overt hepatic encephalopathy (HE), HA infusion improved the severity of overt HE, but not overall mortality. In cirrhotic patients with spontaneous bacterial peritonitis (SBP), but not those with non-SBP infections, HA infusion reduced the mortality and renal impairment. In cirrhotic patients with type-1 hepatorenal syndrome (HRS), an increment of 100 g in cumulative HA dose increased 1.15-fold survival, but not HRS reversal. In these meta-analyses, the quality of methodology was low or critically low, and that of the evidence was from very low to moderate. CONCLUSIONS: Based on the limited evidence from these meta-analyses, HA infusion appears to be beneficial in cirrhotic patients with ascites, overt HE, and SBP and in those undergoing LVP, but not in those with non-SBP infections.

Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Long-term Outcome.

BACKGROUND: Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. METHODS: Retrospective multicentre study of 79 patients who received LT for PSVD. RESULTS: Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. CONCLUSIONS: LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.

Dorfman-Chanarin Syndrome: A Rare Cause of Metabolic Associated Fatty Liver Disease Related to Homozygosity of the Nonsense Mutation c.934C>T (p.R312*).

Metabolic associated fatty liver disease became the most common form of chronic liver disease, in the vast majority of the cases related to increased insulin resistance or metabolic dysregulation. Yet, other causes may be implied. We report the late diagnosis of Dorfman-Chanarin syndrome in a non-alcoholic steatohepatitis previously labeled cirrhotic middle-aged man, with consanguineous parents, complicated with hepatocellular carcinoma. Congenital ichthyosis, neurosensory hearing loss and elevated muscular enzymes hit on the track of Dorfman-Chanarin syndrome. The genetic analysis uncovered a first-time described homozygotic nonsense mutation in the ABHD5 gene, responsible for coding the ABHD5 protein. The patient was successfully submitted to liver transplantation. Inborn errors of metabolism are a rare cause of metabolic associated fatty liver disease, but they need to be kept in consideration in all patients who present with atypical clinical features. This shall raise the awareness of physicians to rare forms of presentation since it may imply not only a different prognosis, but also other actions, like particular therapies as liver transplantation due to related complications of cirrhosis, or familial screening.

A doença hepática gorda dismetabólica tornou-se a forma mais comum de doença hepática crónica, estando mais vezes relacionada com o aumento da insulinorresistência ou desregulação metabólica. Contudo, outras causas podem estar também implicadas. Apresentamos o caso clínico de um doente com um diagnóstico de síndrome de Dorfman-Chanarin estabelecido tardiamente num homem de meia-idade com um diagnóstico prévio de cirrose associada a esteatohepatite não alcoólica, com pais consanguíneos, e complicada de carcinoma hepatocelular. A presença de ictiose congénita, a perda de audição neurosensorial, e a elevação de enzimas musculares, colocaram na pista de diagnóstico de síndrome de Dorfman-Chanarin. O estudo genético demonstrou a presença de uma mutação nonsense descrita pela primeira vez em homozigotia no gene ABHD5, responsável pela codificação da proteína ABHD5. O doente foi submetido a transplante hepático com sucesso. Os erros inatos do metabolismo são uma causa rara de doença hepática gorda, mas necessitam de ser tidos em consideração em todos os doentes que se apresentem com características clínicas atípicas. Isto deve aumentar a consciencialização dos médicos para formas raras de apresentação, uma vez que pode implicar não apenas um prognóstico diferente, mas também outras ações, como o transplante hepático por complicações associadas à cirrose, ou despiste familiar.

Epidemiology of portal vein thrombosis in liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis are heterogeneous among studies and have not been sufficiently determined yet. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched. Eligible studies would explore the prevalence and/or incidence of PVT in liver cirrhosis without hepatocellular carcinoma or abdominal surgery. Pooled proportion with 95% confidence interval (CI) was calculated using a random-effect model. Factors associated with the presence/occurrence of PVT were also extracted. RESULTS: Among the 8549 papers initially identified, 74 were included. Fifty-four studies explored the prevalence of PVT in liver cirrhosis with a pooled prevalence of 13.92% (95%CI=11.18-16.91%). Based on cross-sectional data, Child-Pugh class B/C, higher D-dimer, ascites, and use of non-selective beta-blockers (NSBBs) were associated with the presence of PVT in liver cirrhosis. Twenty-three studies explored the incidence of PVT in liver cirrhosis with a pooled incidence of 10.42% (95%CI=8.16-12.92%). Based on cohort data, Child-Pugh class B/C, higher model of end-stage liver disease score, higher D-dimer, lower platelets count, decreased portal flow velocity, ascites, use of NSBBs, and moderate or high-risk esophageal varices could predict the occurrence of PVT in liver cirrhosis. CONCLUSION: Approximately one seventh of cirrhotic patients have PVT, and one tenth will develop PVT. Progression of liver cirrhosis and portal hypertension seems to be in parallel with the risk of PVT. Prospective studies with detailed information about classification and extension of PVT in liver cirrhosis are needed.

The Role of a Medical Intermediate Care Unit in the Management of Budd-Chiari Syndrome: Case Series.

Budd-Chiari syndrome (BCS) has a wide spectrum of presentations, from an asymptomatic status to acute liver failure (ALF). The therapeutic approach depends on disease severity and related etiology with patients with severe forms of presentation classically managed in intensive care units (ICUs). Here, we report a series of five BCS patients managed in a medical intermediate care unit (IntCU), with three of them presenting with acute liver injury. Progression to ALF was seen in three patients, two of whom died, with one being successfully submitted to liver transplantation. IntCUs allow a 24-h patient surveillance and a prompt management of BCS, with less economic impact when compared to ICUs. Mortality was related to the presence of associated comorbidities that limited therapeutic approach.

Systemic inflammation as a risk factor for portal vein thrombosis in cirrhosis: a prospective longitudinal study.

BACKGROUND AND AIMS: Various risk factors for portal vein thrombosis (PVT) development in patients with cirrhosis have been identified, but the role of systemic inflammatory reaction is unknown. The study aims to assess the association between markers of systemic inflammation and PVT in cirrhosis. METHODS: Between January 2014 and October 2015, 107 outpatients with cirrhosis and no PVT were recruited, and followed till February 2017. White blood cell count, serum concentrations of high-sensitive C-reactive protein, ferritin, tumor necrosis factor-alpha and interleukin-6 (IL-6) were evaluated at baseline and every 3 or 6 months till PVT diagnosis or end of follow-up. RESULTS: Median age, model for end-stage liver disease (MELD) score and follow-up period of the studied population was 55 years (IQR 46-62 years), 9.6 points (IQR 7.5-12 points) and 19 months (12-24 months), respectively. PVT developed in 10.3% of the patients. Lymphocyte count below 1.2 ´ 109/L [hazard ratio, 6.04; 95% confidence interval (CI), 1.29-28.2; P = 0.022], IL-6 above 5.5 pg/mL (hazard ratio, 5.64; 95% CI, 1.21-26.33; P = 0.028) and neutrophil-to-lymphocyte ratio (hazard ratio, 1.46; 95% CI, 1.04-2.04; P = 0.028) were associated with a higher risk of PVT development. IL-6 and lymphopenia remained associated with subsequent PVT development after adjustment for nonselective beta-blockers, spleen size, portosystemic collaterals, oesophageal varices (grade ≥2) and ascites, but also with alcohol as the cause for cirrhosis and MELD ≥13. CONCLUSION: In patients with cirrhosis, markers of systemic inflammation IL-6 and lymphopenia are predictive of PVT independently of markers of portal hypertension. These results draw our attention on a factor so far overlooked in the pathogenesis of PVT.

Budd-Chiari Syndrome and Acute Liver Failure: An Uncommon Presentation of Acute Myeloid Leukaemia.

Acute liver failure (ALF) is a rare entity, particularly in the context of Budd-Chiari syndrome (BCS). BCS is an uncommon disorder with multiple risk factors, most commonly myeloproliferative disorders. In BCS, active search and exclusion of underlying malignancy is mandatory, particularly in the context of ALF, as it may contraindicate liver transplantation (LT). We present the case of a healthy 29-year-old male, without known risk factors for liver disease, who presented to the emergency department with abdominal pain, ascites, and jaundice. BCS with consequent severe acute liver injury with rapid progression to ALF was diagnosed. The patient was listed for LT. The study of peripheral blood finally revealed myeloid blasts, and flow cytometry showed a population of blast cells with abnormal immunophenotypic profile (CD33+ and myeloperoxidase, MPO+). The bone marrow biopsy showed morphological and immunophenotypic aspects of acute myeloid leukaemia (AML) FAB M1. This diagnosis was considered a formal contraindication to LT, so the patient was delisted. ALF contraindicated rescue chemotherapy and AML contraindicated LT. The patient died 48 h after ICU admission. The search for underlying neoplasia is mandatory in the context of BCS, moreover with associated ALF, as it may limit lifesaving treatments and interventions to supportive and palliative care.

A falência hepática aguda (FHA) é uma entidade rara, particularmente no contexto da Síndrome de Budd-Chiari (SBC). A SBC é uma doença incomum com múltiplos fatores de risco, principalmente as doenças mieloproliferativas. Na SBC, a procura ativa e exclusão de malignidade subjacente é obrigatória, particularmente no contexto de FHA, já que pode contraindicar o transplante hepático (TH). Apresentamos o caso de um homem de 29 anos saudável, sem fatores de risco conhecidos para doença hepática que se apresentou no serviço de urgência com dor abdominal, ascite e icterícia. A SBC associada a lesão hepática severa com rápida progressão para FHA foi diagnosticada e o doente colocado em lista para TH. O estudo do sangue periférico finalmente revelou a presença de blastos mieloides e a citometria de fluxo a presença de uma população de blastos com perfil imunofenotípico anormal (CD33 + e mieloperoxidase (MPO) +). A biópsia da medula óssea mostrou aspetos morfológicos e imunofenotípicos de leucemia mieloide aguda (LMA) FAB M1. Este diagnóstico foi considerado uma contraindicação formal para o TH, pelo que o doente foi retirado de lista. Pela FHA a quimioterapia de resgate estava também contraindicada. O doente faleceu 48 horas após a admissão na UCI. O despiste de neoplasia subjacente é obrigatório no contexto de SBC, ainda mais com FHA, pois pode limitar o tratamento lifesaving a cuidados de suporte e paliativos.

Improvement of Central Nervous System Vasculitis in a Patient with Chronic Hepatitis C Virus Infection after Treatment with an Interferon-Free Regimen.

BACKGROUND: Neurosarcoidosis is a rare manifestation of hepatitis C virus (HCV) infection, mainly in patients exposed to interferon-based therapies. Although we are living in a new era of HCV treatment, there is still little data concerning the treatment of extrahepatic complications of the disease with direct antiviral agents, especially rare ones such as neurosarcoidosis. SUMMARY: We present a rare case of central nervous system vasculitic lesions in the context of chronic HCV infection associated with mixed cryoglobulinemia, elevated angiotensin-converting enzyme (ACE) levels, and documentation of viral RNA in the cerebrospinal fluid in a treatment-naïve chronic HCV patient. Successful treatment with an interferon-free regimen improved all clinical manifestations, reduced the levels of serum ACE, and reduced the cryoglobulin levels to undetectable. MESSAGES: Neurosarcoidosis and cryoglobulinemia are rare but well-recognized complications of HCV infection, even in treatment-naïve patients. Direct antiviral agents can be useful in the management of this condition.

INTRODUÇÃO: A neurossarcoidose é uma manifestação rara da infeção por hepatite C, sobretudo associada a exposição prévia a esquemas com interferão. Apesar de estarmosnuma nova era do tratamento da hepatite C, há ainda poucos dados em relação ao papel dos antivíricos de ação direta no tratamento das complicações extrahepáticas da doença, especialmente as raras, como a neurossarcoidose. SUMÁRIO: Apresentamos um caso raro de vasculite do Sistema nervoso central associada a elevação dos níveis de enzima conversora da angiotensina, documentação de RNA viral no líquido cefalo-raquidiano num doente com infeção crónica a hepatite C sem tratamentos prévios. O tratamento com antivíricos de ação direta melhorou todas as manifestações clínicas, incluindo redução dos níveis de ECA e de crioglobulinas. MENSAGENS: A neurossarcoidose é uma rara, mas bem reconhecida complicação da hepatite C, mesmo em doentes sem exposição prévia a interferão. Os agentes de ação direta podem ser úteis na gestão de ambas as doenças.

Porto-sinusoidal vascular disease: proposal and description of a novel entity.

Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.

Nonselective beta-blockers and the risk of portal vein thrombosis in patients with cirrhosis: results of a prospective longitudinal study.

BACKGROUND: Nonmalignant portal vein thrombosis is a significant event in the course of cirrhosis that can contraindicate liver transplantation and even impact survival after the surgical procedure. Risk factors are not completely known or validated and are still debated. AIM: To identify in patients with cirrhosis the risk factors for portal vein thrombosis that are assessable in clinical practice. METHODS: Between January 2014 and February 2017, 108 outpatients with cirrhosis and no portal vein thrombosis (78% Child A) were enrolled. Doppler ultrasound was performed every 3 or 6 months, for a median follow up of 19 months. RESULTS: Portal vein thrombosis developed in 11 patients. Nonselective beta-blockade (hazard ratio [HR] 10.56; 95% confidence interval [CI]: 1.35-82.73; P = 0.025), and medium or large-sized oesophageal varices (HR 5.67; 95% CI: 1.49-21.63; P = 0.011) at baseline were associated with portal vein thrombosis development. Although heart rate (P < 0.001) and portal blood flow velocity at baseline (P = 0.005) were significantly reduced by nonselective beta-blockers, they were not related to portal vein thrombosis development. CONCLUSIONS: Our findings confirm an association between portal vein thrombosis development and oesophageal varices at baseline, but suggest that the association could be explained by exposure to nonselective beta-blockers, independently from effects on heart rate and portal blood flow velocity. The mechanisms that explain portal vein thrombosis development in patients on nonselective beta-blockers require elucidation in order to optimise targeting of nonselective beta-blockade in patients with cirrhosis.

Acute hepatitis B virus infection and severe non-immune haemolytic anaemia: a rare relationship.

The clinical presentation of acute hepatitis B virus (HBV) infection is usually related to the onset of liver failure and damage. Anaemia may occur, but it is only rarely attributed to haemolysis. The authors report about the case of a 41-year-old woman with the diagnosis of acute HBV infection and coagulopathy (without encephalopathy) who developed non-immune haemolytic anaemia. Total recovery of the analytical liver profile, coagulopathy and anaemia was achieved through treatment targeting HBV.This case shows that, although rare, non-immune haemolytic anaemia may occur in association with acute HBV infection and that HBV suppression seems to lead to progressive anaemia resolution.

Efficacy and Safety of Direct-Acting Oral Anticoagulants Use in Acute Portal Vein Thrombosis Unrelated to Cirrhosis.

In acute portal vein thrombosis (APVT) unrelated to cirrhosis, anticoagulant therapy is classically started with low molecular weight heparin or vitamin K antagonists. New direct-acting oral anticoagulants (DOACs) are used in the treatment of venous thrombosis outside the splanchnic vascular bed, but not in the latter. We report a young female with APVT occurring in a non-cirrhotic liver linked to heterozygosity of factor V-Leiden and prothrombin G20210A gene mutations. Rivaroxaban was started, with total recanalization of the left and partial recanalization of the right portal vein branches, without complications. New DOACs do not need daily subcutaneous injections nor routinely blood coagulation control tests, making its use attractive, eventually increasing patient's compliance. If proved to be safe and effective in the future studies, its use may be extended to PVT treatment. This case shows that rivaroxaban was safe, not only prevented the extension of thrombosis in the portal tract, but also resolved PVT, at least partially.