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Introduction: liver enzyme elevation has been reported in SARS-CoV-2 disease (COVID-19) in heterogeneous cohorts, mainly from China. Comprehensive reports from other countries are needed. In this study, we dissect the pattern, evolution, and predictive value of such abnormalities in a cohort from Madrid, Spain., Methods: a retrospective study with a prospective 14-day follow-up of 373 patients with confirmed COVID-19 in five Madrid hospitals, including 50 outpatients. A COVID-19 severe course was defined as the need for mechanical ventilation., Results: a total of 33.1 % of hospitalized patients showed baseline AST elevation and 28.5 % showed ALT elevation, compared with 12 % and 8 % of outpatients (p ≤ 0.001). Baseline AST, ALT and GGT levels correlated with LDH and C-reactive protein (CRP) levels (r ≤ 0.598, p < 0.005). AST elevation was associated with other severity markers such as male sex, lymphopenia, and pneumonia on X-Ray (p < 0.05 for all). ALP and bilirubin levels were rarely increased. Patients with elevated baseline AST showed a progressive normalization of this enzyme and an increase in ALT and GGT levels. Patients with normal baseline AST showed a flattened evolution pattern with levels within the range. Patients with a severe course of COVID-19 more frequently showed elevated baseline AST than those with a milder evolution (54.2 % vs. 25.4 %, p < 0.001). Age, AST and CRP were independent risk factors for a severe course of COVID-19., Conclusion: mild liver enzyme elevation is associated with COVID-19 severity. Baseline AST is an independent predictor of severe COVID-19 course, and tends to normalize over time. ALT and GGT show a late elevation.

The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM-1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT-/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV- patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Autoimmune hepatitis (AIH) is a chronic liver disease able to progress to acute liver failure, cirrhosis, and liver cancer. A significant proportion of patients fail to first-line therapy or develop severe toxicity., Aims: To assess safety and effectiveness of tacrolimus as a second-line therapy in AIH patients., Methods: Multicentric retrospective study of AIH patients treated with tacrolimus for at least 3 months as a second-line therapy. Effectiveness was defined as complete normalization of transaminases and IgG., Results: A total of 23 AIH patients were included in the final analysis. In 13% of patients tacrolimus was initiated because of toxicity to previous first-line treatments and the rest were switched because of previous non-efficacy. Tacrolimus was effective in 18 patients (78%; 95%CI: 55.20-91.92%). The median time receiving tacrolimus was 16 months (IQR 20). There was a sustained response with a significant improvement in all liver enzymes and IgG on last follow-up. Only one patient discontinued tacrolimus at the third month because of severe neuropathy, and ototoxicity. Responders were significantly older at diagnosis of AIH (41 ± 13 vs. 27 ± 10 years old; p = 0.0496)., Conclusion: Tacrolimus is effective and well tolerated as a second-line therapy in patients with AIH., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: the presence of donor-specific antibodies (DSA) is thought to affect survival of the allograft and patient after liver transplantation (LT). However, their significance is not well understood., Patients and Methods: a prospective study was performed of 32 adult patients who underwent LT in 2011 to analyze the existence of DSA, associated risk factors and medium-term impact. Immunological determinations were performed immediately before LT and at three, six, 12 months and five years after LT., Results: eight patients (24.2 %) presented pre-formed DSA. However, titers were negative in all patients five years after LT and there were no associated events. Eight out of 24 patients (33.3 %) developed de novo DSA. After five years, only two remained positive; both were class II with high mean fluorescence intensity (MFI) values at diagnosis (over 15,000). No association was found between the development of DSA and the risk of rejection, graft loss or death. However, an increase in liver stiffness values was observed in patients with persistent DSA, and focal sinusoidal deposition of C4d and moderate liver fibrosis were reported., Conclusion: the incidence of DSA is high after LT. In addition, the persistence of de novo DSA could be associated with silent liver fibrosis with a potential impact on graft outcomes.

Budd-Chiari syndrome (BCS) is characterized by an obstruction of hepatic venous outflow from small hepatic veins to inferior vena cava, caused by acute thrombosis or its fibrous sequellae. An underlying myeloproliferative neoplasm is present in 50% of cases. Clinical manifestations are widely variable, from asymptomatic to fulminant episodes. Long-term complications range from cirrhosis to hepatocellular carcinoma. Behçet's disease (BD) is a rare recurrent inflammatory multisystemic disorder characterized by recurrent skin-mucosa lesions and systemic involvement. Vascular involvement is observed in up to 40% of the patients with BD, and it is one of the major causes of mortality and morbidity. BCS is a rare complication of BD with a frequency of < 5% among patients with vascular involvement. Immunosuppressive treatment is the cornerstone for the management of vascular involvement in BD, while anticoagulant therapy has been an issue of debate. Transjugular intrahepatic portosystemic shunt (TIPS) in severe cases of BCS-of all causes- improves survival. However, there is scarce evidence about the role of TIPS in the setting of BCS in BD. We present a case of a vascular Behçet's disease associated with chronic Budd-Chiari syndrome with progression of thrombosis despite adequate anticoagulant and immunosuppressive treatment, successfully managed with TIPS.

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events ( i.e ., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE., Competing Interests: Conflict-of-interest statement: The authors do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Background: Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma., Methods: This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively., Results: Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cut-off for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%., Conclusions: Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.

Background and Aim: Assessment of the severity of liver disease following infection with hepatitis C virus (HCV) is important in treatment selection and prognosis. As invasive liver biopsy procedures are regarded as the reference method to assess the stage of fibrosis, it is important to identify patient characteristics that are predictive of liver fibrosis severity. The aim of the study was to describe the distribution of liver severity scores, clinical characteristics, and physicians' assessment of fibrosis among HCV patients in five European countries., Methods: This cross-sectional study retrospectively reviewed the medical records of patients who were chronically infected with HCV in 2006. Patients managed for HCV at any of 60 sites in France, Germany, Italy, Spain, and the UK were included. Data collected included patient demographics and clinical characteristics. A combination of univariate and multivariate regression analyses were used to identify predictors of fibrosis severity and factors associated with undergoing biopsy., Results: Four thousand five hundred and ninety-four chronically infected HCV patients were included in this analysis. Management approaches differed between countries, with variations in biopsy use (59.3-18.4%) and preferred fibrosis scoring systems. Where histology results were available, 43.4%, 23.8%, and 32.9% had mild, moderate, and severe fibrosis, respectively. Factors associated with undergoing a biopsy included male gender and co-infection with hepatitis B virus. Chronic alcoholism, a lower first platelet count, and older age were predictors of increased liver fibrosis severity., Conclusions: These data suggest that there are major differences in how specialists manage their HCV patients across five major European countries., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Objectives: To assess survival and predictive factors of mortality after an episode of spontaneous bacterial peritonitis (SBP) in cirrhotic patients and to analyze the diagnostic and therapeutic measures used., Methods: We retrospectively reviewed the medical records of 158 consecutive episodes of SBP treated between January 2003 and December 2005. Survival was studied by Kaplan-Meier curves, compared by the log-rank test. Independent predictive factors of mortality were obtained by a Cox regression model, while independent predictive factors of in-hospital mortality were obtained by logistic regression analysis., Results: A total of 80.4% of the SBP episodes occurred in men and the mean age was 61.23 +/- 12.49 years. The most frequent etiology of cirrhosis was viral (51.3%), followed by alcoholic (39.9%). The distribution of Child-Pugh classification was 5.7% (A), 63.3% (B) and 31% (C). Overall 3-year survival in the sample was 43.3%. Four variables were identified as independent predictive factors of in-hospital and 3-month mortality: renal impairment, hepatic encephalopathy, diagnosis of hepatocellular carcinoma (HCC) and mean arterial pressure (MAP) < 75 mmHg. At the end of the monitoring period, the results of the analysis were as follows: diagnosis of HCC, MAP < 75 mmHg, and age > 65 years. Microbiological detection was achieved in 21% of the episodes. The most frequent microorganisms detected were Escherichia coli in ascitic fluid and Staphylococcus aureus in blood cultures., Conclusions: SBP has a poor short- and long-term prognosis in cirrhotic patients. Independent predictive factors of short-term survival are renal impairment, hepatic encephalopathy, MAP < 75 mmHg, and the presence of HCC.

Objective: Analyze the frequencies of genetic mutation in alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450 2E1 (CYP2E1) and establish their possible association with the development of acute alcoholic hepatitis (AAH)., Methodology: Case-control study in a total of 85 Spanish patients. We distinguish three groups (one case group and two control groups) based on hepatic histological lesion and alcohol consumption: controls (group 1: teetotalers; group 2: drinkers without AAH; cases: group 3: drinkers with AAH). Case diagnosis was established based on the presence of polymorphonuclear leukocyte infiltrate in histological study. We analyzed the presence of the genetic mutations R47H and R369C (ADH2), E487K (ALDH2) and mutation Rsa I of CYP2E1 (allele c2) by polymerase chain reaction (PCR) and capillary electrophoresis., Results: The allele c2 of CYP2E1 was found in 10%, 16% and 50% of the groups 1, 2 and 3 patients, respectively. Presence of the mutation Rsa I showed influence on the development of AAH (odds ratio [OR]: 3.63; confidence interval (95% [CI]: 0.88-15.02)., Conclusions: The data suggest a possible association between the presence of the Rsa I of CYP2E1 and the development of AAH in patients with chronic alcohol consumption.

Mortality among patients with liver insufficiency continues to be unacceptably high. The prognosis of patients with acute episodes of chronic liver insufficiency is almost as poor as that of patients with acute liver failure. Therefore, systems that support liver function, either until liver transplantation can be performed or until resolution of the situation before acute injury occurs, are essential. Albumin dialysis is a system of artificial liver support that allows detoxification of albumin-related and hydrosoluble substances, thus maintaining the patient's homeostasis. Current clinical experience of this therapy is still limited, although beneficial effects on clinical, laboratory and hemodynamic parameters have been demonstrated. Multicenter, controlled trials to evaluate the effect of this therapy on survival in distinct diseases are needed.

Liver abscess is a rare complication of Crohn's disease. Its prevalence and mortality are higher in patients with Crohn's disease than in the general population. Owing to its nonspecific clinical presentation, which may be mistaken for reactivation of Crohn's disease or be masked by simultaneous steroid therapy, a high index of suspicion is required for an early diagnosis and prompt treatment. We report 3 cases of Crohn's disease complicated with liver abscess in which the only common features were the absence of clinical or even endoscopic activity of Crohn's disease at diagnosis and the presence of an anastomotic leak due to right ileocolectomy in the previous year. In all patients, outcome was satisfactory with antibiotic therapy and percutaneous catheter drainage.

Despite remarkable medical advances during the last few years, liver failure--both acute and chronic--still results in high mortality. Since liver transplant programs were developed to improve survival in numerous hepatic end-stage disorders, fewer than 15% of patients with liver failure do actually receive a transplantation, be it because of the presence of procedural contraindications (toxic habits, age, concurrent disease), or of clinical conditions that may render surgery more difficult or worsen transplant prognosis. All these circumstances encouraged the development of alternative procedures to increase liver graft availability, as is the case of liver partition techniques and living-donor transplantation. On the other hand, organ scarcity for transplantation during the 1960s encouraged the parallel development of liver support systems in an attempt to reduce mortality and to improve patient survival while waiting for a transplant. Such systems attempt to replace a number of synthesis and detoxification functions for the damaged liver parenchyma. During the past few years both bioartificial systems--also referred to as "bioartificial livers"--based on bioreactors containing functionally active living hepatocytes, and extracorporeal liver detoxification systems have been developed. The latter type includes the so-called MARS (molecular adsorbent recirculating system) system, which combines albumin-bound molecule clearance and novel dialysis membrane biocompatibility.

Splenic artery aneurysms (SAA) are not uncommon in patients with hepatic transplant (HT). Three in 150 transplanted patients in our institutions were diagnosed with SAA and two of them had a spontaneous rupture. In two patients embolization with interventionist radiology was performed with excellent results. SAA should be investigated before and after HT and be treated with embolization as soon as possible because of the high risk of rupture.

When the hepatic artery is not available in liver transplantation because of its bad quality or low flow, arterial grafts from the donor have to be used to obtain arterial blood flow from the aorta. The case of use of a vascular PTFE prosthesis when no vascular grafts were available is presented, with good outcome 6 months after transplantation.

We report a case of ischemic hepatitis following a percutaneous liver biopsy in a 51 year old female patient, who had had an orthotopic liver transplant 6 months before. The angiographic study demonstrated a marked stenosis in the hepatic artery at the anastomosis site and a small arterioportal fistula. We suggest that the percutaneous liver biopsy was partially responsible for the ischemic hepatitis, due to the development of a small arterioportal fistula in a previously damaged vascular area with hepatic artery stenosis.

Unlabelled: HBV hepatitis is a severe complication of orthotopic liver transplantation (OLT) due to the immunosuppression therapy., Objectives: The aim of this study is to evaluate the efficacy of the active HBV immunization on these patients before OLT., Patients and Methods: This was a prospective trial, with 34 patients (20 M and 14 F), that received a double dose (40 micrograms) of HBV surface proteic Ag, on the 0th, 30th and 60th days of the study and posterior control of anti-HBs levels. If there wasn't a response, they received two more doses on the 90th and 120th days., Results: There was a seroconversion in 22 patients (64.7%). Chronic alcoholism determined a lower rate of response than other etiologies (p < 0.05); this was the same in HCV chronic liver disease (p < 0.01). During their follow up, two patients had acute HBV hepatitis: one of them presented a negative response from the beginning, and in the other, anti-HBs developed transiently, when the HBV markers appeared., Conclusions: Previous HBV active immunization in OLT patients with double dose in a quick sequence, determined a positive response in a high number of patients with a higher rate of seroconversion than in other studies. The response was not so high in patients with chronic alcoholism or HVC chronic liver disease. We conclude that HVB vaccination should be done in these patients.

During a 3-year period between 1990 and 1993, 100 patients received orthotopic liver transplantation at the "Gregorio Marañón" University General Hospital. The mean age of the patients was relatively high (46.9 +/- 10 years), with an important number of cirrhotic patients (91%). The rate of primary liver failure was relatively low (4.5% of transplantations) although 12 cases with more than 55 years were included in the present series. Eleven retransplantations were performed, 8 for early failure of the graft and 3 for chronic failure. Postoperative complications of the graft were vascular in 9 cases, biliary in 17 cases, and acute rejection (cellular) in 70 patients, although only 50 of these patients required treatment with steroid boluses. Infections were diagnosed in 60 cases with 80% of major infections, 6 of them caused by Aspergillus fumigatus that were lethal in all the cases. Postoperative survival was 82%, 72%, 69% and 69% at 1 month, 6 months, 1 year and 2 years respectively.

We report six cases of essential mixed cryoglobulinemia associated with chronic liver disease and positive HCV markers, who showed several acute symptoms of vasculitis, arthralgias, neuropathy and glomerulonephritis. The presence in the serum and cryoprecipitates of anti HCV antibodies detected by the second-generation ELISA (ELISA 2) and the of HCV RNA by PCR in the serum in all six cases, suggest an important role for this virus in the pathogenesis of mixed cryoglobulinemia.

Recurrence of hepatocellular carcinoma is rarely treated by surgical resection and has not been reported in the main series of liver transplantation. In this paper we present the case of a patient transplanted for hepatocellular carcinoma on cirrhosis who developed a tumoral recurrence in the transplanted liver four months later. The new tumor was removed by hepatectomy and the patient is free of tumor 24 months after resection. Surgical resection should be considered a treatment of tumoral recurrence after liver transplantation as is done after hepatectomy.

Angiosarcoma of the liver is an extremely rare tumor with a rapidly fatal course. This report describes the case of a 52-year-old male with an hepatic angiosarcoma not related to any known carcinogen. The hepatosplenic metastases and the brief clinical course, did not let us to complete diagnostic and therapeutic strategies.

Epidemiological data from two series of patients in whom acute pancreatitis (AP) was diagnosed, with a chronological difference of four years between them, were compared. A total of 142 events of AP were analyzed from 128 clinical records. The mean age of incidence was significantly higher among the most recent series (61.04 +/- 17.83 years vs 51.66 +/- 14.06 years), and no differences were observed with regard to distribution by sex. The most frequent etiology in both series was biliary lithiasis, followed by ethylism, both of them clearly associated with female and male sex, respectively. In the AP of alcoholic etiology, the mean age at onset was smaller than in the other etiological groups and this observation was more evident in the second series. Finally, mortality was significantly reduced in the most recent series (12.3% for the first series vs 5.7% for the second series).

Under certain conditions a percutaneous liver biopsy cannot be carried out. In many of these patients transjugular liver biopsy is the correct option. We present our first hundred biopsies: in 92 cases a liver specimen was obtained; in 80 cases (87%) the tissue specimen allowed the histopathologic diagnosis; in five cases perforation of the hepatic capsule was observed, without producing hemoperitoneum. The mortality in our series was nil. In our experience and the revision of the literature, we consider that transvenous (transjugular) needle biopsy is an efficient and reliable procedure.

The case of a 57-year-old male diagnosed as having Budd-Chiari syndrome secondary to a polycythemia vera, which produced a thrombosis of the suprahepatic veins as a first manifestation, is presented. The rarity of this clinical case and the rapidly lethal evolution of the patient, confirms the bad prognosis of this association.

We present 13 patients with 15 episodes of colonic volvulus, who underwent colonoscopy to decompress and/or devolvulate. Colonoscopic exploration demonstrated a non obstructive dilatation in three cases. In the remaining 10 patients, with 12 episodes of volvulus, decompression was obtained in 83.3% and devoluvulation in 41.6%. There were two failures, due to peritoneal metastases and adhesions which fixed the volvulus. In 40% of the cases there were mild ischemic signs. Forty per cent of the patients were submitted to elective surgery and the two failures (20%) were operated in emergency. The remaining 4 patients declined surgical treatment. At is allows differential diagnosis, we think that, for these patients, colonoscopy should be the first therapeutic approach; it also allows decompression and/or devolvulation and an early diagnosis of the associated ischemia.

124 cases of chronic inflammatory bowel disease were retrospectively reviewed between 1983 and 1988 (44 affected by Crohn's disease (CD) and 80 by ulcerative colitis (UC)). A median annual incidence of 1.30/100,000 inhabitants/year for CD and 2.37 for UC was found, observing an increase in the incidence of CD and a stabilization of UC.

In a preliminary study of the immunological aspects of intestinal inflammatory disease we found an immunological deficit of T helper lymphocytes, decreased monocytes and chemotaxis and poor response to nonspecific mitogen stimulus. Based on these findings, the study was repeated in the same patients three years later to confirm the evolution of this deficit. Recuperation was observed in the cases in which the disease evolved favorably, suggesting that certain aspects of the immune disorder might be secondary.