Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here we investigate the prognostic value of HVPG in compensated (cACLD) MASLD. METHODS: This European multicentre study included MASLD-cACLD patients characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: 340 MASLD-cACLD patients [56.2% men; age: 62 (55-68) years; MELD: 8 (7-9); 71.2% diabetes] were included. Clinically significant portal hypertension (CSPH; i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio, SHR:5.13; p<0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (aSHR per mmHg:1.12; p<0.001). Liver-related mortality occurred in 37 patients with a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (aSHR per mmHg:1.20; p<0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. While MASLD-cACLD patients without CSPH show a very low short-term risk of decompensation and liver-related mortality is rare, the presence of CSPH substantially increases both risks. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in MASLD-cACLD patients without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk-stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors.

BACKGROUND & AIMS: There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. METHODS: Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. RESULTS: Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. CONCLUSIONS: MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.

Ectopic variceal bleeding secondary to porto-sinusoidal vascular disease.

Porto-sinusoidal vascular disease (PSVD) is an uncommon cause of portal hypertension (PHT) characterized by typical manifestations of PHT in the absence of an identifiable cause such as cirrhosis or splenoportal thrombosis (1). There are different etiological factors, including oxaliplatin (2). We present the case of a 67-year-old male with a history of locally advanced rectal cancer in 2007 treated with chemotherapy (capecitabine, folinic acid, 5-fluorouracil and oxaliplatin), radiotherapy and surgery with a definitive colostomy. He was admitted for lower gastrointestinal bleeding from the colostomy with no anemia or hemodynamic repercussion. Colonoscopy was performed and no lesions were found. Abdominal computed tomography (CT) showed peristomal varices with porto-systemic collaterals at that level. There was splenomegaly, no evidence of chronic liver disease and the splenoportal axis was permeable. Laboratory tests showed chronic thrombocytopenia. Laboratory results excluded other causes of liver disease, hepatic elastography showed a value of 7.2 kPa and upper gastrointestinal endoscopy ruled out esophagogastric varices. The catheterisation of hepatic veins demonstrated a hepatic venous pressure gradient of 13.5 mmHg and liver biopsy revealed sinusoidal dilatation with sinusoidal and perivenular fibrosis. Because of the clinical context of the patient with a history of treatment with oxaliplatin, he was diagnosed with peristomal ectopic varices secondary to porto-sinusoidal vascular disease. Due to bleeding recurrence, it was finally decided to place a transjugular intrahepatic portosystemic shunt (TIPS).

Non-invasive tests for clinically significant portal hypertension after HCV cure.

BACKGROUND & AIMS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10 mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting. METHODS: A total of 418 patients with pre-treatment HVPG ≥6 mmHg who achieved sustained virological response (SVR) and underwent post-treatment HVPG measurement were assessed, of whom 324 (HVPG/NIT-cohort) also had paired data on pre-/post-treatment LSM/PLT. The derived LSM/PLT criteria were then validated against the direct endpoint decompensation in 755 patients with compensated advanced chronic liver disease (cACLD) with SVR (cACLD-validation-cohort). RESULTS: HVPG/NIT-cohort: Among patients with cACLD, the pre-/post-treatment prevalence of CSPH was 80%/54%. The correlation between LSM/HVPG increased from pre- to post-treatment (r = 0.45 vs. 0.60), while that of PLT/HVPG remained unchanged. For given LSM/PLT values, HVPG tended to be lower post- vs. pre-treatment, indicating the need for dedicated algorithms. Combining post-treatment LSM/PLT yielded a high diagnostic accuracy for post-treatment CSPH in cACLD (AUC 0.884; 95% CI 0.843-0.926). Post-treatment LSM <12 kPa & PLT >150 G/L excluded CSPH (sensitivity: 99.2%), while LSM ≥25 kPa was highly specific for CSPH (93.6%). cACLD-validation-cohort: the 3-year decompensation risk was 0% in the 42.5% of patients who met the LSM <12 kPa & PLT >150 G/L criteria. In patients with post-treatment LSM ≥25 kPa (prevalence: 16.8%), the 3-year decompensation risk was 9.6%, while it was 1.3% in those meeting none of the above criteria (prevalence: 40.7%). CONCLUSIONS: NITs can estimate the probability of CSPH after HCV cure and predict clinical outcomes. Patients with cACLD but LSM <12 kPa & PLT>150 G/L may be discharged from portal hypertension surveillance if no co-factors are present, while patients with LSM ≥25 kPa require surveillance/treatment. LAY SUMMARY: Measurement of liver stiffness by a specific ultrasound device and platelet count (a simple blood test) are broadly used for the non-invasive diagnosis of increased blood pressure in the veins leading to the liver, which drives the development of complications in patients with advanced liver disease. The results of our pooled analysis refute previous concerns that these tests are less accurate after the cure of hepatitis C virus (HCV) infection. We have developed diagnostic criteria that facilitate personalized management after HCV cure and allow for a de-escalation of care in a high proportion of patients, thereby decreasing disease burden.

Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases.

BACKGROUND & AIMS: Vascular liver diseases (VLDs) are represented mainly by portosinusoidal vascular disease (PSVD), noncirrhotic splanchnic vein thrombosis (SVT), and Budd Chiari syndrome (BCS). It is unknown whether patients with VLDs constitute a high-risk population for complications and greater coronavirus disease 2019 (COVID-19)-related mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to assess the prevalence and severity of SARS-CoV-2 infection among patients with VLDs, as well as to assess its impact on hepatic decompensation and survival. METHODS: This is an observational international study analyzing the prevalence and severity of SARS-CoV-2 infection in VLDs between March 2020 and March 2021, compared with the general population (GP). Patients from Spain (5 centers; n = 493) and France (1 center; n = 475) were included. RESULTS: Nine hundred sixty-eight patients were included: 274 with PSVD, 539 with SVT, and 155 with BCS. Among them, 138 (14%) were infected with SARS-CoV-2: 53 with PSVD, 77 with SVT, and 8 with BCS. The prevalence of SARS-CoV-2 infection in patients with PSVD (19%) and SVT (14%) was significantly higher than in the GP (6.5%; P < .05), whereas it was very similar in patients with BCS (5%). In terms of infection severity, patients with VLDs also presented a higher need of hospital admission (14% vs 7.3%; P < .01), intensive care unit admission (2% vs 0.7%; P < .01), and mortality (4% vs 1.5%; P < .05) than the GP. Previous history of ascites (50% vs 8%; P < .05) and post-COVID-19 hepatic decompensation (50% vs 4%; P < .05) were associated with COVID-19 mortality. CONCLUSIONS: Patients with PSVD and SVT could be at higher risk of infection by SARS-CoV-2 and at higher risk of severe COVID-19 disease.

Decompensation in Advanced Nonalcoholic Fatty Liver Disease May Occur at Lower Hepatic Venous Pressure Gradient Levels Than in Patients With Viral Disease.

BACKGROUND & AIMS: Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension-related decompensation in patients with advanced NAFLD (aNAFLD). METHODS: Multicenter cross-sectional study included 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels. RESULTS: Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and Model for End-Stage Liver Disease score. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25%; P = .019) than in the aHCV group. For any of the HVPG cutoff analyzed (<10, 10-12, or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD group than in the aHCV group. CONCLUSIONS: Patients with aNAFLD have higher prevalence of portal hypertension-related decompensation at any value of HVPG as compared with aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed.

National digestive disease specialists survey on cardiovascular risk management in non-alcoholic fatty liver disease in spanish hospitals.

BACKGROUND & AIMS: Cardiovascular disease (CVD) is the main cause of mortality among non-alcoholic fatty liver disease (NAFLD) patients. The aim was to explore the level of knowledge and clinical management of cardiovascular risk (CVR) in NAFLD patients by Digestive Disease specialists. METHODS: An anonymous web-based survey was designed with 44 close-ended questions, divided into five sections, that were based on current guidelines on CVD prevention. Between November 2019 and January 2020, Digestive Disease specialists from Spanish hospitals were invited to participate in this survey via email and Twitter. Student's t, chi-square and Fishers' exact tests, and logistic regression were used for data analysis. RESULTS: 208 clinicians completed the survey. Most respondents (83.2%) believe that NAFLD is an independent risk factor for CVD, especially in the presence of NASH and fibrosis. Personal history of CVDs and cardiovascular risk-related comorbidities are collected by more than 75% of respondents. However, less than 17% perform an elementary physical examination to address the CVR, except weight which is evaluated by 69.8%. Over 54% of respondents do not perform or request any supplementary tests for CVR assessment, and only 10.2% use specific calculators. Furthermore, 54.3% spend less than 5 minutes giving lifestyle advice, and more than 52% do not start drug treatment after a recent diagnosis of any cardiovascular comorbidity. Only 25.6% have a multidisciplinary Unit for metabolic comorbidities in their hospitals, although 89% of the respondents would support the implementation of this Unit. CONCLUSIONS: Cardiovascular risk management in daily clinical practice by Digestive Disease specialists in Spain remains suboptimal.

Clinical outcome and hemodynamic changes following HCV eradication with oral antiviral therapy in patients with clinically significant portal hypertension.

BACKGROUND & AIMS: Clinically significant portal hypertension (CSPH), defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, persists 24 weeks after sustained virological response (SVR) in up to 78% of patients with HCV-related cirrhosis treated with direct-acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population. METHODS: We conducted a prospective multicenter study in 226 patients with HCV-related cirrhosis and CSPH who achieved SVR after antiviral therapy. Patients with CSPH 24 weeks after end of treatment (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96). RESULTS: All patients were clinically evaluated. Out of 176 patients with CSPH at SVR24, 117 (66%) underwent an HVPG measurement at SVR96. At SVR96, 55/117 (47%) patients had HVPG <10 mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥16 mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13 kPa) but did not correlate with HVPG changes (30% of patients with liver stiffness measurement <13.6 kPa still had CSPH). Seventeen (7%) patients presented with de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥16 mmHg and history of ascites. CONCLUSIONS: Patients achieving SVR experienced a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53-65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation. LAY SUMMARY: As a major complication of cirrhosis, clinically significant portal hypertension (CSPH) is associated with adverse clinical outcomes. Herein, we show that CSPH persists at 96 weeks in just over half of patients with HCV-related cirrhosis, despite HCV elimination by direct-acting antivirals. Despite viral cure, patients with CSPH at the start of antiviral treatment remain at long-term risk of hepatic complications and should be managed accordingly.

Update on epidemiology of hepatitis B in a low-endemic European country: There is still much to do.

The latest epidemiological data in Spain were obtained a decade ago and revealed a prevalence of hepatitis B surface antigen (HBsAg) of 0.7%; hence, updated epidemiological data are necessary. Our aim was to determine the prevalence of hepatitis B virus (HBV) infection, and to analyse associated factors and characterize chronic infection. A population-based, cross-sectional study was performed in Spain between July 2015 and April 2017. Participants from three regions were selected using two-stage conglomerate sampling and stratified by age. Anthropometric and demographic data were collected, and blood samples were taken to detect serological markers of HBV infection and to quantify HBV-DNA. The characterization of chronic HBV infection was based on ALT (alanine aminotransferase) values, HBV-DNA levels, and results of transient elastography. The overall prevalence rates of HBsAg and antibody to hepatitis B core antigen (anti-HBc) among 12 246 participants aged 20-74 years (58.4% females) were 0.6% (95% CI [0.4-0.7]) and 8.2% (7.7-8.7), respectively. The risk factors for HBV infection identified in the multivariate analysis were age, nosocomial risk, and non-Spanish nationality. Moreover, most patients HBsAg positive (76.6%) presented as hepatitis B e antigen (HBeAg)-negative chronic infection (formerly 'inactive carriers') and only 6 (9.4%) HBsAg carriers fulfilled current criteria for treatment. The current HBV burden in Spain remains low but virtually unchanged over the past 15 years. Increased efforts are still needed to reach the goal set forth by the World Health Organization (WHO) for HBV elimination by 2030.

Congestive Hepatopathy.

Liver disease resulting from heart failure (HF) has generally been referred as "cardiac hepatopathy". One of its main forms is congestive hepatopathy (CH), which results from passive venous congestion in the setting of chronic right-sided HF. The current spectrum of CH differs from earlier reports with HF, due to ischemic cardiomyopathy and congenital heart disease having surpassed rheumatic valvular disease. The chronic passive congestion leads to sinusoidal hypertension, centrilobular fibrosis, and ultimately, cirrhosis ("cardiac cirrhosis") and hepatocellular carcinoma after several decades of ongoing injury. Contrary to primary liver diseases, in CH, inflammation seems to play no role in the progression of liver fibrosis, bridging fibrosis occurs between central veins to produce a "reversed lobulation" pattern and the performance of non-invasive diagnostic tests of liver fibrosis is poor. Although the clinical picture and prognosis is usually dominated by the underlying heart condition, the improved long-term survival of cardiac patients due to advances in medical and surgical treatments are responsible for the increased number of liver complications in this setting. Eventually, liver disease could become as clinically relevant as cardiac disease and further complicate its management.

Prevalence of hepatitis C in patients with non-affective psychotic disorders.

INTRODUCTION: the goal of this study was to determine the prevalence of hepatitis C virus (HCV) infection in patients with non-affective psychotic disorders and to compare it with population-based data. MATERIAL AND METHODS: an observational study was performed that measured anti-HCV antibodies (HCV-RNA in case of seropositivity) in 425 serum samples from patients with non-affective psychosis. Eight patients were positive for anti-HCV (1.9 %) and five had detectable HCV-RNA (1.2 %). The prevalence of viremia was significantly higher than in the general population (OR: 5.4; 95 % CI: 1.9-14.6). CONCLUSIONS: patients with non-affective psychotic disorder have a higher prevalence of active infection than that of the general population and should undergo systematic screening.

LOXL2-A New Target in Antifibrogenic Therapy?

The concept of liver fibrosis and cirrhosis being static and therefore irreversible is outdated. Indeed, both human and animal studies have shown that fibrogenesis is a dynamic and potentially reversible process that can be modulated either by stopping its progression and/or by promoting its resolution. Therefore, the study of the molecular mechanisms involved in the pathogenesis of liver fibrosis is critical for the development of future antifibrotic therapies. The fibrogenesis process, common to all forms of liver injury, is characterized by the increased deposition of extracellular matrix components (EMCs), including collagen, proteoglycans, and glycoproteins (laminin and fibronectin 2). These changes in the composition of the extracellular matrix components alter their interaction with cell adhesion molecules, influencing the modulation of cell functions (growth, migration, and gene expression). Hepatic stellate cells and Kupffer cells (liver macrophages) are the key fibrogenic effectors. The antifibrogenic mechanism starts with the activation of Ly6Chigh macrophages, which can differentiate into macrophages with antifibrogenic action. The research of biochemical changes affecting fibrosis irreversibility has identified lysyl oxidase-like 2 (LOXL2), an enzyme that promotes the network of collagen fibers of the extracellular matrix. LOXL2 inhibition can decrease cell numbers, proliferation, colony formations, and cell growth, and it can induce cell cycle arrest and increase apoptosis. The development of a new humanized IgG4 monoclonal antibody against LOXL2 could open the window of a new antifibrogenic treatment. The current therapeutic target in patients with liver cirrhosis should focus (after the eradication of the causal agent) on the development of new antifibrogenic drugs. The development of these drugs must meet three premises: Patient safety, in non-cirrhotic phases, down-staging or at least stabilization and slowing the progression to cirrhosis must be achieved; whereas in the cirrhotic stage, the objective should be to reduce fibrosis and portal pressure.

Effects of All-Oral Anti-Viral Therapy on HVPG and Systemic Hemodynamics in Patients With Hepatitis C Virus-Associated Cirrhosis.

BACKGROUND & AIMS: Patients with hepatitis C virus-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH. METHODS: We performed a multicenter prospective study of 226 patients with hepatitis C virus-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain. The portal pressure gradient was determined based on HVPG at baseline and 24 weeks after therapy; patients also underwent right-heart catheterization and LSM at these time points. Primary outcomes were effects of SVR on the hepatic, pulmonary, and systemic hemodynamics; factors related to HVPG ≥10% reduction and to CSPH persistence; and whether LSMs can rule out the presence of CSPH after SVR. RESULTS: Most patients (75%) had esophageal varices, 21% were Child-B, and 29% had at least 1 previous episode of liver decompensation. Overall, HVPG decreased from 15 (IQR: 12-18) before treatment to 13 (10-16) mmHg after SVR (reduction of 2.1 ± 3.2 mmHg; P < .01). However, CSPH persisted in 78% of patients. HVPG decreased by 10% or more from baseline in 140 patients (62%). Baseline level of albumin below 3.5 g/dL was the only negative factor associated with an HVPG reduction of 10% or more. LSM decreased from 27 (20-37) kPa before treatment to 18 (14-28) kPa after SVR (P < .05). One third of patients with a reduction in LSM to below 13.6 kPa after SVR still had CSPH. A higher baseline HVPG and a lower decrease in LSM after treatment were associated with persistence of CSPH after SVR. Systemic hemodynamics improved after SVR. Interestingly, pulmonary hypertension was present in 13 patients at baseline and 25 after SVR, although only 3 patients had increased pulmonary resistance. CONCLUSIONS: In a multicenter prospective study of patients with hepatitis C virus-associated cirrhosis, an SVR to all-oral therapy significantly reduced HVPG, compared with before treatment. Nevertheless, CSPH persists in most patients despite SVR, indicating persistent risk of decompensation. In this population, changes in LSM do not correlate with HVPG and cut-off values are not reliable in ruling out CSPH after SVR.

Microenvironment Eradication of Hepatitis C: A Novel Treatment Paradigm.

OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Our aim was to create a permanent program of HCV elimination in a prison based on a "test and treat" strategy. METHODS: This open-label clinical trial was conducted in the Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015 Spanish Guidelines. A teleconsultation program was established to follow-up patients from the hospital. Non-responders were submitted for a phylogenetic analysis and offered retreatment. An evaluation of new cases of HCV infection was performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%) inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and 86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and had

Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy.

BACKGROUND AND AIMS: The regression of liver fibrosis and portal hypertension (PH) and their influence on the natural history of compensated hepatitis C virus (HCV)-related cirrhosis has not been studied previously. Our objective was to evaluate the influence of sustained virologic response (SVR) on the portal pressure gradient (HVPG) and non-invasive parameters of PH and prognostic factors of response. METHODS: Sixteen patients with compensated HCV genotype 1-related cirrhosis with PH (HVPG > 6 mmHg) without beta-blocker therapy were considered as candidates for PEGα2a + RBV + BOC (48 weeks; lead-in and accepted stopping rules). A hemodynamic study and Fibroscan® were performed at baseline, at eight weeks and, in the case of SVR, 24 weeks after treatment. In each hemodynamic study, serum samples were analyzed for inflammatory biomarkers associated with PH. RESULTS: In eight cases, SVR was obtained; five patients relapsed, and treatment was stopped early for non-response to lead in (one case) and a decrease of < 3 log at week 8 (two patients). Compared to baseline, there was a significant decrease in HVPG and Fibroscan® at weeks 8 and 72 (10.31 ± 4.3 vs 9.4 ± 5.04 vs 6.1 ± 3.61 mmHg, p < 0.0001 and 21.3 ± 14.5 vs 16.2 ± 9.5 vs 6.4 ± 4.5 kPa, p < 0.0001, respectively). The average HVPG decrease in SVR was 40.8 ± 17.53%, achieving an HVPG < 6 mmHg in five patients (62.5%) and a Fibroscan® < 7.1 kPa in three patients (37.5%). CONCLUSIONS: Complete hemodynamic response (HVPG < 6 mmHg) and fibrosis regression (Fibroscan® < 7.1 kPa) occur in more than half and one-third of patients achieving SVR, respectively, and must be another target in cirrhotic patients with SVR.

No evidence of association between inherited thrombophilia and increased risk of liver fibrosis.

BACKGROUND: Preliminary evidence suggests that inherited hypercoagulable disorders can lead to an increased risk of significant liver fibrosis. OBJECTIVE: We aimed to investigate the prevalence of significant fibrosis in patients with inherited thrombophilia, assessed by using liver stiffness (LS), and to compare this prevalence to that found in a large population-based cohort from the same region. METHODS: This was a single-center, cross-sectional study. A complete laboratory analysis for liver disease, LS by transient elastography and an abdominal ultrasound were performed in patients with inherited thrombophilia diagnosed between May 2013-February 2017. These patients were propensity score matched (ratio 1:4) with a population-based cohort from the same region (PREVHEP-ETHON study; NCT02749864; N = 5988). RESULTS: Of 241 patients with inherited thrombophilia, eight patients (3.3%) had significant fibrosis (LS ≥8 kPa). All of them had risk factors for liver disease and met diagnostic criteria for different liver diseases. After matching 221 patients with thrombophilia with 884 patients of the PREVHEP-ETHON cohort, the prevalence of significant fibrosis was similar between both cohorts (1.8% vs. 3.6%, p = 0.488). Multivariate analysis showed that age and liver disease risk factors, but not belonging to the thrombophilia cohort, were associated with the presence of significant fibrosis. The magnitude of the increased risk of significant fibrosis in patients with risk factors for liver disease was also similar in both cohorts. CONCLUSIONS: Our findings do not provide evidence supporting an association between inherited thrombophilia and an increased risk of significant liver fibrosis, independent of the presence of liver-related causes of fibrosis.

Risk of Recurrence of Hepatocarcinoma after Liver Transplantation: Performance of Recurrence Predictive Models in a Cohort of Transplant Patients.

Liver transplantation (LT) is a curative treatment for early-stage hepatocellular carcinoma (HCC) unsuitable for surgical resection. However, tumor recurrence (TR) rates range from 8% to 20% despite strict selection criteria. The validation of new prognostic tools, such as pre-MORAL or RETREAT risks, is necessary to improve recurrence prediction. A retrospective study was conducted at Marqués de Valdecilla University Hospital in Cantabria, Spain, between 2010 and 2019 to determine the rate of TR in LT patients and identify associated factors. Patients with liver-kidney transplantation, re-transplantation, HIV infection, survival less than 90 days, or incidental HCC were excluded. Data on demographic, liver disease-related, LT, and tumor-related variables, as well as follow-up records, including TR and death, were collected. TR was analyzed using the Log-Rank test, and a multivariate Cox regression analysis was performed. The study was approved by the IRB of Cantabria. TR occurred in 13.6% of LT patients (95% CI = 7.3-23.9), primarily as extrahepatic recurrence (67%) within the first 5 years (75%). Increased TR was significantly associated with higher Body Mass Index (BMI) (HR = 1.3 [95% CI = 1.1-1.5]), vascular micro-invasion (HR = 8.8 [1.6-48.0]), and medium (HR = 20.4 [3.0-140.4]) and high pre-MORAL risk (HR = 30.2 [1.6-568.6]). TR also showed a significant correlation with increased mortality. Conclusions: LT for HCC results in a 13.6% rate of tumor recurrence. Factors such as BMI, vascular micro-invasion, and medium/high pre-MORAL risk are strongly associated with TR following LT.

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.

Cirrhosis, a Global and Challenging Disease.

Cirrhosis is the result of sustained liver damage leading to the diffusion of hepatic fibrosis, wherein the normal hepatic architecture is replaced by abnormally organized nodules separated by fibrous septa that connect the different vascular structures of the hepatic lobule [...].