Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

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.

Comparison of non-invasive fibrosis scores to predict increased liver stiffness in the general population with unknown liver disease: Searching for the primary physician's best friend.

BACKGROUND: Serum-based scores (SBS) appear to be a high applicability strategy for assessment of liver fibrosis in primary care. Aim of the study was to evaluate their performance to detect ≥F2 in a general population and to design a highly-applicable strategy for screening. METHODS: prospective population-based cohort study in randomly identified subjects, aged 40-70y. Medical history, blood tests and elastography were obtained, ≥F2 was determined by using LSM cutoff ≥9.2/7.8 kPa for M/XL probe and SBS diagnostic accuracies were evaluated. RESULTS: 986 patients were analyzed. LSM prevalence estimate suggestive of ≥F2 was 1.9% and Metabolic Sindrome (MS) (OR 3.4, 1.3-9.0;p = 0.01), was the only factor independently associated with ≥F2, with increasing prevalence according to the number of criteria (0 criterion:0%,1:0.3%,2:2.8%,3:2.4%,4:6.9%,5:14.3%;p<0.001). FLI and NFS were the two best-performing tests in the cross-sectional study, with AUROCs for ≥F2 of 0.89 (95%CI,0.84- 0.95) and 0.82 (95%CI,0.74-0.90), respectively. Predefined cutoff for FLI≥60 (Sn89.5%, Sp72.1%, NPV99.9%) and NFS≥-1.455 (Sn83.3%, Sp68%, NPV99.6%) showed adequate diagnostic accuracy. Based on these findings, a 3- step algorithm strategy to detect liver fibrosis in the community setting is proposed (Sn84.2%, Sp75.2%, NVP99.6%). CONCLUSIONS: A staged risk-stratification model improves the detection of ≥F2 in the community setting, while reducing unnecessary referrals.

Non-malignant portal vein thrombosis in a cohort of cirrhotic patients: Incidence and risk factors.

AIM: Non-malignant portal vein thrombosis (PVT) is a complication of liver cirrhosis. The aim of this study was to evaluate the annual incidence of PVT and related risk factors. METHODS: We retrospectively reviewed clinical, laboratory, and radiological data collected prospectively from September 2016 to September 2017. A follow-up of 36 months was performed in a subset of patients to determine the cumulative incidence of PVT and related complications. RESULTS: The study included 567 patients. The incidence of PVT at 12, 24, and 36 months was 3.7%, 0.8%, and 1.4%, respectively. Patients with PVT were compared with patients without PVT, and showed differences in albumin (p = 0.04), aspartate aminotransferase (p = 0.04), hemoglobin (p = 0.01), and prothrombin activity (p = 0.01). The presence of hydropic decompensation (57.1% vs. 30.1%; p 0.004), gastroesophageal varices (76.2% vs. 39.5%; p = 0.05), variceal bleeding (52.4% vs. 22.7%; p < 0.001), hepatic encephalopathy (38.1% vs. 9.9%; p = 0.01), spontaneous bacterial peritonitis (9.5% vs. 1.7%; p < 0.001), and use of beta-blockers (71.4% vs. 27.7%; p < 0.001) were significantly associated. In the multivariate analysis, use of beta-blockers and hepatic encephalopathy appeared as risk factors, and high albumin levels a protective factor. CONCLUSIONS: The incidence of PVT was 3.7%. Beta-blockers and hepatic encephalopathy were risks factors. High albumin levels were a protective factor.

Estimation of visceral fat is useful for the diagnosis of significant fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), although obese patients with NAFLD do not always develop significant fibrosis. The distribution of body fat could predict the risk of NAFLD progression. AIM: To investigate the role of bioelectrical impedance-estimated visceral fat (VF) in assessing NAFLD severity. METHODS: In this cross-sectional study, patients with biopsy-proven NAFLD were prospectively included. All patients underwent anthropometric evaluation, blood tests and bioelectrical impedance analysis. RESULTS: Between 2017 and 2020, 119 patients were included [66.4% male, 56 years (SD 10.7), 62.2% obese, 61.3% with metabolic syndrome]. Sixty of them (50.4%) showed significant fibrosis (≥ F2) in liver biopsy. Age, VF and metabolic syndrome were associated with significant fibrosis (61 years vs 52 years, 16.4 vs 13.1, 73.3% vs 49.2%, respectively; P < 0.001 for all). In the multivariate analysis, VF and age were independently associated with significant fibrosis (VF, OR: 1.11, 95%CI: 1.02-1.22, P = 0.02; age, OR: 1.08, 95%CI: 1.03-1.12, P < 0.01). A model including these variables showed and area under the receiver operating characteristic curve (AUROC) of 0.75, which was not inferior to transient elastography or NAFLD fibrosis score AUROCs. We developed a nomogram including age and VF for assessing significant fibrosis in routine practice. CONCLUSION: VF is a surrogate marker of liver fibrosis in patients with NAFLD. Bioelectrical impedance analysis is an inexpensive and simple method that can be combined with age to guide patient referral when other resources may be unavailable.

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.

Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): An International Observational Study.

Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.

Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort.

BACKGROUND & AIMS: Fontan surgery is used to treat a variety of congenital heart malformations, and may lead to advanced chronic liver disease in the long-term. This study examines the prevalence, characteristics and predictors of liver nodules in patients following Fontan surgery. METHODS: This was a prospective, cross-sectional, observational study conducted at 8 European centres. Consecutive patients who had undergone Fontan surgery underwent blood tests, abdominal ultrasonography (US), transient elastography (Fibroscan®), echocardiography, haemodynamic assessments, and abdominal MRI/CT scan. The primary outcome measure was liver nodules detected in the MRI/CT scan. Predictors of liver nodules were identified by multivariate logistic regression. RESULTS: One hundred and fifty-two patients were enrolled (mean age 27.3 years). The mean time elapsed from surgery to inclusion was 18.3 years. Liver nodule prevalences were 29.6% (95% CI 23-37%) on US and 47.7% (95% CI 39-56%) on MRI/CT. Nodules were usually hyperechoic (76.5%), round-shaped (>80%), hyperenhancing in the arterial phase (92%) and located in the liver periphery (75%). The sensitivity and specificity of US were 50% (95% CI 38-62%) and 85.3% (95% CI 75-92%), respectively. Inter-imaging test agreement was low (adjusted kappa: 0.34). In the multivariate analysis, time since surgery >10 years was the single independent predictor of liver nodules (odds ratio 4.18; p = 0.040). Hepatocellular carcinoma was histologically diagnosed in 2 of the 8 patients with hypervascular liver nodules displaying washout. CONCLUSION: While liver nodules are frequent in Fontan patients, they may go unnoticed in US. Liver nodules are usually hyperechoic, hypervascular and predominantly peripheral. This population is at risk of hepatocellular carcinoma, the diagnosis of which requires confirmatory biopsy. LAY SUMMARY: Fontan surgery is the standard of care for many patients with univentricular congenital cardiopathies. Recent advances have improved the survival of Fontan patients, and nowadays most of them reach adulthood. In this setting, Fontan-associated liver disease (FALD) is increasingly recognised, and has become a significant prognostic factor. Liver nodules are considered a component of FALD yet their prevalence, imaging features and predictors have hardly been evaluated. In this study, we observed that liver nodules are frequent, typically hyperechoic, hypervascular and predominantly peripheral in patients with FALD. This population is at risk of hepatocellular carcinoma, the diagnosis of which must be confirmed by biopsy.

The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery.

BACKGROUND & AIMS: Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. METHODS: A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002-2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1 year and mortality, transplantation, morbidity and post-surgical decompensation were studied. RESULTS: Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16 mmHg were independently associated with mortality and values ≥20 mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3 months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG <10 mmHg or indocyanine green clearance >0.63 developed decompensation. CONCLUSIONS: ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16 mmHg, especially ≥20 mmHg, were associated with a high risk of post-surgical mortality. LAY SUMMARY: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.

Impact of sustained viral response in the evolution of minimal hepatic encephalopathy: A prospective pilot study.

INTRODUCTION AND AIMS: To determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. MATERIALS AND METHODS: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. RESULTS: 64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p<0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p=0.02), higher Child-Pugh scores at 24-weeks post-treatment (p=0.04), higher baseline INR levels (1.4 vs. 1.1; p<0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p=0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p=0.04). CONCLUSION: We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.

Noncirrhotic portal hypertension: An under-reported late adverse event of SIRT in metastatic colorectal cancer patients.

INTRODUCTION: Selective internal radiation therapy (SIRT) is increasingly used in different scenarios. Although portal hypertension (PHT) has been described as a nonclinically relevant finding after SIRT, its real incidence could have been neglected due to the nature of the diseases for which SIRT is indicated. CASE REPORTS: Here we report three cases with clinically relevant late PHT after treatments including SIRT and oxaliplatin among others. DISCUSSION: The sequential use of oxaliplatin and SIRT in patients with colorectal cancer metastases could have additive effects on the liver.

Validation of noninvasive methods to predict the presence of gastroesophageal varices in a cohort of patients with compensated advanced chronic liver disease.

BACKGROUND AND AIM: The aim was to validate noninvasive methods to predict the presence of gastroesophageal varices (GEV) in patients with suspected compensated advanced chronic liver disease. METHODS: We retrospectively reviewed clinical and radiological data collected prospectively between September 2013 and September 2015. We reviewed 442 consecutive patients with suspected compensated advanced chronic liver disease measured by transient elastography (TE) and a gastroscopy. We evaluated platelets, spleen diameter, TE, liver stiffness × spleen size/platelets (LSPS), variceal risk index (VRI), Baveno VI strategy, and Augustin algorithm. RESULTS: One hundred sixty-one out of 442 patients were included. Patients with GEV were compared with patients without GEV and showed statistically significant differences in platelet count (117 SD 51 vs 149 SD 62; P = 0.02), spleen diameter (13.0 SD 1.9 vs 11.5 SD 2; P = 0.003), and TE (28 SD 15 vs 19 SD 10; P = 0.001). Single methods (platelet count and TE) diagnosed correctly 51% and 71.4% of patients. Combined methods (LSPS, VRI, Baveno VI, and Augustin algorithm) diagnosed correctly 78%, 83.6%, 45.3%, and 57.1% of patients. Patients with GEV misdiagnosed: platelets 5/161 (3.1%), TE 6/161 (3.7%), LSPS 16/159 (10%), VRI 18/159 (11.3%), Baveno VI 3/161 (1.8%), and Augustin algorithm 6/161 (3.7%). Rate of unnecessary gastroscopies: platelets 46%, TE 25%, LSPS 13%, VRI 6%, Baveno VI 53%, and Augustin algorithm 39.1%. CONCLUSIONS: A significant number of patients were classified correctly using TE, LSPS, and VRI; however, LSPS and VRI had unacceptable rates of misdiagnoses. TE is the best noninvasive single method and the Baveno VI strategy the best combined method.

[Treatment of non-cirrhotic, non-tumoural portal vein thrombosis]. / Actuación ante la trombosis portal no cirrótica no tumoral.

Thrombosis of the splenoportal axis not associated with liver cirrhosis or neoplasms is a rare disease whose prevalence ranges from 0.7 to 3.7 per 100,000 inhabitants. However, this entity is the second most common cause of portal hypertension. Prothrombotic factors are present as an underlying cause in up to 70% of patients and local factors in 10-50%. The coexistence of several etiological factors is frequent. Clinical presentation may be acute or chronic (portal cavernomatosis). The acute phase can present as abdominal pain, nausea, vomiting, fever, rectorrhagia, intestinal congestion, and ischemia. In this phase, early initiation of anticoagulation is essential to achieve portal vein recanalization and thus improve patient prognosis. In the chronic phase, symptoms are due to portal hypertension syndrome. In this phase, the aim of treatment is to treat or prevent the complications of portal hypertension. Anticoagulation is reserved to patients with a proven underlying thrombophilic factor.

A MELD-based model to determine risk of mortality among patients with acute variceal bleeding.

BACKGROUND & AIMS: Patients with cirrhosis with acute variceal bleeding (AVB) have high mortality rates (15%-20%). Previously described models are seldom used to determine prognoses of these patients, partially because they have not been validated externally and because they include subjective variables, such as bleeding during endoscopy and Child-Pugh score, which are evaluated inconsistently. We aimed to improve determination of risk for patients with AVB. METHODS: We analyzed data collected from 178 patients with cirrhosis (Child-Pugh scores of A, B, and C: 15%, 57%, and 28%, respectively) and esophageal AVB who received standard therapy from 2007 through 2010. We tested the performance (discrimination and calibration) of previously described models, including the model for end-stage liver disease (MELD), and developed a new MELD calibration to predict the mortality of patients within 6 weeks of presentation with AVB. MELD-based predictions were validated in cohorts of patients from Canada (n = 240) and Spain (n = 221). RESULTS: Among study subjects, the 6-week mortality rate was 16%. MELD was the best model in terms of discrimination; it was recalibrated to predict the 6-week mortality rate with logistic regression (logit, -5.312 + 0.207 • MELD; bootstrapped R(2), 0.3295). MELD values of 19 or greater predicted 20% or greater mortality, whereas MELD scores less than 11 predicted less than 5% mortality. The model performed well for patients from Canada at all risk levels. In the Spanish validation set, in which all patients were treated with banding ligation, MELD predictions were accurate up to the 20% risk threshold. CONCLUSIONS: We developed a MELD-based model that accurately predicts mortality among patients with AVB, based on objective variables available at admission. This model could be useful to evaluate the efficacy of new therapies and stratify patients in randomized trials.

Rebleeding prophylaxis improves outcomes in patients with hepatocellular carcinoma. A multicenter case-control study.

UNLABELLED: Outcome of variceal bleeding (VB) in patients with hepatocellular carcinoma (HCC) is unknown. We compared outcomes after VB in patients with and without HCC. All patients with HCC and esophageal VB admitted between 2007 and 2010 were included. Follow-up was prolonged until death, transplantation, or June 2011. For each patient with HCC, a patient without HCC matched by age and Child-Pugh class was selected. A total of 292 patients were included, 146 with HCC (Barcelona Classification of Liver Cancer class 0-3 patients, A [in 25], B [in 29], C [in 45], and D [in 41]) and 146 without HCC. No differences were observed regarding previous use of prophylaxis, clinical presentation, endoscopic findings, and initial endoscopic treatment. Five-day failure was similar (25% in HCC versus 18% in non-HCC; P = 0.257). HCC patients had greater 6-week rebleeding rate (16 versus 7%, respectively; P = 0.025) and 6-week mortality (30% versus 15%; P = 0.003). Fewer patients with HCC received secondary prophylaxis after bleeding (77% versus 89%; P = 0.009), and standard combination therapy was used less frequently (58% versus 70%; P = 0.079). Secondary prophylaxis failure was more frequent (50% versus 31%; P = 0.001) and survival significantly shorter in patients with HCC (median survival: 5 months versus greater than 38 months in patients without HCC; P < 0.001). Lack of prophylaxis increased rebleeding and mortality. On multivariate analysis Child-Pugh score, presence of HCC, portal vein thrombosis, and lack of secondary prophylaxis were predictors of death. CONCLUSIONS: Patients with HCC and VB have worse prognosis than patients with VB without HCC. Secondary prophylaxis offers survival benefit in HCC patients.

Assessment of portal hypertension by transient elastography in patients with compensated cirrhosis and potentially resectable liver tumors.

BACKGROUND & AIMS: Patients with cirrhosis and small hepatocellular carcinoma with normal bilirubin and hepatic venous pressure gradient (HVPG) <10 mm Hg have >70% 5-year survival after hepatic resection. On the contrary, patients with HVPG ≥10 mm Hg (clinically significant portal hypertension, CSPH) frequently develop decompensation following surgery, with around 50% 5-year survival. Liver stiffness (LS) evaluation by transient elastography might non-invasively identify CSPH. We investigated the usefulness of LS predicting CSPH in patients with compensated cirrhosis and potentially resectable liver tumors. METHODS: Ninety-seven consecutive Child-Pugh A patients with potentially resectable liver tumors referred for HVPG measurement were prospectively evaluated. In fasting conditions LS was measured before the hemodynamic study. RESULTS: HVPG could be measured in all patients, whereas LS could not be measured in 18 (18.5%) obese patients. In the 79 patients with valid LS, 32 (40.5%) had CSPH; mean HVPG was 8.8±4.7 mm Hg. Mean LS was 18.4±12.3 kPa. LS showed a moderate correlation with HVPG (r=0.552; p<0.001). LS<13.6 kPa had high sensitivity (91%) but low specificity (57%) excluding CSPH. Conversely, LS>21 kPa had low sensitivity (53%) and high specificity (91%) predicting CSPH. 35% of patients had LS between 13.6 and 21 kPa ("grey zone"). CONCLUSIONS: These data suggest that in real-life scenarios half of patients with potentially resectable liver nodules can be non-invasively classified as having or not CSPH by LS. However, in the remaining half, LS is either not applicable or inaccurate. In this last population HVPG is still a non replaceable method to detect CSPH.

Portal cholangiopathy: radiological classification and natural history.

BACKGROUND/AIM: Portal cholangiopathy (PC) is identified in over 80% of patients with portal vein thrombosis (PVT), but the true impact of this condition is not well known. This study investigated the relationship between cholangiographic abnormalities and clinical symptoms and their evolution over time. PATIENTS/METHODS: 67 consecutive patients with non-tumoral non-cirrhotic PVT following a standardised diagnostic protocol were studied. Findings at magnetic resonance angiography and cholangiography (MRA/MRC) were classified as no PC, grade I PC (minimal irregularities), grade II PC (stenosis without dilation) and grade III PC (stenosis with dilation). These changes were related to the presence of symptoms. RESULTS: 22 patients were diagnosed with acute PVT and 45 presented with chronic PVT. Overall, 52 patients had PC (6 grade I, 12 grade II and 34 grade III). 14 patients developed symptoms, all of whom had grade III PC. 30% of patients with acute PVT developed grade III PC within 1 year. In those without grade III PC, follow-up MRC showed no progression of the biliary lesions to grade III. The 5-year probability of developing symptoms of PC after acute PVT was 19%. In 45 patients with chronic PVT, MRA/MRC showed grade III PC in 26. In those without grade III PC, no progression of PC was observed at further follow-up MRC. The prevalence of symptoms of PC in these patients was 22%. CONCLUSIONS: PC is a frequent complication that develops and stabilises early after PVT and becomes symptomatic in its more severe form (grade III). These data suggest that follow-up MRA/MRC is not mandatory and strategies to prevent the development of symptoms of PC should be tested in patients with grade III PC.