International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Predicting bleeding after liver biopsy using comprehensive clinical and laboratory investigations: A prospective analysis of 302 procedures.

BACKGROUND: Liver biopsy carries a small risk of bleeding complications. No validated clinical or laboratory tool helps predict liver biopsy-related bleeding. OBJECTIVES: To determine whether global hemostasis tests and/or a clinical questionnaire could identify patients at risk of liver biopsy-related bleeding. PATIENTS/METHODS: Consecutive patients scheduled for liver biopsy with an overnight hospital stay were prospectively included. Before liver biopsy, routine hemostasis tests, Platelet Function Analyzer 100, thromboelastometry, thrombin generation assay, plasma clot lysis time, and a clinical questionnaire were performed. Bleeding was defined as a liver hematoma or new free fluid on a systematic ultrasound performed 24 h after liver biopsy or a decrease in hemoglobin level of 2 g/dL or more in patients with pre-existing free fluid in the abdominal cavity. RESULTS: Three hundred two patients were included: 173 underwent percutaneous and 129 transjugular liver biopsy. There were 21 bleeding episodes (7%); 20 based on ultrasonographic criteria, 1 on laboratory criteria. None of the hemostasis tests and no item of the clinical questionnaire were associated with liver biopsy-related bleeding in the overall study group. Same results were obtained in subgroup analyses focusing on patients who underwent percutaneous liver biopsy, transjugular liver biopsy, or on patients with cirrhosis. Pain 2 h after liver biopsy was more frequent in patients with liver biopsy-related bleeding (55% vs. 23% p = .002). CONCLUSIONS: An extensive hemostasis workup, including global hemostasis assays, does not improve prediction of liver biopsy-related bleeding. Pain 2 h after liver biopsy should alert the clinician to the possibility of procedure-related bleeding.

A real-world experience of SARS-CoV-2 infection in a tertiary referral centre of Montréal: Unexpected low prevalence and low mortality.

BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centre hospitalier de l'Université de Montréal (CHUM) during the first wave of the SARS-CoV-2 pandemic. METHODS: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection. Cases were considered positive as defined by the detection of SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. RESULTS: Between April 1 and July 31, 2020, 5,637 were admitted to our liver unit and/or seen as outpatient. Among them, 42 were positive for SARS-CoV-2. Twenty-two patients had CLD without cirrhosis while 16 patients had cirrhosis at the time of the infection (13, 2, and 1 with Child-Pugh A, B, and C scores, respectively). Four were LT recipients. Overall, 15 of 42 patients (35.7%) were hospitalized; among them, 7 of 42 (16.7%) required respiratory support and 4 of 42 (9.5%) were transferred to the intensive care unit. Only 4 of 42 (9.5%) patients died: 2 with CLD without cirrhosis and 2 with CLD with cirrhosis. Overall survival was 90.5%. CONCLUSION: This real-world study demonstrates an unexpectedly low prevalence and low mortality in the context of SARS-CoV-2 infection among patients with CLD with or without cirrhosis and LT recipients.

Hepatocyte microvesicle levels improve prediction of mortality in patients with cirrhosis.

Microvesicles (MVs) are extracellular vesicles released by cells following activation or apoptosis. Some MV subpopulations augment with cirrhosis severity and contribute to portal hypertension. This study aimed at determining if plasma MV levels can estimate the presence of hepatic venous pressure gradient (HVPG) ≥10 mm Hg and predict mortality in patients with advanced chronic liver disease. All patients with severe fibrosis or cirrhosis undergoing liver catheterization between 2013 and 2015 at two centers were prospectively included. We measured circulating levels of annexin V+ , platelet, leukocyte, endothelial, and hepatocyte MVs. The test cohort included 139 patients. Hepatocyte MV levels were 4.0-fold and 2.2-fold higher in patients with Child-Pugh C than in those with Child-Pugh A or B liver disease, respectively. Levels of other MV subpopulations were not influenced by liver disease severity. Hepatocyte MV levels correlated with HVPG but could not identify patients with HVPG ≥10 mm Hg. Hepatocyte MV level >65 U/L predicted 6-month mortality independently of Child-Pugh score and of Model for End-Stage Liver Disease (MELD). Patients with hepatocyte MV levels >65 U/L and MELD >15 had a higher 6-month mortality than other patients (23% versus 3%; P = 0.001). These findings were confirmed in a validation cohort including 103 patients. CONCLUSION: Circulating MV levels cannot identify patients with HVPG ≥10 mm Hg; by contrast, hepatocyte MV levels strongly improve prediction of 6-month mortality in patients with advanced chronic liver disease; therapies associated with decreased levels of circulating hepatocyte MV might be attractive strategies in patients with severe cirrhosis. (Hepatology 2018).

Assessment of the spectrum of hepatic encephalopathy: A multicenter study.

Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However, its severity assessment is often subjective, which needs to be studied systematically. The aim was to determine how accurately trainee and nontrainee practitioners grade and manage HE patients throughout its severity. We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and nontrainees (faculty, nurse practitioners, physician assistants). We determined the accuracy of HE severity identification and management options between grades <2 or ≥2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46 nontrainees) were included. For patients with grades <2 versus ≥2 HE, a higher percentage of respondents were better at correctly diagnosing grades ≥2 compared with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was checked significantly more often in grades <2, whereas more aggressive investigation for precipitating factors was ordered in HE grades >2. Serum ammonia levels were ordered in almost a third of grade ≥2 patients. For trainees and nontrainees, HE grades were identified similarly between groups. Trainees were less likely to order serum ammonia and low-protein diets, more likely to order rifaximin, and more likely to perform a more thorough workup for precipitating factors compared with nontrainee respondents. There was excellent concordance in the classification of grade ≥2 HE between nontrainees versus trainees, but lower grades showed discordance. Important differences were seen regarding blood ammonia, specialized testing, and nutritional management between trainees and nontrainees. These results have important implications at the patient level, interpreting multicenter clinical trials, and in the education of practitioners. Liver Transplantation 24 587-594 2018 AASLD.

A prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis.

The diagnosis of alcoholic hepatitis (AH) often requires a transjugular liver biopsy (TJLB), a procedure that is not always readily accessible. We analyzed plasma biomarkers to estimate the presence of histological features of AH among patients with clinical suspicion of AH. Using enzyme-linked immunosorbent assay, we tested M65 and M30 (circulating fragments of cytokeratin-18) and their respective fraction carried by microvesicles (MVs), CCL20 and TREM1. Leukocyte, platelet, and endothelial-derived MVs were quantified by way of flow cytometry. Test and validation cohorts prospectively included patients with clinical features of AH undergoing TJLB. In the test cohort, 46 of 83 (55%) patients showed histological features of AH. Age, bilirubin, INR, and creatinine (ABIC) score was B or C in 83%. Patients with histologically proven AH had higher levels of total and MV-bound M65 and total and MV-bound M30 and CCL20 than those without (P < 0.001 for all tests). Levels of TREM-1 and of subpopulations of MVs were not different between groups. M65 and M30 both had an area under the receiver operating characteristics curve of 0.84 to estimate the presence of AH. For M65, a cutoff of 2000 IU/L had a positive predictive value of 91%, whereas a cutoff of 641 IU/L had a negative predictive value of 88%. In the validation cohort, AH was histologically confirmed in 48 of 68 (71%) patients. ABIC score was B or C in 69% of patients. For M65, the above cutoffs had a diagnostic accuracy of 81%. Even better results were obtained in patients with suspicion of severe AH (ABIC B or C) in both cohorts. CONCLUSION: Plasma levels of cytokeratin-18 fragments are reliable noninvasive markers of AH. Using the proposed cutoffs for M65, two thirds of TJLB can be avoided, which can be useful in centers where this technique is not readily available. (Hepatology 2017;66:555-563).

Role of the transjugular intrahepatic portosystemic shunt in the management of severe complications of portal hypertension in idiopathic noncirrhotic portal hypertension.

UNLABELLED: Idiopathic noncirrhotic portal hypertension is a heterogeneous group of diseases characterized by portal hypertension in the absence of cirrhosis. The efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in this population are unknown. The charts of patients with idiopathic noncirrhotic portal hypertension undergoing TIPS in seven centers between 2000 and 2014 were retrospectively reviewed. Forty-one patients were included. Indications for TIPS were recurrent variceal bleeding (n = 25) and refractory ascites (n = 16). Patients were categorized according to the presence (n = 27) or absence (n = 14) of significant extrahepatic comorbidities. Associated conditions were hematologic, prothrombotic, neoplastic, immune, and exposure to toxins. During follow-up (mean 27 ± 29 months), variceal rebleeding occurred in 7/25 (28%), including three with early thrombosis of the stent. Post-TIPS overt hepatic encephalopathy was present in 14 patients (34%). Eleven patients died, five due the liver disease or complications of the procedure and six because of the associated comorbidities. The procedure was complicated by hemoperitoneum in four patients (10%), which was fatal in one case. Serum creatinine (P = 0.005), ascites as indication for TIPS (P = 0.04), and the presence of significant comorbidities (P = 0.01) at the time of the procedure were associated with death. Mortality was higher in patients with significant comorbidities and creatinine ≥100 µmol/L (P < 0.001). CONCLUSION: In patients with idiopathic noncirrhotic portal hypertension who have normal kidney function or do not have severe extrahepatic conditions, TIPS is an excellent option to treat severe complications of portal hypertension. (Hepatology 2016;64:224-231).

[Idiopathic non-cirrhotic portal hypertension: An update]. / Hypertension portale non cirrhotique idiopathique : indications et conduite pratique du traitement.

Idiopathic non-cirrhotic portal hypertension is an under-estimated cause of portal hypertension. The diagnosis requires the exclusion of cirrhosis, common causes of chronic liver disease and venous obstruction of the portal and hepatic veins. It has been associated with various extra-hepatic conditions that are most frequently immunologic, prothrombotic, hematologic and toxic. The most frequent clinical complications are variceal hemorrhage and portal vein thrombosis. Complications of portal hypertension should be managed as in patients with cirrhosis.

Pregnancy and vascular liver disease.

Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd-Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation.

The transjugular intrahepatic portosystemic shunt in the treatment of portal hypertension: current status.

The transjugular intrahepatic portosystemic shunt (TIPS) represents a major advance in the treatment of complications of portal hypertension. Technical improvements and increased experience over the past 24 years led to improved clinical results and a better definition of the indications for TIPS. Randomized clinical trials indicate that the TIPS procedure is not a first-line therapy for variceal bleeding, but can be used when medical treatment fails, both in the acute situation or to prevent variceal rebleeding. The role of TIPS to treat refractory ascites is probably more justified to improve the quality of life rather than to improve survival, except for patients with preserved liver function. It can be helpful for hepatic hydrothorax and can reverse hepatorenal syndrome in selected cases. It is a good treatment for Budd Chiari syndrome uncontrollable by medical treatment. Careful selection of patients is mandatory before TIPS, and clinical followup is essential to detect and treat complications that may result from TIPS stenosis (which can be prevented by using covered stents) and chronic encephalopathy (which may in severe cases justify reduction or occlusion of the shunt). A multidisciplinary approach, including the resources for liver transplantation, is always required to treat these patients.

Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension.

BACKGROUND AND AIM: To evaluate hepatic hemodynamics in patients with nodular regenerative hyperplasia of the liver (NRH) with portal hypertension (PHT). METHODS: We retrospectively reviewed the charts of 24 patients referred for PHT related to biopsy-proven NRH. Hemodynamic measurements included wedged hepatic vein (WHVP) and inferior vena cava (IVCP), and, in 12 patients, portal vein pressure (PVP). Hepatic vein pressure gradient (HVPG: WHVP-IVCP) and portal vein pressure gradient (PVPG: PVP-IVCP) were calculated. RESULTS: Nodular regenerative hyperplasia was associated in 24 patients with various diseases (oxaliplatin chemotherapy, treatment with purine antagonists, post liver transplantation, hematologic and rheumatologic conditions and HIV infection). Liver function parameters were either completely normal or slightly impaired. Patients were referred for gastroesophageal varices (n = 18), and/or ascites (n = 11), and/or splenomegaly (n = 20). In patients with varices or ascites, HVPG was lower than 10 mmHg (a cut-off point for the presence of varices and/or ascites) in 15/21, suggesting a pre-sinusoidal component to their PHT confirmed by a PVP higher than 12 mmHg in 12/12 patients. The mean difference between HVPG and PVPG was 8.7 mmHg in these patients. Ten patients were treated by transjugular intrahepatic portosystemic shunt. None of them re-bled, and one presented transient hepatic encephalopathy. CONCLUSIONS: Presinusoidal PHT associated with NRH is probably related to compression of portal venules by the regenerative nodules. In patients with HTP and a HVPG < 10 mmHg, the diagnosis of NRH must be suspected and PVP measured, which is important in the management of these patients.

Usefulness of endoscopic ultrasonography in hepatology.

Endoscopic ultrasonography (EUS) is used to evaluate patients with hepatobiliary diseases. The technique is useful for the diagnosis of esogastric varices in selected cases of portal hypertension, and to evaluate the pathogenic role and prognostic value of the collateral circulation in patients with this condition. When coupled with the Doppler technique, EUS can be used to guide injection sclerotherapy and to verify the obliteration of varices (particularly fundal varices) after endoscopic treatment. Hemodynamic changes induced in the collateral circulation by vasoactive drugs can also be measured with Doppler-EUS. Fine-needle aspiration under EUS guidance is useful in the diagnosis of focal liver lesions and perihepatic adenopathy, and in the evaluation of biliary tract diseases. New indications can be developed in the future after adequate experimental validation.