摘要
Individualized care for portal hypertension: Not quite yetJournal of HepatologyVol. 63Issue 3PreviewA consensus on management of portal hypertension was lacking prior to 1990, and perhaps not surprisingly, results reported on response to interventions were quite heterogenous. The Baveno meetings presented structured protocols for the management of the acute variceal bleeding episode and a consensus on both primary and secondary prophylaxis. What is evident with the passage of time from the first Baveno workshop (1990) to Baveno VI (2015), the subject of this editorial [1], is the significant impact the adoption of these consensus documents has had on bleeding related mortality, greater than 30–40% in the early 1980s to 7–12% in recent times [2,3] (Fig. Full-Text PDF Points to be considered when using transient elastography for diagnosis of portal hypertension according to the Baveno’s VI consensusJournal of HepatologyVol. 63Issue 4PreviewWe read with great interest the consensus that was recently published by de Franchis et al. on behalf of the Baveno VI Faculty [1]. The use of transient elastography (TE) for clinical stratification of cirrhotic patients for portal hypertension was one of the main points discussed on the last workshop. According to the Baveno’s VI consensus; (i) TE values higher than 15 kPa could be used for diagnosis of compensated advanced chronic liver disease (cACLD); (ii) liver stiffness by TE ⩾20–25 kPa could be sufficient to rule-in clinically significant portal hypertension (CSPH); and (iii) TE <20 kPa associated with platelet count >150,000 could safely avoid screening of oesophageal varices by endoscopy. Full-Text PDF Reply to “Points to be considered when using transient elastography for diagnosis of portal hypertension according to the Baveno’s VI consensus”Journal of HepatologyVol. 63Issue 4PreviewOne of the main new topics in the recent Baveno VI Consensus workshop was the use of non-invasive methods (mainly transient elastography, TE) for the screening and surveillance of gastroesophageal varices and portal hypertension in patients with chronic liver disease (CLD) [1]. In that sense, during the workshop essentially three main aspects were outlined by the panelists: 1) the ability of TE to permit the early detection of patients with CLD at risk of developing/having severe fibrosis and portal hypertension and as a consequence of this, the proposal of the new definition of compensated advanced CLD (cACLD); 2) the possibility of classifying patients (rule-in) with virus-related cACLD as having clinically significant portal hypertension (CSPH) with the sole information of TE measurement; and 3) the identification of patients with cACLD in whom screening endoscopy could be safely avoided (rule-out) using TE measurement and platelet count. Full-Text PDF Portal hypertension is the haemodynamic abnormality associated with the most severe complications of cirrhosis, including ascites, hepatic encephalopathy and bleeding from gastroesophageal varices. Variceal bleeding is a medical emergency associated with a mortality that, in spite of recent progress, is still in the order of 10–20% at 6 weeks. The evaluation of diagnostic tools and the design and conduct of good clinical trials for the treatment of portal hypertension have always been difficult. Awareness of these difficulties has led to the organisation of a series of consensus meetings. The first one was organised by Andrew Burroughs in Groningen, the Netherlands in 1986 [[1]Methodology and review of clinical trials in portal hypertension. Excerpta Medical Congress Service N° 763. Oxford, Amsterdam, New York1987Google Scholar]. After Groningen, other meetings followed, in Baveno, Italy in 1990 (Baveno I) [[2]de Franchis R. Pascal J.P. Ancona E. Burroughs A.K. Henderson J.M. Fleig W. et al.Definitions, methodology and therapeutic strategies in portal hypertension. A consensus development workshop.J Hepatol. 1992; 15: 256-261Abstract Full Text PDF PubMed Scopus (164) Google Scholar], and in 1995 (Baveno II) [3de Franchis R. Developing consensus in portal hypertension.J Hepatol. 1996; 25: 390-394Abstract Full Text PDF PubMed Scopus (121) Google Scholar, 4de Franchis R. Portal Hypertension II. Proceedings of the second Baveno international consensus workshop on definitions, methodology and therapeutic strategies. Blackwell Science, Oxford1996Google Scholar], in Milan, Italy in 1992 [[5]Spina G.P. Arcidiacono R. Bosch J. Pagliaro L. Burroughs A.K. Santambrogio R. et al.Gastric endoscopic features in portal hypertension: final report of a consensus conference.J Hepatol. 1994; 21: 461-467Abstract Full Text PDF PubMed Scopus (104) Google Scholar], in Reston, U.S.A. [[6]Grace N.D. Groszmann R.J. Garcia-Tsao G. Burroughs A.K. Pagliaro L. Makuch R.W. et al.Portal hypertension and variceal bleeding: an AASLD single topic symposium.Hepatology. 1998; 28: 868-880Crossref PubMed Scopus (331) Google Scholar] in 1996, in Stresa, Italy, in 2000 (Baveno III) [7de Franchis R. Updating consensus in portal hypertension: report of the Baveno III consensus workshop on definitions, methodology and therapeutic strategies in portal hypertension.J Hepatol. 2000; 33: 846-852Abstract Full Text Full Text PDF PubMed Scopus (488) Google Scholar, 8de Franchis R. Portal Hypertension III. Proceedings of the IIIrd Baveno International Consensus Workshop on Definitions, Methodology and Therapeutic Strategies. Blackwell Science, Oxford, UK2001Crossref Google Scholar], again in Baveno in 2005 (Baveno IV) [9de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension.J Hepatol. 2005; 43: 167-176Abstract Full Text Full Text PDF PubMed Scopus (944) Google Scholar, 10de Franchis R. Portal Hypertension IV. Proceedings of the IVth Baveno international consensus workshop on methodology of diagnosis and treatment. Blackwell Publishing, Oxford, UK2006Google Scholar], in Atlanta in 2007 [[11]Garcia-Tsao G. Bosch J. Groszmann R. Portal hypertension and variceal bleeding, unresolved issues. Summary of an American Association for the study of liver disease and of the European Association for the Study of the Liver single-topic conference.Hepatology. 2008; 47: 1764-1772Crossref PubMed Scopus (188) Google Scholar], and again in Stresa in 2010 (Baveno V) [12de Franchis R. on behalf of the Baveno V FacultyReport of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension.J Hepatol. 2010; 53: 762-768Abstract Full Text Full Text PDF PubMed Scopus (1116) Google Scholar, 13de Franchis R. Portal Hypertension V. Proceedings of the Vth Baveno international consensus workshop. Wiley-Blackwell, Oxford, UK2011Crossref Google Scholar]. The aims of these meetings were to develop definitions of key events in portal hypertension and variceal bleeding, to review the existing evidence on the natural history, the diagnosis and the therapeutic modalities of portal hypertension, and to issue evidence-based recommendations for the conduct of clinical trials and the management of patients. All these meetings were successful and produced consensus statements on some important points, although several issues remained unsettled. To continue the work of the previous meetings, a Baveno VI workshop was held on April 10–11, 2015. The workshop was attended by many of the experts responsible for most of the major achievements of the last years in this field. Many of them had attended the previous meetings as well. A concept that has gained wide acceptance over the past few years is the fact that patients in different stages of cirrhosis have different risks of developing complications and of dying. Accordingly, the Baveno VI workshop was entitled “Stratifying risk and individualizing care for portal hypertension”. The main fields of discussion were the use of invasive and non-invasive methods for the screening and surveillance of gastroesophageal varices and of portal hypertension, the impact of aetiological therapy for cirrhosis, the primary prevention of decompensation, the management of the acute bleeding episode, the prevention of recurrent haemorrhage and other decompensating events, and vascular diseases of the liver in cirrhotic and non-cirrhotic patients. For each of these topics, a series of consensus statements were discussed and agreed upon. Whenever applicable, the level of existing evidence was evaluated and the recommendations were ranked according to the Oxford System [[14]Available from .Google Scholar] (i.e., level of evidence from 1 = highest to 5 = lowest; grade of recommendation from A = strongest, to D = weakest). The presentations given during the workshop are reported ‘in extenso’ in the Baveno VI proceedings [[15]de Franchis R, Editor. Portal Hypertension VI. Proceedings of the VIth Baveno international consensus workshop. New York, USA: Springer, in press.Google Scholar]. A summary of the most important conclusions is reported here. Whenever relevant, the changes from previous consensus statements are outlined. The areas where major new recommendations were made are: screening and surveillance, the importance of obesity, comorbidities and malnutrition, the use of beta blockers in patients with refractory ascites/end-stage liver disease, and anticoagulation and portal vein thrombosis in liver cirrhosis. •Six-week mortality should be the primary endpoint for studies for treatment of acute variceal bleeding (5;D).•5 day treatment failure is defined using Baveno IV/V criteria without ABRI (adjusted blood requirement index) and with a clear definition of hypovolemic shock (1b;A).•Baveno IV/V criteria correlate with 6-week mortality (1b;A) and should be included in future studies as a secondary endpoint to allow further validation (5;D).•Additional endpoints should be reported including: need for salvage therapy (tamponade, additional endoscopic therapy, transjugular intrahepatic portosystemic shunt [TIPS], surgery etc.); blood transfusion requirements and days of ICU/hospital stay (5;D). •The introduction of transient elastography (TE) in clinical practice has allowed the early identification of patients with chronic liver disease (CLD) at risk of developing clinically significant portal hypertension (CSPH) (1b;A).•For these patients, the alternative term “compensated advanced chronic liver disease (cACLD)” has been proposed to better reflect that the spectrum of severe fibrosis and cirrhosis is a continuum in asymptomatic patients, and that distinguishing between the two is often not possible on clinical grounds (5;D).•Currently, both terms: “cACLD” and “compensated cirrhosis” are acceptable (5;D).•Patients with suspicion of cACLD should be referred to a liver disease specialist for confirmation, follow-up and treatment (5;D). •Liver stiffness by TE is sufficient to suspect cACLD in asymptomatic subjects with known causes of CLD (1b;A).•TE often has false positive results; hence two measurements on different days are recommended in fasting conditions (5;D).•TE values <10 kPa in the absence of other known clinical signs rule out cACLD; values between 10 and 15 kPa are suggestive of cACLD but need further test for confirmation; values >15 kPa are highly suggestive of cACLD (1b;A). •Invasive methods are employed in referral centres in a stepwise approach when the diagnosis is in doubt or as confirmatory tests•Methods and findings that confirm the diagnosis of cACLD are:-Liver biopsy showing severe fibrosis or established cirrhosis (1a;A).-Collagen proportionate area (CPA) measurement on histology provides quantitative data on the amount of fibrosis and holds prognostic value (2b;B) and its assessment is recommended (5;D).-Upper GI endoscopy showing gastroesophageal varices (1b;A).-Hepatic venous pressure gradient (HVPG) measurement; values >5 mmHg indicate sinusoidal portal hypertension (1b;A). •HVPG measurement is the gold-standard method to assess the presence of CSPH, which is defined as HVPG ⩾10 mmHg (1b;A).•By definition, patients without CSPH have no gastroesophageal varices, and have a low five year risk of developing them (1b;A).•In patients with virus related cACLD non-invasive methods are sufficient to rule-in CSPH, defining the group of patients at risk of having endoscopic signs of PH. The following can be used (2b;B):-Liver stiffness by TE (⩾20–25 kPa; at least two measurements on different days in fasting condition; caution should be paid to flares of ALT; refer to EASL guidelines for correct interpretation criteria), alone or combined to platelets and spleen size.•The diagnostic value of TE for CSPH in other aetiologies remains to be ascertained (5;D).•Imaging showing collateral circulation is sufficient to rule-in CSPH in patients with cACLD of all aetiologies (2b;B). •Patients with a liver stiffness <20 kPa and with a platelet count >150,000 have a very low risk of having varices requiring treatment, and can avoid screening endoscopy (1b;A).•These patients can be followed up by yearly repetition of TE and platelet count (5;D).•If liver stiffness increases or platelet count declines, these patients should undergo screening esophagogastroduodenoscopy (5;D). •In compensated patients with no varices at screening endoscopy and with ongoing liver injury (e.g. active drinking in alcoholics, lack of SVR in HCV), surveillance endoscopy should be repeated at 2 year intervals (5;D).•In compensated patients with small varices and with ongoing liver injury (e.g. active drinking in alcoholics, lack of SVR in HCV), surveillance endoscopy should be repeated at one year intervals (5;D).•In compensated patients with no varices at screening endoscopy in whom the aetiological factor has been removed (e.g. achievement of SVR in HCV; long-lasting abstinence in alcoholics) and who have no co-factors (e.g. obesity), surveillance endoscopy should be repeated at three year intervals (5;D).•In compensated patients with small varices at screening endoscopy in whom the aetiological factor has been removed (e.g. achievement of SVR in HCV; long-lasting abstinence in alcoholics) and who have no co-factors (e.g. obesity), surveillance endoscopy should be repeated at two year intervals (5;D). •Whatever policy and method is adopted for screening and surveillance, cost should be taken into account in future studies (5;D). •Future studies should explore the possibility to stop surveillance after two controls showing no varices.•Long-term data are needed concerning the benefits of screening and surveillance programs. •Management of patients with cirrhosis should focus on preventing the advent of all complications while in the compensated phase (1b;A).•Due to different prognosis, patients with compensated cirrhosis should be divided in those with and without CSPH (1b;A). The goal of treatment in the first is to prevent CSPH while in the second is to prevent decompensation.•The concept of CSPH is HVPG-driven and cannot completely be substituted at present by non-invasive tools (1b;A).•Aetiological treatment of the underlying liver disease may reduce portal hypertension and prevents complications in patients with established cirrhosis (1b;A) (unchanged).•HVPG change is an acceptable surrogate of clinical outcome in patients with non-cholestatic cirrhosis (2b;B). An HVPG change of 10% or more is to be considered significant (1b;A).•Obesity worsens the natural history of compensated cirrhosis of all aetiologies (1b;A). A lifestyle modification with diet and exercise decreases body weight and HVPG in cirrhosis with obesity (2b;B).•Alcohol abstinence should be encouraged in all patients with cirrhosis irrespective of aetiology (2b;B).•The clinical use of statins is promising and should be evaluated in further phase III studies (1b;A). •Studies should focus on tools, either invasive (e.g. quantitative fibrosis assessment with CPA) and/or preferably non-invasive (e.g. elastography, biomarkers, or combinations or other means), to predict/select patients at risk of decompensation in liver diseases of different aetiology.•Anti-fibrotic strategies and approaches to target, amongst others, the coagulation system, FXR-pathway, renin-angiotensin system, angiogenesis and the gut-liver axis, should be further explored for prevention of decompensation in patients with cirrhosis and CSPH. •Successful cure of the etiologic agent in CLD may improve both liver structure and function, and this could translate into a portal pressure reduction (1b;A). •Comorbidities (obesity, diabetes, cancer, osteoporosis, pulmonary, renal and cardiovascular diseases) are frequently present in patients with compensated cirrhosis. Some of them can contribute to decompensation, while others are a consequence of liver disease (2b;B).•Malnutrition and sarcopenia have been shown to have an impact on hepatic encephalopathy, development of ascites, incidence of infections and survival in cirrhotic patients (1b;A). As the evidence was mainly reported in decompensated patients further studies are needed to draw definitive conclusions on this topic also in patients with compensated cirrhosis (5;D). •There is no indication, at this time, to use beta blockers to prevent the formation of varices (1b;A).•Patients with small varices with red wale marks or Child-Pugh C class have an increased risk of bleeding (1b;A) and should be treated with non-selective beta blockers (NSBB) (5;D).•Patients with small varices without signs of increased risk may be treated with NSBB to prevent bleeding (1b;A). Further studies are required to confirm their benefit. •Either NSBB or endoscopic band ligation is recommended for the prevention of the first variceal bleeding of medium or large varices (1a;A).•The choice of treatment should be based on local resources and expertise, patient preference and characteristics, contraindications and adverse events (5;D). •Traditional NSBB (propranolol, nadolol) (1a;A) and carvedilol (1b;A) are valid first line treatments.•Carvedilol is more effective than traditional NSBB in reducing HVPG (1a;A) but has not been adequately compared head-to-head to traditional NSBB in clinical trials. •Although a single study suggested that cyanoacrylate injection is more effective than beta blockers in preventing first bleeding in patients with large gastroesophageal varices type 2 or isolated gastric varices type 1 (1b;A), further studies are needed to evaluate the risk/benefit ratio of using cyanoacrylate in this setting before a recommendation can be made (5;D). •The decision to treat with beta blockers should be taken when indicated, independent of the possibility of measuring HVPG (1a,A).•HVPG measurement provides prognostic information (1b,A).•HVPG change is a relevant surrogate outcome (1b;A).•Measurement of HVPG response to therapy offers additional relevant information: a decrease in HVPG of at least 10% from baseline or to ⩽12 mmHg after chronic treatment with NSBB is clinically relevant in the setting of primary prophylaxis (1b;A). Similarly, acute HVPG response to intravenous propranolol may be used to identify responders to beta blockers, specifically a decrease in HVPG of 10% or to ⩽12 mmHg may be relevant in this setting (1b;A).•HVPG response to NSBBs is associated with a significant reduction in risk of variceal bleeding (1a;A) and decompensation (1b;A).•HVPG measurements should be encouraged in clinical trials investigating novel therapies, but are not essential if portal hypertension-associated endpoints are well defined (5;D). •The safety of NSBB in subgroups with end-stage disease (refractory ascites and/or spontaneous bacterial peritonitis) has been questioned (2b;B).•NSBB contraindications may be absent when the therapy is firstly prescribed but need to be monitored during the evolution of the disease (5;D).•Close monitoring is necessary in patients with refractory ascites, and reduction of dose or discontinuation can be considered in those who develop low blood pressure and impairment in renal function (4;C).•If NSBB are stopped endoscopic band ligation should be performed (5;D). •More data are needed to unravel the course of disease after cure of the aetiological factor.•Successful treatment of the underlying liver disease (alcohol abstinence, antiviral therapy) may reduce HVPG, size of varices and risk of bleeding. Novel antivirals are expected to expand this knowledge and reinforce data to suggest changes in surveillance intervals of varices and other complications.•Competing risks from comorbidities should be taken into account in future studies.•Future studies are required to describe the impact of early detection and treatment of comorbidities.•The impact of treatments to improve nutritional status on prognosis and mortality should be evaluated.•New prospective studies to assess the safety of NSBB in end-stage disease are warranted. •The goal of resuscitation is to preserve tissue perfusion. Volume restitution should be initiated to restore and maintain hemodynamic stability.•Packed red blood cells transfusion should be done conservatively at a target haemoglobin level between 7 and 8 g/dl, although transfusion policy in individual patients should also consider other factors such as cardiovascular disorders, age, hemodynamic status and ongoing bleeding (1b;A).•Recommendations regarding management of coagulopathy and thrombocytopenia cannot be made on the basis of currently available data (5;D).•PT/INR is not a reliable indicator of the coagulation status in patients with cirrhosis (1b;A). •Antibiotic prophylaxis is an integral part of therapy for patients with cirrhosis presenting with upper gastrointestinal (GI) bleeding and should be instituted from admission (1a;A).•The risk of bacterial infection and mortality are very low in patients with Child-Pugh A cirrhosis (2b;B), but more prospective studies are needed to assess whether antibiotic prophylaxis can be avoided in this subgroup of patients.•Individual patient risk characteristics and local antimicrobial susceptibility patterns must be considered when determining appropriate first line acute variceal haemorrhage antimicrobial prophylaxis at each centre (5;D).•Intravenous ceftriaxone 1 g/24 h should be considered in patients with advanced cirrhosis (1b;A), in hospital settings with high prevalence of quinolone-resistant bacterial infections and in patients on previous quinolone prophylaxis (5;D). •Recent studies suggest that either lactulose or rifaximin may prevent hepatic encephalopathy in patients with cirrhosis and upper GI bleeding (1b;A). However, further studies are needed to evaluate the risk/benefit ratio and to identify high risk patients before a formal recommendation can be made (5;D).•Although, there are no specific studies in acute variceal bleeding, it is recommended to adopt the recent EASL/AASLD HE guidelines which state that episodic HE should be treated with lactulose (25 ml q 12 h until 2–3 soft bowel movements are produced, followed by dose titration to maintain 2–3 soft bowel movements per day) (5;D). •Child-Pugh class C, the updated MELD score, and failure to achieve primary haemostasis are the variables most consistently found to predict six week mortality (2b;B). •In suspected variceal bleeding, vasoactive drugs should be started as soon as possible, before endoscopy (1b;A).•Vasoactive drugs (terlipressin, somatostatin, octreotide) should be used in combination with endoscopic therapy and continued for up to five days (1a;A).•Hyponatremia has been described in patients under terlipressin, especially in patients with preserved liver function. Therefore, sodium levels must be monitored (1b;A). •Following hemodynamic resuscitation, patients with upper GI bleeding and features suggesting cirrhosis should undergo esophagogastroduodenoscopy within 12 h of presentation (5;D).•In the absence of contraindications (QT prolongation), pre-endoscopy infusion of erythromycin (250 mg IV 30–120 min before endoscopy) should be considered (1b;A).•The availability both of an on-call GI endoscopist proficient in endoscopic haemostasis and on-call support staff with technical expertise in the usage of endoscopic devices enables performance of endoscopy on a 24/7 basis and is recommended (5;D).•Patients with acute variceal haemorrhage should be considered for ICU or other well monitored units (5;D).•In patients with altered consciousness, endoscopy should be performed with protection of the airway (5;D).•Ligation is the recommended form of endoscopic therapy for acute oesophageal variceal bleeding (1b;A).•Endoscopic therapy with tissue adhesive (e.g. N-butyl-cyanoacrylate) is recommended for acute bleeding from isolated gastric varices (IGV) (1b;A) and those gastroesophageal varices type 2 (GOV2) that extend beyond the cardia (5;D).•To prevent rebleeding from gastric varices, consideration should be given to additional glue injection (after two to four weeks), beta-blocker treatment or both combined or TIPS (5;D). More data in this area are needed.•EVL or tissue adhesive can be used in bleeding from gastroesophageal varices type 1 (GOV1) (5;D). •An early TIPS with PTFE-covered stents within 72 h (ideally <24 h) must be considered in patients bleeding from EV, GOV1 and GOV2 at high risk of treatment failure (e.g. Child-Pugh class C <14 points or Child-Pugh class B with active bleeding) after initial pharmacological and endoscopic therapy (1b;A). Criteria for high risk patients should be refined. •Balloon tamponade, given the high incidence of its severe adverse events, should only be used in refractory oesophageal bleeding, as a temporary “bridge” (for a maximum of 24 h) with intensive care monitoring and considering intubation, until definitive treatment can be instituted (5;D). •Data suggest that self-expanding covered oesophageal metal stents may be as efficacious and a safer option than balloon tamponade in refractory oesophageal variceal bleeding (4;C). •Persistent bleeding despite combined pharmacological and endoscopic therapy is best managed by PTFE-covered TIPS (2b;B).•Rebleeding during the first five days may be managed by a second attempt at endoscopic therapy. If rebleeding is severe, PTFE-covered TIPS is likely the best option (2b;B). •Trials of preventative strategies in acute kidney injury in variceal bleeding should be undertaken.•Treatment and prevention of HE.•Optimal use of glue obliteration in gastric variceal bleeding.•Role of endoscopic ultrasound in variceal injection therapy.•Alternative endoscopic haemostasis techniques in EVB, e.g., haemostatic powders.•Improve prognostic models: Better stratification of risk to determine applicability of updated MELD or other potential new models to improve stratification of risk to determine type of treatment.•Applicability of models to determine other issues such as timing of the initial endoscopy, duration of the drug therapy and type of treatment.•Use of early TIPS in gastric varices.•Use of balloon occluded retrograde transvenous obliteration (BRTO) in IGV. •First line therapy for all patients is the combination of NSBB (propranolol or nadolol) + EVL (1a;A).•EVL should not be used as monotherapy unless there is intolerance/ contraindications to NSBB (1a;A).•NSBB should be used as monotherapy in patients with cirrhosis who are unable or unwilling to be treated with EVL (1a;A).•Covered TIPS is the treatment of choice in patients that fail first line therapy (NSBB + EVL) (2b;B).•Because carvedilol has not been compared to current standard of care, its use cannot be recommended in the prevention of rebleeding (5;D). •In patients with cirrhosis and refractory ascites [[16]Moore K. Wong F. Gines P. Bernardi M. Ochs A. Salerno F. et al.The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club.Hepatology. 2003; 38: 258-266Crossref PubMed Scopus (695) Google Scholar] NSBB (propranolol, nadolol) should be used cautiously with close monitoring of blood pressure, serum sodium and serum creatinine (4;C).•Until randomized trials are available NSBB should be reduced/discontinued if a patient with refractory ascites develops any of the following events (5;D):-Systolic blood pressure <90 mmHg-Hyponatremia (<130 mEq/L)-Acute kidney injury [[17]Angeli P. Wong F. Ginés P. Bernardi M. Boyer T.D. Gerbes A. et al.Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites.J Hepatol. 2015; 62: 968-974Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar]•[This assumes that drugs that could precipitate these events (e.g. NSAIDs, diuretics) have been removed].•The consequences of discontinuing NSBB in the setting of secondary prophylaxis are unknown.•If there was a clear precipitant for these events (e.g. spontaneous bacterial peritonitis, haemorrhage), reinitiation of NSBB should be considered after these abnormal parameters return to baseline values after resolution of the precipitant (5;D).•If reinitiating NSBBs, dose should be re-titrated, starting at the lowest dose (5;D)•If the patient continues to be intolerant to NSBB and is an appropriate TIPS candidate, covered TIPS placement may be considered (5;D). •PHG has to be distinguished from gastric antral vascular ectasia because treatments are different (4;C).•NSBB are first line therapy in preventing recurrent bleeding from PHG (1b;A).•TIPS might be considered in patients with transfusion-dependent PHG in whom NSBB and/or endoscopic therapies fail (4;C). •Primary endpoints in patients after variceal haemorrhage depend on the p