Portal hypertension treatment

Portal Hypertension Guidelines: 2016 American Association for the Study of Liver Diseases Guidelines

Measurement

The 2016 AASLD provides the following guidance for noninvasive testing for the diagnosis of clinically significant portal hypertension (CSPH):

• Hepatic venous pressure gradient (HVPG) measurement is the gold-standard method to assess the presence of CSPH, defined as an HVPG of at least 10 mm Hg.
• CSPH can be identified by noninvasive tests: Liver stiffness above 20-25 kPa, alone or combined with platelet count and spleen size. The presence of portosystemic collaterals on imaging studies is sufficient to diagnose CSPH.
• By definition, patients with gastroesophageal varices as demonstrated by endoscopy have CSPH.

Widespread use of the transjugular intrahepatic portosystemic shunt (TIPS) procedure in the 1990s for the management of variceal bleeding led to a resurgence of clinicians' interest in measuring portal pressure. During angiography, a catheter may be placed selectively via either the transjugular or transfemoral route into the hepatic vein. In the healthy patient, free hepatic vein pressure (FHVP) is equal to inferior vena cava pressure. FHVP is used as an internal zero reference point.

Wedged hepatic venous pressure (WHVP) is measured by inflating a balloon at the catheter tip, thus occluding a hepatic vein branch. Measurement of the WHVP provides a close approximation of portal pressure. The WHVP actually is slightly lower than the portal pressure because of some dissipation of pressure in the sinusoidal bed. The WHVP and portal pressure are elevated in patients with sinusoidal portal hypertension, as is observed in cirrhosis.

Gastroesophageal varices

The HVPG is defined as the difference in pressure between the portal vein and the inferior vena cava. Thus, the HVPG is equal to the WHVP value minus the FHVP value (ie, HVPG = WHVP - FHVP). The normal HVPG is 3-6 mm Hg.

Portal hypertension is defined as a sustained elevation of portal pressure above normal. An HVPG of 8 mm Hg is believed to be the threshold above which ascites potentially can develop. An HVPG of 12 mm Hg is the threshold for the potential formation of varices. High portal pressures may predispose patients to an increased risk of variceal hemorrhage.

The AASLD recommends the following for noninvasive testing for the diagnosis of gastroesophageal varices:

• Patients with a liver stiffness below 20 kPa and a platelet count over 150,000/μL have a very low probability (< 5%) of having high-risk varices, and esophagogastroduodenoscopy (EGD) can be circumvented.
• In patients who do not meet these criteria, screening endoscopy for the diagnosis of gastroesophageal varices is recommended when the diagnosis of cirrhosis is made.

Treatment

The 2016 AASLD practice guidelines include, but are not limited to, the treatment recommendations outlined below.

Cirrhosis

For individuals with compensated cirrhosis and mild portal hypertension, the AASLD provides the following guidance:

• The treatment goal is to prevent the development of clinically significant portal hypertension (CSPH)/decompensation and, perhaps, even to achieve regression of cirrhosis.
• Elimination of the etiologic agent is the current mainstay of therapy.
• Drugs that act on portal flow, such as nonselective beta-blockers, will be mostly ineffective in this substage, given that the hyperdynamic circulatory state is not fully developed.

For individuals with compensated cirrhosis and CSPH but without gastroesophageal varices, the AASLD recommends the following:

• The goal of treatment should be to prevent clinical decompensation (ie, it is no longer the objective to prevent varices).
• No evidence exists at present to recommend the use of nonselective beta-blockers to prevent the formation of varices.

In patients with compensated cirrhosis and gastroesophageal varices, AASLD recommendations include the following:

• Nonselective beta-blockers are the recommended therapy for patients with high-risk small esophageal varices (ie, primary prevention in patients with small esophageal varices).
• Either traditional nonselective beta-blockers (eg, propranolol, nadolol), carvedilol, or endoscopic variceal ligation (EVL) is recommended for the prevention of first variceal hemorrhage (VH) (primary prophylaxis) in patients with medium or large varices.
• Treatment selection should be based on patient preference and characteristics.
• Patients on nonselective beta-blockers or carvedilol for primary prophylaxis do not require monitoring with serial esophagogastroduodenoscopy (EGD).
• Not recommended in this setting: The combination therapy of nonselective beta-blockers plus EVL
• Not recommended in the prevention of first VH:Transjugular intrahepatic portosystemic shunt (TIPS) placement

Variceal bleeding

For patients who present with acute esophageal VH, the AASLD guidelines indicate the following:

• Conservative transfusion of packed red blood cell (PRBC): Starting to transfuse when the hemoglobin reaches a threshold of around 7 g/dL, with the goal of maintaining it between 7 and 9 g/dL.
• Short-term (maximum 7 days) antibiotic prophylaxis should be instituted in any patient with cirrhosis and gastrointestinal hemorrhage.
• Intravenous (IV) ceftriaxone 1 g/24 h is the antibiotic of choice and should be used for a maximum of 7 days (consider discontinuing when hemorrhage has resolved and vasoactive drugs discontinued).
• Vasoactive drugs (somatostatin or its analogue, octreotide; vasopressin or its analogue, terlipressin) should be initiated as soon as VH is suspected.
• EGD should be performed within 12 hours of admission and once the patient is hemodynamically stable.
• If a variceal source is confirmed/suspected, EVL should be performed.
• In patients at high risk of failure or rebleeding (Child-Turcotte-Pugh (CTP) class C cirrhosis or CTP class B with active bleeding on endoscopy) who have no contraindications for TIPS, an “early” (preemptive) TIPS within 72 hours from EGD/EVL may benefit selected patients.
• For patients in whom an early TIPS is not performed, IV vasoactive drugs should be continued for 2-5 days and nonselective beta-blockers initiated once vasoactive drugs are discontinued. Rescue TIPS is indicated in these patients if hemorrhage cannot be controlled or if bleeding recurs despite the use of vasoactive drugs plus EVL.
• In patients in whom TIPS is performed successfully, IV vasoactive drugs can be discontinued.

For individuals who have recovered from an episode of acute esophageal VH, the AASLD recommends the following:

• First-line therapy in the prevention of rebleeding: The combination of nonselective beta-blockers plus EVL
• Patients who have had successful placement of a TIPS during the acute episode do not require nonselective beta-blockers or EVL.
• TIPS is the recommended rescue therapy in patients who experience recurrent hemorrhage despite the use of combination therapy nonselective beta-blockers plus EVL.

2017 American Association for the Study of Liver Diseases

The American Association for the Study of Liver Diseases (AASLD) published a practice guideline on portal hypertensive bleeding in cirrhosis in 2017. Key points of the Portal Hypertensive Bleeding in Cirrhosis: Risk Stratification, Diagnosis, and Management: 2016 Practice Guidance by the American Association for the Study of Liver Diseases include the following:

• Patients with a liver stiffness less than 20 kPa and platelet count more than 150,000/mm 3 have a very low probability of having high risk varices and esophagogastroduodenoscopy (EGD) could be circumvented. In patients who do not meet this criteria, screening EGD for gastroesophageal varices (GEV) should be performed once a diagnosis of cirrhosis is made.
• Patients with compensated cirrhosis (CC) without varices on screening endoscopy should have endoscopy repeated every 2 years (with ongoing liver injury or associated conditions, such as obesity and alcohol use) or every 3 years (if liver injury is quiescent, eg, after viral elimination, alcohol abstinence).
• Patients with CC with small varices on screening endoscopy should have endoscopy repeated every year (with ongoing liver injury) or every 2 years (if liver injury is quiescent, eg, after viral elimination, alcohol abstinence).
• Patients with CC without varices or with small varices who develop decompensation should have a repeat endoscopy when this occurs.
• In patients in the earliest stage of CC (patients with mild PH), the objective of treatment is to prevent development of clinically significant portal hypertension (CSPH)/decompensation and perhaps even to achieve regression of cirrhosis.
• Elimination of the etiologic agent is the current mainstay of therapy in the earliest stage of CC.
• Non-selective beta-blockers (NSBBs) will be mostly ineffective in this earliest stage of CC, because the hyper dynamic state is not fully developed.
• In patients with cirrhosis and CSPH but without varices, the objective of treatment should no longer be to prevent varices, but to prevent clinical decompensation.
• There is no evidence at present to recommend the use of NSBBs in preventing formation of varices.
• Traditional NSBBs (propranolol and nadolol), carvedilol, or endoscopic variceal ligation (EVL) is recommended for the prevention of first variceal hemorrhage (VH) (primary prophylaxis) in patients with medium to large varices.
• Choice of treatment should be based on patient preference and characteristics.
• Patients on NSBBs or carvedilol for primary prophylaxis do not require monitoring with serial EGD.
• Combination therapy NSBB plus EVL is not recommended for primary prophylaxis.
• Transjugular intrahepatic portosystemic shunt (TIPS) is not recommended for primary prophylaxis.
• NSBB is the recommended therapy as primary prophylaxis for patients with small varices with high risk features.
• In patients presenting with acute variceal hemorrhage, packed red blood cells (pRBC) transfusion should be done conservatively, starting to transfuse when the hemoglobin reaches a threshold of around 7 g/dL with the goal of maintaining it between 7 and 9 g/dL.
• Short-term (maximum 7 days) antibiotic prophylaxis should be instituted in any patient with cirrhosis and gastrointestinal hemorrhage.
• Intravenous ceftriaxone 1 g/24 h is the antibiotic of choice and should be used for a maximum of 7 days (consider discontinuing when hemorrhage has resolved and vasoactive drugs discontinued).
• Vasoactive drugs (somatostatin or its analogue, octreotide; vasopressin (VP) or its analogue, terlipressin) should be initiated as soon as variceal hemorrhage is suspected.
• EGD should be performed within 12 hours of admission and once the patient is hemodynamically stable.
• If a variceal source is confirmed/suspected, EVL should be performed.
• In patients at high risk of failure or rebleeding (CTP class C cirrhosis or CTP class B with active bleeding on endoscopy) who have no contraindications for TIPS, an "early" (preemptive) TIPS within 72 hours from EGD/EVL may benefit selected patients.
• For patients in whom an early TIPS is not performed, intravenous vasoactive drugs should be continued for 2‐5 days and NSBBs initiated once vasoactive drugs are discontinued. Rescue TIPS is indicated in these patients if hemorrhage cannot be controlled or if bleeding recurs despite vasoactive drugs+EVL.
• In patients in whom TIPS is performed successfully, intravenous vasoactive drugs can be discontinued.
• Combination of NSBB+EVL is first‐line therapy in the prevention of rebleeding in patients who have recovered from an acute episode of VH.
• Patients who have a TIPS placed successfully during the acute episode do not require NSBBs or EVL.
• TIPS is the recommended rescue therapy in patients who experience recurrent hemorrhage despite combination therapy NSBB+EVL.
• For prevention of first VH from gastroesophageal varices type 2 (GOV2) or isolated gastric varices type 1 (IGV1), NSBBs can be used, although the data are not as strong as for EV.
• Prevention of first bleeding from gastroesophageal varices type 1 (GOV1) varices may follow the recommendations for EV.
• Neither TIPS nor balloon retrograde transvenous obliteration (BRTO) are recommended to prevent first hemorrhage in patients with fundal varices that have not bled.
• Patients with acute bleeding from GV should be initially managed in a similar fashion to those bleeding from EV (using a restrictive transfusion policy, vasoactive drug infusion, and antibiotic prophylaxis).
• In patients bleeding from GOV1 varices, either EVL (if technically feasible) or cyanoacrylate glue injection, if available, are the recommended endoscopic treatments.
• TIPS is the treatment of choice in the control of bleeding from cardiofundal varices (GOV2 or IGV1).
• Cyanoacrylate glue injection is an option for cases in which TIPS is not technically feasible.