Portal Hypertension and Related Complications

Educational Objectives

The goal of this program is to improve the management of portal hypertension and its complications. After hearing and assimilating this program, the clinician will be better able to:

1. Treat patients with cirrhosis, portal hypertension, and ascites.
2. Define acute kidney injury in cirrhosis.

Summary

Cirrhosis: a result of structural fibrotic changes (70%) and vascular issues (30%), eg, vasoconstriction, loss of endothelial nitric oxide synthase, and stellate cell activation; chronic liver disease progresses to compensated cirrhosis to decompensated cirrhosis and beyond; the 2 categories of compensated cirrhosis are mild portal hypertension (pHTN; hepatic venous pressure gradient [HVPG] 5-10 mm Hg) and clinically significant (CS) pHTN (HVPG >10); CSpHTN increases the risk for decompensation and complications, eg, varices, ascites, encephalopathy, bleeding varices, and increasing Model for End-Stage Liver Disease (MELD) score; chronic complications include sarcopenia and hepatorenal syndrome (HRS); noninvasive tools can diagnose CSpHTN (eg, FibroScan stiffness 20-25 with platelet count <150,000/μL, stiffness >25, or portosystemic collateral circulation on imaging)

Clinically significant pHTN: the key driver of decompensation in cirrhosis; initial mild pHTN leads to splanchnic vasodilation and increased blood flow, which progresses to CSpHTN; this triggers varices, neurohumoral activation, sodium and water retention, increased flow, and worsened pHTN; neurohumoral activation contributes to the 30% of pHTN that is reversible and treatable; eventual complications include ascites, variceal hemorrhage, and portosystemic shunting that causes encephalopathy; because CSpHTN drives decompensation but mild pHTN does not, treatment for mild pHTN focuses on eliminating or treating the etiology; in CSpHTN, the focus is on preventing decompensation by lowering portal pressure; antifibrotics, weight loss, alcohol cessation, and treating autoimmune hepatitis and hepatitis B and C improve fibrosis

β-blockers: reduce inflow; carvedilol (CAR) is more effective than classic β-blockers (eg, propranolol, natalol) as it blocks α-1 receptors (ie, vasoconstriction) as well as β-1 and β-2 effects; it is first-line therapy but haS more hypotensive effects than other β-blockers; PRESDESCI trial (Villaneuva et al, 2019) showed that β-blockers reduce risk for decompensation (mostly ascites, with some effect on varices) and improve survival; guidelines now support CAR for patients with CSpHTN; for symptomatic patients without access to noninvasive testing, use endoscopic screening; if small varices are present, use CAR (unless contraindicated); for larger or high-risk varices, use CAR or endoscopic ligation; guidelines state that, once β-blockers are initiated, continued surveillance is unnecessary unless new symptoms or bleeding occur

Use of CAR with other therapies: data are lacking for CAR plus other β-blockers in compensated cirrhosis; Tevethia et al (2024) — assessed combination CAR and band ligation for primary prophylaxis in decompensated cirrhosis (ie, Child-Pugh Class B or C) with high-risk varices; combination therapy improved bleeding risk and survival over either modality alone; this is not yet covered in the guidelines

Ascites: driven by the hepatic sinusoids; the peritoneal system can absorb ≤7 L of fluid daily; although it often presents acutely, ascites is a chronic condition; diet, diuretic nonadherence, or use of nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol can provoke acute symptoms; ascites can be characterized using serum and ascitic albumin, ascites total protein, complete blood cell count, and differential to rule out infection; glucose, lactate dehydrogenase, and pH are not necessary; management — start sodium restriction at CSpHTN diagnosis (do not wait for ascites); consider liver transplantation candidacy early, especially for marginalized patients, as ascites increases mortality; implement a high-protein diet (1.5 g/kg body weight) as soon as ascites appears; stop NSAIDs, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs), especially if ascites control is poor and the patient is normotensive; check echocardiography at 3 to 6 mo in patients who require up-titration of diuretics (rule out portopulmonary hypertension or right-sided heart failure)

Transjugular intrahepatic portosystemic shunt (TIPS): important for patients with recurrent ascites who do not yet have refractory ascites; Saab et al (2006) showed patients with recurrent (not refractory) ascites who received TIPS had much better outcomes than those undergoing repeated large-volume paracentesis, with no significant difference in encephalopathy; using controlled expansion stents results in better survival rates and lower encephalopathy risk than older stents that expand over size; TIPS controls the degree of portal-pressure lowering; adverse effects include increased cardiac output, right heart pressure, and risk for encephalopathy; smaller stents are preferred, as they can be dilated over time if needed

Poorly controlled ascites and spontaneous bacterial peritonitis (SBP): maintain a mean arterial pressure (MAP) >65 mm Hg (correlates with systolic blood pressure [BP] >90 mm Hg) during β-blocker use to improve survival; discontinue β-blockers if MAP drops <65 mm Hg to prevent adverse outcomes

Acute kidney injury (AKI): is present in 25% of hospitalized patients with cirrhosis; mortality is high, even if AKI resolves; often functional and linked to infection; ≈50% of patients have hypovolemia, and 25% have HRS-AKI (20% have acute tubular necrosis [ATN]); an overlapping spectrum of pathophysiologic processes affects the liver and kidney; AKI in the setting of cirrhosis — defined as a >50% increase in creatinine from baseline or an increase of >0.3 mg/dL; stage 1 is a 1.5- to 2-fold increase, stage 2 is a 2- to 3-fold increase, and stage 3 is a >3-fold increase, creatinine >4 mg/dL, or renal replacement therapy; pathophysiology of HRS — a progression of the events that cause decompensation; renal vasoconstriction occurs when neurohumoral and cardiac responses are overwhelmed; almost all patients have hypotension, ascites, and hyponatremia, ie, decompensation; β-blockers can modulate immune pathways activated by bacterial translocation; prevent iatrogenic HRS by using infection, SBP, and bleeding prophylaxis, preventing diarrhea from lactulose, providing albumin with large-volume paracentesis, and using caution with diuretics, NSAIDs, ACE inhibitors, ARBs, and contrast

Distinguishing between different types of AKI: prerenal — stop diuretics, hold β-blockers if systolic BP is <90 mm Hg, exclude and treat infection, and administer albumin (≤1 g/kg per day); this should produce a rapid decline in serum creatinine; contrast-induced ATN — features proteinuria, red blood cells, and high urinary neutrophil gelatinase-associated lipocalin (NGAL) levels, with no serum creatinine response to albumin; HRS-AKI — lacks ATN features; fractional excretion and urinary NGAL are low, with no response to albumin

Management: provide prophylaxis for varices, infection, and hepatic encephalopathy; avoid NSAIDs, ACE inhibitors, and ARBs, especially with ascites or low BP; early referral for liver transplantation is encouraged; increase renal perfusion by holding diuretics and β-blockers and providing albumin; if AKI persists, consider vasoconstrictors, eg, terlipressin (TER) or norepinephrine, and albumin (midodrine with octreotide and albumin has a low response rate); TER has a ≈30% response rate in reversing HRS but no change in overall survival; patients with a baseline creatinine <3 mg/dL have a 37% chance of responding (no response with creatinine >5 mg/dL; 28% chance with creatinine 3-5 mg/dL); vasoconstrictors should be used cautiously in patients with ischemic disease or pulmonary edema and not at all in patients with acute-on-chronic liver failure grade 3 or high MELD scores

Algorithm for managing acute AKI in the hospital: when a patient is admitted with elevated creatinine, document AKI and differentiate between prerenal, HRS, and ATN; administer albumin within 4 to 6 hr and reassess creatinine levels at 12 to 14 hr; if there is no response and criteria for HRS-AKI are met, begin treatment with midodrine plus octreotide and albumin; point-of-care ultrasonography is used to assess volume status to adjust treatment accordingly; if patient does not improve ≤48 hr, start TER; renal replacement therapy might be needed if TER is contraindicated; adjust TER based on response

Readings

de Franchis R, Bosch J, Garcia-Tsao G, et al; Baveno VII Faculty. Baveno VII - renewing consensus in portal hypertension [published correction appears in J Hepatol. 2022 Jul;77(1):271. doi: 10.1016/j.jhep.2022.03.024.]. J Hepatol. 2022;76(4):959-974. doi:10.1016/j.jhep.2021.12.022; Du L, Wei N, Maiwall R, et al. Differential diagnosis of ascites: etiologies, ascitic fluid analysis, diagnostic algorithm. Clin Chem Lab Med. 2023;62(7):1266-1276. Published 2023 Dec 20. doi:10.1515/cclm-2023-1112; Ginès P, Krag A, Abraldes JG, et al. Liver cirrhosis. Lancet. 2021;398(10308):1359-1376. doi:10.1016/S0140-6736(21)01374-X; Kellum JA, Romagnani P, Ashuntantang G, et al. Acute kidney injury. Nat Rev Dis Primers. 2021;7(1):52. Published 2021 Jul 15. doi:10.1038/s41572-021-00284-z; Saab S, Nieto JM, Lewis SK, et al. TIPS versus paracentesis for cirrhotic patients with refractory ascites. Cochrane Database Syst Rev. 2006;2006(4):CD004889. Published 2006 Oct 18. doi:10.1002/14651858.CD004889.pub2; Tevethia HV, Pande A, Vijayaraghavan R, et al. Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the ‘CAVARLY TRIAL’. Gut. 2024;73(11):1844-1853. Published 2024 Oct 7. doi:10.1136/gutjnl-2023-331181; Villanueva C, Albillos A, Genescà J, et al.β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial [published correction appears in Lancet. 2019 Jun 22;393(10190):2492. doi: 10.1016/S0140-6736(19)31404-7.]. Lancet. 2019;393(10181):1597-1608. doi:10.1016/S0140-6736(18)31875-0.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Fallon was recorded at the 49th Annual Texas Meeting, held September 20-22, 2024, in Austin, TX, and presented by The Texas Society for Gastroenterology and Endoscopy. For information about upcoming CME activities from this presenter, please visit tsge.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

GE390702

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.