Under certain circumstances, you may need to! Although nonselective beta blockers (NSBBs), such as nadolol and propranolol, have been the cornerstone of medical treatment of portal hypertension in preventing variceal bleeding in patients with cirrhosis for decades, recent reports of their association with worsening survival, increased risk of hepatorenal syndrome and acute kidney injury in patients with refractory ascites or spontaneous bacterial peritonitis [SBP]) 1,2 have added controversy to their routine use in end-stage cirrhosis.
This is because patients with end-stage cirrhosis may be highly dependent on their cardiac output (particularly the heart rate) in maintaining an adequate arterial blood pressure 3-5 and the negative inotropic and chronotropic effects of NSBBs blunt this compensatory mechanism. The result is a drop in the cardiac output that may be particularly significant in the presence of conditions already associated with hypotension, such as sepsis, spontaneous bacterial peritonitis (SBP), or hemorrhage, further increasing the risk of renal hypoperfusion and hepatorenal syndrome.3
Although 2 meta-analysis studies failed to find an association between NSBBs and increased mortality among patients with cirrhosis and ascites, 6,7 serious concerns over the adverse effects of these drugs in at least a subset of patients has not waned. Some have recommended reducing NSBB dose or discontinuing treatment in patients with refractory ascites or SBP and any of the following parameters: 4
- Systolic blood pressure <90 mmHg
- Serum creatinine >1.5 mg/dL
- Hyponatremia <130 mmol/L
Similar recommendations were made by a 2015 consensus conference on individualizing the care of patients with portal hypertension. 8
In the absence of randomized-controlled studies, it seems prudent to proceed with more caution when using NSBBs in patients with end-stage cirrhosis and watch closely for any signs of hypotension or renal function deterioration.
- Serste T, Njimi H, Degre D, et al. The use of beta-lackers is associated with the occurrence of acute kidney injury in severe hepatitis. Liver In 2015;35:1974-82. https://www.ncbi.nlm.nih.gov/pubmed/25611961
- Mandorfer M, Bota S, Schwabl P, et al. Nonselective beta blockers increase risk of hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterol 2014;146:1680-90. https://www.sciencedirect.com/science/article/pii/S0016508514003060?via%3Dihub
- Garcia-Tsao G. The use of nonselective beta blockers for treatment of portal hypertension. Gastroenterol Hepatol 2017;13: 617-19. http://www.gastroenterologyandhepatology.net/archives/october-2017/the-use-of-nonselective-beta-blockers-for-treatment-of-portal-hypertension/
- Reiberger T, Mandorfer M. Beta adrenergic blockade and decompensated cirrhosis. J Hepatol 2017;66: 849-59. https://www.ncbi.nlm.nih.gov/pubmed/27864004
- Giannelli V, Lattanzi, Thalheimer U, et al. Beta-blockers in liver cirrhosis. Ann Gastroenterol 2014;27:20-26. https://www.ncbi.nlm.nih.gov/pubmed/24714633
- Facciorusso A, Roy S, Livadas S, et al. Nonselective beta-blockers do not affect survival in cirrhotic patients with ascites. Digest Dis Sci 2018;63:1737-46. https://link.springer.com/article/10.1007%2Fs10620-018-5092-6
- Njei B, McCarty TR, Garcia-Tsao G. Beta-blockers in patients with cirrhosis and ascites: type of betablocker matters. Gut 206;65:1393-4. https://gut.bmj.com/content/gutjnl/65/8/1393.full.pdf
- De Franchis R. Expanding consensus in portal hypertension. Report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015;63:743-52. https://www.ncbi.nlm.nih.gov/pubmed/26047908
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Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related deaths1. Liver transplant removes the HCC tumor and addresses the underlying cirrhosis. Unfortunately, the demand for liver transplants exceeds the supply of available livers, making it necessary to select patients with the best recurrent-free survival following transplantation. .
Mazzaferro2 found that patients who had one lesion <5 cm, no more than 3 lesions each <3 cm, and no extrahepatic involvement or vascular invasion had significantly higher rates of recurrent-free survival following liver transplant than patients with tumors exceeding this criteria (92% vs 59% at 4 years, respectively, P = .002). This criteria, also known as the Milan criteria, has been substantiated by numerous studies3 and widely adopted. Other more inclusive criteria has also been proposed, including the UCSF criteria4 (one tumor <6.5 cm, no more than 3 tumors, all <4.5 cm and cumulative size <8cm) which have good survival rates, but have not been adopted due to limited supply of available livers.
Interestingly, patients with HCC not initially meeting the Milan criteria but who receive treatment to meet the criteria have similar post-transplantation recurrence-free survival rates as those who meet the criteria without downstaging4,5.
- El–Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007 Jun 30;132(7):2557-76.
- Mazzaferro V, Regalia E, Doci R, et al. L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-699.
- Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence‐based analysis of 15 years of experience. Liver Transplantation 2011;17(S2): S44-S57.
- Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. Liver transplantation. 2002 Sep 1;8(9):765-74.
- Ravaioli M, Grazi GL, Piscaglia F, et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant. 2008;8:2547–2557.
- Yao FY, Kerlan RK, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48:819–827.
Contributed by Marissa Shoji, Medical Student, Harvard Medical School
High serum B12 levels, aka hypercobalaminemia (HC), is not rare among hospitalized patients with 1 study reporting “high” (813-1355 pg/ml) and “very high” (>1355 pg/ml) serum B12 levels in 13 and 7% of patients, respectively1.
Common causes include excess B12 intake, solid neoplasms (particularly, hepatocellular carcinoma and metastatic neoplastic liver disease), blood disorders (eg, myelodysplastic syndrome, CML, and acute leukemias, particularly AML3), and other liver diseases, including alcohol-related diseases as well as acute and chronic hepatitis. Other inflammatory states and renal failure have also been reported2.
Paradoxically, even in the presence of HC, a functional B12 deficiency may still exist. This may be related to poor B12 delivery to cells due to its high binding by transport proteins transcobalamin I and III in HC which may in turn cause a decrease in the binding of B12 to transcobalamin II, a key player in B12 transport to tissues2. In this setting, elevated serum methylmalonic acid and homocysteine levels may be helpful.
- Arendt JFB, Nexo E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. PLoS ONE 2012;9:e45979. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0045979
- Andres E, Serraj K, Zhu J. et al. The pathophysiology of elevated vitamin B12 in clinical practice. Q J Med 2013;106:505-515.https://www.ncbi.nlm.nih.gov/pubmed/23447660