Cirrhosis. Take control of cirrhosis and treat your patients like the pros! In this episode of The Curbsiders, Dr. Scott Matherly, assistant professor in the Dept of Medicine at Virginia Commonwealth University and board certified hepatologist, builds upon his introduction to cirrhosis. You already know what to look out for and how to diagnose these patients, now it’s time to build your knowledge and medical repertoire against this deadly condition! Topics include: high protein diet, ascites, diuretics, hepatic encephalopathy, lactulose vs rifaximin, portal hypertension, esophageal varices, beta blockers, spontaneous bacterial peritonitis prophylaxis and more pathophysiology!
Written by: Cyrus Askin MD
Infographics: Beth Garbitelli
Produced by: Cyrus Askin MD and Matthew Watto MD
Hosts: Cyrus Askin MD, Matthew Watto MD, Stuart Brigham MD, Paul Williams MD
Guest: Scott Matherly MD
In NASH interventions such as Vitamin E, Pioglitazone and Liraglutide all seem to have some evidence suggesting they may help prevent or even reverse cirrhosis (PIVENS Trial, Pioglitazone in NASH, LEAN Trial ).
Lifestyle modifications, such as high protein diets and sodium restriction (under 2000 mg daily)can be useful in managing cirrhotic patients when utilized appropriately.
The cirrhotic condition is characterized by parenchymal liver disease and portal hypertension. It is generally the sequelae of portal hypertension to which most therapies are targeted. -Dr Matherly
Treatment of ascites: Spironolactone can be used as monotherapy (PMID 12873814) or in combination with furosemide in ratio of 100 mg spironolactone to 40 mg furosemide. Furosemide monotherapy is more likely to cause hypokalemia (PMID 7035545)
Hepatic encephalopathy (HE): Most feared complication by patients due to unpredictability and amnestic effects. Tell patients to self titrate lactulose to three bowel movements daily. Mechanism of action remains controversial. -Dr Matherly
Treatment of HE: Lactulose and/or rifaximin for hepatic encephalopathy, non-selective beta-blockers for varices, and medications like midodrine, and octreotide for hepatorenal syndrome.
Dr. Matherly: Spontaneous bacterial peritonitis (SBP) antibiotic prophylaxis is not for everyone.
Secondary prophylaxis is strongly recommended. -Dr Matherly
Cautiously consider primary prophylaxis in patients with risk-factors for infection, especially in the era of C. difficile and antibiotic resistance -Dr Matherly
Mortality: In the decompensated cirrhotic with ascites, around 45% of all-comers will live 5 years from the time of decompensation. (PMID 24128415)
In-depth Show Notes
What may delay the progression of NASH to cirrhosis?
Vitamin E – PIVENS trial showed evidence of reversing NASH on biopsy, but this trial excluded diabetics and cirrhotics! PIVENS Trial (Wiki JC Link)
Do not put on low protein diet regardless of recurrent hepatic encephalopathy
Think of Cirrhosis as a disease process with “two separate but connected problems” – Dr. Matherly
Hepatic Parenchymal Disease – High MELD, elevated bilirubin, INR and eventually hepatocellular carcinoma. Impaired synthetic function (protein, clotting factors, etc.)
Portal Hypertension: elevated blood pressure in the portal vein which drains the gut
Pathophysiology and complications
Ascites – Increased pressure in hepatic sinusoids (capillaries of liver) leads to increased fluid/hydrostatic pressure and decreased oncotic pressure (low albumin) leads to fluid spilling out into liver parenchyma which then weeps into the peritoneal cavity.
Hepatic encephalopathy (HE) – a clinical diagnosis with signs including: slow to answer questions, repetitive speech, reversal of sleep-wake cycle
Dr. Matherly recommends: Step 1 = 40 mg furosemide + 100 mg of spironolactone daily because this ratio seems to maintain normokalemia. This dosing seems to be dogmatic, but effective based on this 1981 study (Fogel MR et al. J Clin Gastroenterol. 1981 PMID: 7035545 PMID ) so we keep doing it!
Doses can be advanced in increments that maintain 40:100 mg ratio as needed to counteract the kidneys’ sodium avidity and maintain potassium homeostasis.
Spironolactone: sexual side effects and gynecomastia are a big deal in men, may consider alternative agents (such as eplerenone, but cost is an issue)
Hepatic Encephalopathy – start therapy at the first signs of HE
Lactulose:first line; nonabsorbable disaccharide
Don’t really know how this works, but it does!
Dr. Matherly: Take this medication, change the dose whenever you need to, to have 3 bowel movements daily
Side effects: bloating, nausea, abdominal discomfort
550 mg twice daily is well tolerated but very expensive
Varices and Beta-Blockers
Beta blockers (BB) seem to be beneficial in cirrhotic patients, to a point when used for variceal prophylaxis in patients with large varices or prior variceal bleed. Must use non-selective BB because beta-1 activity reduces cardiac output while the beta-2 activity will lead to unopposed alpha activity and resultant vasoconstriction of the splanchnic vasculature to reduce portal inflow / pressure.
Discontinue BB in acute kidney injury, systolic BP under 90 mmHg, Na under 120 meq/L (Dr. Matherly / Baveno VI)
Midodrine & Octreotide are reserved for type 1 hepatorenal syndrome
Midodrine monotherapy: Can use to temporarily increase blood pressure / renal perfusion in ascitic patients who are refractory to diuretics, but this is controversial / not a standard use. -Dr Matherly’s expert opinion
Who needs prophylaxis for Spontaneous Bacterial Peritonitis (SBP)?
A patient with history of SBP must be on prophylaxis
In a patient who has never had SBP be much more selective regarding primary prophylaxis. Usually for low-protein ascites + kidney disease or hospitalized / at risk for infection. – Dr. Matherly
Goal: In contrast to Dr. Matherly’s first episode which focused on introducing cirrhosis, this episode will equip listeners with the tools to manage cirrhosis like a pro! You will learn about the pathophysiology of cirrhosis and the “separate but connected” problems that every cirrhotic will face. Most importantly, in this episode Dr. Matherly take us on a tour of the medications that comprise our armamentarium against cirrhosis and describes when they are best used.
After listening to this episode listeners will…
Recognize early interventions in the NASH patient which may help prevent or delay the progression to cirrhosis
Appreciate what lifestyle recommendations there are for cirrhotic patients
Appreciate the significance of carrying the diagnosis of “decompensated cirrhotic”
Understand the two “separate but connected” problems that lead to the symptoms of cirrhosis and the pathophysiology behind theses problems
Know how to medically address the common disease processes in a cirrhotic patient with an understanding of the different therapeutic interventions available to the primary care provider
Disclosures: Dr. Matherly reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
01:30 Guest bio
02:28 NASH, diet, vitamin E, pioglitazone and prevention of cirrhosis
06:56 Clinical case of decompensated cirrhosis
09:02 Pathophysiology of circulatory dysfunction in cirrhosis and use of diuretics
18:25 Hepatic encephalopathy, ammonia, lactulose and rifaximin
25:10 Timing of medical therapy
26:39 MAP of 82 mmHg, beta blockers and variceal bleeding