#466 Cirrhosis Update with Scott Matherly

January 13, 2025 | By Elena Gibson

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Update your approach to cirrhosis evaluation and management with Dr. Scott Matherly Associate Professor of Hepatology and Gastroenterology at Virginia Commonwealth University 

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Show Segments

• Intro, disclaimer, guest bio
• Case from Kashlak; Definitions
• Cirrhosis Diagnosis and Initial Evaluation 
• Cirrhosis Physical Examination 
• Decompensated Cirrhosis Management 
• Ascites and TIPS
• MELD and transplant consideration
• Outro

Cirrhosis Update Pearls

1. Ask about alcohol use, family history and metabolic comorbidities when taking a history to determine the etiology of cirrhosis.
2. An ALT >25 IU/l for females and >33 IU/l for males is abnormal
3. FIB-4 score can be calculated to evaluate the risk of advanced fibrosis based on labs
4. Decompensation is the development of clinically evident portal hypertension including overt ascites, variceal bleeding and overt hepatic encephalopathy. 
5. The median survival of patients drops significantly following decompensation from 12 years to 1.5 to 2 years.
6. Carvedilol is the preferred beta blocker for management of esophageal varices and portal hypertension. 
7. Patients with an original MELD >18 have a higher risk of mortality and liver failure following a TIPS.
8. Clinically relevant portal hypertension is typically seen when the hepatic venous pressure gradient is greater than 10.
9. A MELD score >15 is a critical threshold where the benefits of liver transplantation outweigh the risks of waiting. Individuals with liver decompensation or MELD >15 should be referred for transplant evaluation.

Cirrhosis Update Notes

Check out our prior episodes on Cirrhosis with Dr. Matherly #100:Cirrhosis Initial Evaluation and Management and #101 Cirrhosis: Medications, Decompensation and Complications. Additional episodes for review of cirrhosis management include #142 Cirrhosis TIPS for Acute Complications and #227 Baffled by NAFLD 

Initial Evaluation

History

Ask about alcohol use, family history and metabolic comorbidities. Patients with a history of Roux-en-Y bypass are at increased risk of alcohol related liver damage due to increased alcohol level peaks in the bloodstream after intake due to lack of first pass gastric metabolism. 

Physical Exam 

Dr. Matherly does a full physical exam, starting with the hands and look for the seven hand findings of cirrhosis (see infographic from Episode #100) which include: Terry’s nails, palmar erythema, dupuytren’s contracture, clubbing, spider angiomas. 

Labs

Initial lab workup should include

1. CMP, CBC, PT/INR 
2. Viral: hepatitis C Ab, hepatitis B sAg, hepatitis B sAb, hepatitis B cAb
3. Genetic: Alpha 1 antitrypsin level, ferritin/TSAT (hemochromatosis), consider ceruloplasmin in the correct clinical context 
4. Autoimmune: ANA, anti smooth muscle antibody, IgG immunoglobulin level, AMA 

Remember that an ALT >25 IU/l for individuals born female and >33 IU/l for individuals born male is abnormal (Kwo 2016).Thrombocytopenia is an important marker to consider the likelihood of advanced fibrosis. 

FIB-4

Calculate the FIB-4 to help evaluate the likelihood of advanced fibrosis based on labs. FIB-4 <1.45 for viral hepatitis and <1.3 for steatotic liver disease is associated with F0-F1 fibrosis. A low score can be reassuring against the presence of advanced fibrosis, and a higher score should prompt further evaluation (Duarte-Rojo 2024). 

Imaging 

Review the imaging to look for evidence of cirrhosis and portal hypertension including enlargement of portal vein or splenomegaly (though splenomegaly may have other etiologies, particularly without portal vein enlargement). 

Next Steps 

Consider further evaluation for fibrosis in patients with an elevated FIB-4 or in patients with conflicting data such as imaging with signs of portal hypertension/cirrhosis but labs that do not suggest this. Further evaluation of the presence of fibrosis can be evaluated in multiple ways.

1. Vibration controlled transient elastography 
2. Magnetic resonance elastography 
3. Liver biopsy

Management of Decompensation

Decompensation is the development of clinically evident portal hypertension including overt ascites, variceal bleeding and overt hepatic encephalopathy. Defining decompensated vs. compensated cirrhosis is clinically significant because outcomes change. The median survival for compensated cirrhosis is 12 years, and the median survival of decompensated cirrhosis is approximately 2 years (D’Amico 2006, Tandon 2021). Dr. Matherly describes considering patients “clinically recompensated” when they previously had clinical evidence of portal hypertension but have not in many years, which may occur from dramatic improvements to the causative agent like curing HCV or alcohol cessation. 

Varices 

Dr. Matherly typically recommends a baseline EGD to evaluate for cirrhosis in patients with cirrhosis. The Baveno VI Consensus notes EGD can be avoided in those with platelets > 150k and shear-wave elastography demonstrating liver stiffness < 20 kPa; risk of varices is < 5% and these markers should be checked annually (Franchis 2015). Regarding varices seen on CT imaging, these can be paraesophageal and not necessarily increase intraluminal risk. Management of varices has evolved with increased evidence that carvedilol is the preferred non-selective beta-blocker (NSBB). The recent AASLD guidelines recommend the use of carvedilol in portal hypertension (AASLD Kaplan 2023). Carvedilol is recommended as the preferred NSBB as studies have shown improvement in lowering portal pressures compared to propranolol due to carvedilol’s anti-alpha-adrenergic activity (AASLD Kaplan 2023, Sinagra 2014). PREDESCI trial showed decreased frequency of decompensation with use of carvedilol (PREDESCI 2019). Start with carvedilol 6.25mg daily, and Dr. Matherly titrates up to 12.25 twice daily if the systolic blood pressure remains > 90 mmHg. 

Ascites 

Ascites is a poor prognostic indicator. Management of ascites includes: 

1. Monitoring sodium intake. Dr. Matherly finds the 2 gram restriction may restrict caloric intake and put individuals at risk for sarcopenia, so he educates and empowers individuals to notice their salt intake and its effects on fluid retention
2. Diuretics: typically start at 40mg of furosemide and 100mg of spironolactone, maintaining a ratio of 20mg furosemide: 50mg spironolactone (Biggins 2021)
3. Transjugular intrahepatic portosystemic shunt (TIPS) consideration 

Spontaneous bacterial peritonitis (SBP) is a complication of ascites with significant morbidity and mortality. Ensure completion of an early diagnostic paracentesis if SBP is on the differential or if a patient with ascites is hospitalized. 

Hepatic Encephalopathy 

Hepatic encephalopathy (HE) is a clinical diagnosis. HE is more than just elevated ammonia- it is a complex interplay between shunting around the liver, liver dysfunction and sarcopenia. In general, muscle metabolizes a significant amount of ammonia and as patient’s lose muscle mass they become more prone to HE. Dr. Matherly advises against using an ammonia level to clinically track HE, but describes how it can be useful at low levels.

Treatment of HE includes aiming for 3 to 4 bowel movements a day. This can be achieved with a combination of lactulose or polyethylene glycol as tolerated. Rifaximin is also used as an adjunct for management of HE (Khalessi 2024). 

Transjugular intrahepatic portosystemic shunt (TIPS)

The liver collects 25% of your cardiac output. As the liver becomes fibrotic, blood has a hard time flowing through it leading to elevated pressures in the portal vein and complications of portal hypertension. A TIPS allows the blood flow to bypass the liver through a low pressure stent front the portal vein to the hepatic vein. A TIPS immediately decreases portal pressures and reduces ascites and varices. However, the risk of hepatic encephalopathy does increase following TIPS (30-50% of people) (Nardelli 2024). In addition to considering the risk of HE with a TIPS procedure, patients with an original MELD >18 have a higher risk of mortality and liver failure following a TIPS (Biggins 2021, Ferral 2004). 

Portal Hypertension Measurement

Portal hypertension can be measured based on the transjugular hepatic venous pressure gradient (HVPG). The HVPG is typically measured as part of a transjugular liver biopsy and during a TIPS procedure. HVPG is measured by subtracting the wedge pressure  in the hepatic vein (wedged hepatic venous pressure [WHVP]) from the measured pressure in the hepatic vein (free hepatic venous pressure [FHVP]). 

HVPG = WHVP – FHVP     

Normal <5 mmHg, >5 mmHg portal hypertension, >10 mmHg clinically significant portal hypertension (Garcia-Tsao 2017)

Four Ways Cirrhosis can Kill you 

1. Liver failure: The way to prevent this is to identify the etiology of liver disease and treat it. For example avoiding alcohol or treating hepatitis C. 
2. Bleeding: variceal hemorrhage  
3. Liver cancer: HCC surveillance every 6 months with an ultrasound and AFP (AASLD 2023 guidelines). Dr Matherly considers additional imaging, like CT or MR, when the quality is suboptimal or dense echotexture (Schoenberger 2023).
4. Malnutrition and Sarcopenia – Dr. Matherly recommends patients drink a protein or nutritional shake if they eat less than half of a full size meal for any reason. He also recommends patients eat a snack prior to sleeping at night such as apples with peanut butter. Providers should limit NPO periods when inpatient when possible. 

Medication Use with Cirrhosis 

Acetaminophen can be used safely in patients with cirrhosis at a maximum daily dose of 2g/day.  Acetaminophen is the preferred analgesic compared to NSAIDs due to the risk of NSAID related side effects (Ma 2024). Statins are safe in patients with compensated cirrhosis and provide substantial benefit in patients with cirrhosis, particularly those with MASLD (Kanwal 2023). In patients with decompensated cirrhosis, statin use requires close monitoring as the risk of statin-induced myopathy increases (American Diabetes Care 2024, Munoz 2021). 

MELD Scores 

The original MELD score was created to predict mortality following a TIPS procedure, but it was identified as a good predictor of 90 day mortality of liver disease. There have been many variations of the MELD score. The most recent is the MELD 3.0 which includes biologic sex aiming to improve the scoring system (Kim 2021). This essentially provides one point for being female sex at birth (given their liver disease may be relatively underestimated due to generally lower creatinine levels) in hopes of providing more equitable transplant allocation. 

Considering Transplant 

Dr. Matherly encourages providers to refer patients for a transplant evaluation at the time of clinical decompensation or when the MELD score is >15. A liver transplant offers a survival benefit for patients with a MELD score >15 (Aberg 2015, Luo 2018). 

Links

1. Episode 100 Cirrhosis Initial Evaluation and Management
2. Episode 101 Medications,decompensation and complications

Goal

Listeners will develop a framework to approach the initial evaluation and management of cirrhosis.  

Learning objectives

After listening to this episode listeners will…  

1. Identify the initial steps to evaluate the etiology of cirrhosis 
2. Describe the clinical findings of decompensation in patients with cirrhosis 
3. Define screening and management recommendations for esophageal varices in patients with cirrhosis 
4. Determine which patients may benefit from evaluation of TIPS for ascites and esophageal varices management
5. Define HCC screening recommendations for patients with cirrhosis 

Disclosures

Dr. Matherly reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Gibson EG, Matherly S, Williams PN, Watto MF. “#466 Cirrhosis Update with Scott Matherly”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast January 13, 2025.