Liver Briefs -October 2019

Briefly noted:

M Mouzaki et al. JPGN 2019; 69: 339-43. In a cohort of 228 patients with 17 (8%) who were receiving psychotropic medications, the use of psychotropic medications was associated with increased nonalcoholic fatty liver disease (NAFLD) severity.  These patients were more likely to be receiving metformin (53% vs 18%) and antihypertensive medications (29% vs 8%).

S Honigbaum et al. JPGN 2019; 69: 344-50. Among 20 infants with biliary atresia, tissue had abundantly expressed lysly oxidase-like 2 (LOXL2) compared to controls.  LOXL2 is an extracellular matrix enzyme that catalyzed cross-linking of collagen and elastin; LOXL2 likely contributes to fibrosis.

Moving Away from Liver Biopsies

A recent review (EB Tapper, AS-F Lok. NEJM 2017; 377: 756-68) provides a good review of liver biopsy and liver imaging. My take of this review is that it highlights the emergence of noninvasive tools (imaging & fibrosis markers) which may supplant liver biopsy.  This article does not delve into how more widespread genetic testing may obviate a liver biopsy in many cases as well. The article notes that about 8% of persons in the U.S. have elevated liver enzymes.

Liver biopsy:

  • “A typical liver biopsy samples one fifty-thousandth of the liver.”
  • Limitations of liver biopsy: sampling error is common, biopsy interpretation is subjective, and biopsies can cause complications.  Pain is noted in 30-50% of patients, serious bleeding in 0.6%, injury to other organs (0.08%), and in rare cases, death (up  to 0.1%).
  • Cost: “the average direct cost of a percutaneous liver biopsy is $1448 (in 2016 U.S. dollars).” Transjugular biopsies are much more expensive.  In addition, there are unmeasured indirect costs, due to missing work.

Some prior blogs on liver biopsy

Blood tests:

  • The article details the formulas for biomarker measurements that predict the risk of fibrosis, inlcuding FIB-4, Lok Index, and NAFLD Fibrosis Score.
  • In most liver diseases, aspartate aminotransferase levels “exceed alanine aminotransferase levels when cirrhosis develops.”
  • Thrombocytopenia “is the earliest indicator of cirrhosis among routine blood tests…[due to] diminished liver function (throbopoietin underproduction) and portal hypertension (splenic sequestration).”
  • Proprietary algorithms to assess fibrosis have variable sensitivity, specificity –include FibroTest (aka FibroSure [LabCorp]), FibroMeter, HepaScore (Quest), FIBROSpect, and the Enhanced Liver Fibrosis Score.

Imaging:

  • Elastography with vibration-controlled transient elastography (VCTE) OR magnetic resonance elastography
  • “Elastography offers excellent negative likelihood ratios for advanced fibrosis but much poorer positive likelihood ratios.”
  • Patients with severe obesity are less likely to obtain adequate study with VCTE and could need magnetic resonance elastography to assess fibrosis.

My take: Noninvasive tests have already sharply reduced the need for liver biopsy.

Related posts:

Magnetic Resonance Elastography in Nonalcoholic Fatty Liver Disease

A recent study (Hepatolology 2014; 60: 1920-8) shows that magnetic resonance (MR) elastography can be an accurate noninvasive tool to assess liver fibrosis.

Background: Assessing severity of liver fibrosis provides important prognostic information in patients with nonalcoholic fatty liver disease (NAFLD); however, these patients are often obese which decreases the success of transient elastography.  In addition, high hepatic fat content may alter the results of transient elastography.  Hence, an alternative noninvasive technique is desirable.

Design: Prospective study with 117 consecutive patients with biopsy-proven NAFLD who also underwent 2D-MR elastography between 2011-2013.

Results:

  • Fibrosis stage: stage 0 n=43, stage 1 n=39, stage 2 n=13, stage 3 n=12, stage 4 n=10.
  • MR elastography identified stage 3-4 with an accuracy of 0.92, with little overlap between advanced (F3-4) and non-advanced (F0-2) values.  The specificity, sensitivity, positive/negative predictive values, and cutoff values are detailed in Table 2.
  • Figure 3 provides a cool picture demonstrating the different MR elastography stiffness heat maps correlated with liver fibrosis. Link to similar web-based image from Siemens.

Bottomline: This technology allows a noninvasive measure of liver fibrosis in NAFLD patients and will probably be of use in other liver conditions.  Given the fact that a liver biopsy is more risky and often expensive, this technology and other noninvasive markers of advanced liver disease will be important tools.

Related blog posts: