December Liver Briefs

B Wildman-Tobriner et al. Gastoenterol 2018; 155: 1428-35.  This retrospective study which pooled data from 3 phase 2a trials with 370 subjects with nonalcoholic fatty liver disease (NAFLD) found that MRI iwth proton density fat fraction (PDFF) “did not accurately identify patients with NAS ≥4 (AUROC – 0.72) or fibrosis stage ≥3 (AUROC =0.66).”  Thus, this study indicates that currently liver histology remains the gold standard to determine severity of liver damage in paitents with NAFLD.

Related blog posts

P Nahon et al. Gastroenterol 2018; 155: 1436-1450. This study looks closer at whether direct-acting antivirals (DAA) for hepatitis C could increase the risk of hepatocellular carcinoma (HCC) in patients (n=1270) with cirrhosis. The authors found that the crude 3-year cumulative incidence of HCC were 5.9% in the DAA and 3.1% in the SVR-IFN group. However, after Cox analysis, “we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89).”  The authors indicated that patient characteristics (age, diabetes, reduced liver function) and lower screening intensity were the reasons for the increased crude rates of HCC.

Related blog post: Liver Short Takes December 2017

Love this sign –it indicates the truth of the saying:  ‘common sense is not that common’ (attributed to Voltaire)

Briefly Noted: Progression of Fatty Liver Disease on MRI

M Mouzaki  et al. J Pediatr 2018; 201: 86-92. This study with 65 patients evaluated nonalcoholic fatty liver disease (NAFLD) progression between two MRI studies, with a median time span of 27 months.

Key findings:

  • There was no correlation between change in liver stiffness and change in ALT; there was a weak correlation between ALT change and fat fraction.
  • MRI fat fraction and stiffness decreased in 29% and 20% of patients respectively and increase in 25% and 22% respectively.

My take: When we find effective therapies, we will need better non-invasive markers to follow NAFLD progression.

Related blog posts

Tea House Trail, near Lake Louise, Banff

Why Shopping for Health Care Does Not Work and What Can Be Done About That

From NY Times:  Shopping for Health Care Simply Doesn’t Work. So What Might? (Thanks to Ben Enav for pointing out this article)

An excerpt:

What this latest study suggests, in the context of other studies, is that if people can’t shop for elective M.R.I.s, there’s hardly a chance they are going to do so with other health care procedures that are more complicated and variable.

Even if 40 percent of health care is shoppable, people are not shopping. What seems likelier to work is doing more to influence what doctors advise.

For example, we could provide physicians with price, quality and distance information for the services they recommend. Further, with financial bonuses, we could give physicians (instead of, or in addition to, patients) some incentive to identify and suggest lower-cost care.

Leaving decisions to patients, and making them spend more of their own money, doesn’t work.

Assessment of Organ Donation –MRI Often Precludes Need for a Liver Biopsy

A recent retrospective single-center study (J Satkunasingham et al. Liver Transplantation 2018; 24: 470-77) shows that MRI is a good tool to assess hepatic steatosis.  In total there were 144 liver donor candidates; a subset of 32 underwent liver biopsy.

When examining magnetic resonance spectroscopy (MRS) and MRI -proton pump density fat fraction (PDFF), the authors found that MRS-PDFF and MRI-PDFF had 95% and 100% negative predictive value in identifying patients with clinically  significant histologic steatosis (≥10%).

The associated editorial by James Trotter (pg 457-58) makes several important points:

  • Currently living donor transplantation in the U.S. accounts for 4% of all transplants
  • In his center (and most centers), protocol biopsy are not required prior to liver donation.  The main indications for donor liver biopsy are biochemical dysfunction or steatosis on imaging studies.

My take (borrowed from editorial): “Noninvasive estimation of hepatic steatosis is sufficiently accurate to forgo liver biopsy in most donors, although ultimately this decision will continue to rest with the individual center.”


Liver Articles -Spring 2018

C Sikavi et al. Hepatology 2018; 67: 847-57.  This systematic review highlights that the combination of hepatitis C virus (HCV) infection and HIV infection is no longer a difficult-to-treat population with the implementation of direct-acting antivirals (DAAs). There are similar sustained virologic responses (SVRs) among those with and those without HIV.  In clinical trials, patients with combined HCV-HIV had SVRs of 93.5-98% with DAA treatment; “real-world cohorts” had SVRs of 90.9%-98%.

MS Middleton et al. Hepatology 2018; 67: 858-72.  Using data from the prospective CyNCh trial (cysteamine for NAFLD), the authors examined MRIs for diagnostic accuracy among 169 enrolled children.  In this group, 110 (65%) and 83 (49%) had MRI and liver biopsy at baseline. MRI-PDFF (proton density fat fraction) was able to classify grade 1 steatosis from grade 2-3 steatosis with area under receiving operator characteristic curve of 0.87.  Thus, this study shows MRI-estimated PDFF has high diagnostic accuracy.

G Mieli-Vergani et al. JPGN 2018; 66: 345-60.  Position paper for Pediatric Autoimmune Liver Disease (AIH, ASC, de novo AIH after liver transplantation). This is a very useful review.  A couple of pointers from the authors:

  • “Present experience with budesonide as the first-line treatment is limited and does not appear to offer clear clinical advantage over the standard treatment”[prednisone]
  • Fecal calprotectin should be obtained to evaluate for IBD in patients with autoimmune liver disease, “even in asymptomatic children.”

JM Cotter et al. JPGN 2018; 66: 227-33. This retrospective study with 39 patients with primary sclerosing cholangitis (PSC) showed a lack of correlation between liver tests and fibrosis at presentation.  Average age of PSC diagnosis was 11.2 years, 74% had inflammatory bowel disease and 51% had autoimmune hepatitis. Related blog post: Big Pediatric PSC Study (with 781 children)

When Will MRI Obviate the Need for a Liver Biopsy in Pediatric NAFLD?

A recent study (JB Schwimmer et al. Hepatology 2015; 1887-95, editorial Vos MB, pages 1779-80) examines the accuracy of magnetic resonance imaging (MRI) compared with liver histology in children with nonalcoholic fatty liver disease.

This prospective validation study enrolled 174 children with a mean age of 14 years.  The MRI estimated the liver proton density fat fraction (PDFF).

Key findings:

  • Liver MRI-PDFF correlated with steatosis grade; the correlation was particularly strong at high and low end values.  Thus, a very low MRI-PDFF was highly likely to predict a steatosis grade 0 or 1 while a very high value corresponded to high steatosis levels.
  • Liver MRI-PDFF was weaker in children with stage 2-4 fibrosis than in children with no fibrosis

The editorial notes that this study “is one of hundreds now published in the literature on MRI and NAFLD…The superiority of MR-based methods…over ultrasound is clear.  The question is why are we still ordering abdominal ultrasounds to diagnose NAFLD in children?”  The barriers for usage of MRI include cost, potential sedation, and nonuniform methods for MRI usage.

The paper conclude that “MRI is not yet sufficient to replace liver biopsy in children.”  The editorial also indicates that the MRI era is fast approaching but not viable today.

Take-home point: Due to the huge numbers of patients with pediatric NAFLD, MRI remains a terrific area for research but remains problematic in clinical practice.  Given the expense of MRI, until its use can reduce liver biopsies or improve management, its role is likely to remain limited.

Turner Field

Turner Field


Improving MRI for NAFLD

From MedicalNewsToday – a summary of a recent Hepatology study by Jeffrey B. Schwimmer, MD and colleagues.

Excerpts from along with image.

In this study, the researchers compared a new MRI technique to the standard liver biopsy method of assessing fat in the liver. To do this, the team enrolled 174 children who were having liver biopsies for clinical care. For each patient, the team performed both MRI-estimated PDFF and compared the results to the standard pathology method of measuring fat on a liver biopsy.

Screenshot from MedicalNews

Screenshot from MedicalNewsToday

The team found a strong correlation between the amount of liver fat as measured by the new MRI technique and the grade of liver fat determined by pathology. This is an important step towards being able to use this technology for patients. Notably, the correlation was influenced by both the patient’s gender and the amount of scar tissue in the liver. The correlation between the two techniques was strongest in females and in children with minimal scar tissue.

Depending on how the new MRI technology is used, it could correctly classify between 65 and 90 percent of children as having or not having fatty liver tissue.”

“… However, further refinements will be needed before this or any other MRI technique can be used to diagnose NAFLD in an individual child.

What Happens with Cost Transparency in Medicine?

While it is true that some tests, like MRI and CT scans, may be performed better (better images, better contrast administration, etc) at some locations than others, many times the test is similar but the costs to the patient may be widely divergent.  Yet, for most patients the exact costs are not known until the bill arrives in the mail.  A recent study shows that many patients will consider the costs of these expensive tests if they are provided beforehand.  Here’s the NY Times link, MRI study,  and an excerpt:

study released Monday in the journal Health Affairs suggests we are smarter than that.

The insurer WellPoint provided members who had scheduled an appointment for an elective magnetic resonance imaging test with a list of other scanners in their area that could do the test at a lower price. The alternative providers had been vetted for quality, and patients were asked if they wanted help rescheduling the test somewhere that delivered “better value.”

Fifteen percent of patients agreed to change their test to a cheaper center. “We shined a light on costs,” said Dr. Sam Nussbaum, WellPoint’s chief medical officer. “We acted as a concierge and engaged consumers giving them information about cost and quality.”

The program resulted in a $220 cost reduction (18.7 percent) per test over the course of two years, said Andrea DeVries, the director of payer and provider research at HealthCore, a subsidiary of WellPoint, which conducted the study. It compared the costs of scanning people in the WellPoint program with those of people in plans that did not offer such services.

Related blog posts:

Imaging in NAFLD -Don’t Rely on Ultrasound

A recent article (Clin Gastroenterol Hepatol 2014; 12: 765-73) notes that ultrasound is not accurate for diagnosing NAFLD:

The link to the article:, video abstract: (from Jeff Schwimmer’s twitter feed) ,and an excerpt from the article’s abstract:


We analyzed 9 studies comprising 610 children; 4 studies assessed ultrasonography and 5 studies assessed magnetic resonance imaging (MRI). Ultrasonography was used in the diagnosis of fatty liver with positive predictive values of 47% to 62%. There was not a consistent relationship between ultrasound steatosis score and the reference measurement of hepatic steatosis. Liver fat as measurements by MRI or by spectroscopy varied with the methodologies used. Liver fat measurements by MRI correlated with results from histologic analyses, but sample size did not allow for an assessment of diagnostic accuracy.


Available evidence does not support the use of ultrasonography for the diagnosis or grading of fatty liver in children. Although MRI is a promising approach, the data are insufficient to make evidence-based recommendations regarding its use in children for the assessment of hepatic steatosis.

Related blog posts:

More imaging needed?

With new tools at our disposal in diagnosing inflammatory bowel disease, we need to decide how and when to use them.  Potential new modalities include stool inflammatory markers, video capsule endoscopy, CT enterography (CTE), and MR enterography (MRE).  Several studies have shown that the information that these studies yield may change management. The latest of these studies (Inflamm Bowel Dis 2012; 18: 219-25) looked at how the knowledge of CTE effected management and physician confidence with Crohn’s disease.

The authors prospectively assessed 273 patients with established or suspected Crohn’s disease.  In their analysis, 70 patients (48%) of established cases had altered management because of CTE and 69 (54%) of suspected cases.  These changes were considered to be  independent of clinical, serological or histologic findings.  Changes included medication modification in 45 (16.2%), excluding Crohn’s disease in 46 (16.8%), surgery referral in 10 (3.7%), alternate diagnosis established in 9 (3.2%), & canceling surgery in 7 (2.6%).  The authors considered excluding active small disease as an important management plan change; this occurred in 18 patients (6.6%).

The authors state that their current practice is to use MRE for serial imaging rather than CTE, to minimize risks from radiation; though CTE is often the initial imaging.

My take on this article is that information from imaging often increases the certainty about the diagnosis and gives a more complete picture of the severity.  It is likely that more information leads to more aggressive therapy.  At the same time, in pediatric gastroenterology, the trend towards using more effective therapy earlier in the course of the disease has developed even in the absence of extensive imaging (see previous: Only one chance to make first impression).  Whether more imaging in pediatric patients would be worthwhile is not known.

Additional references:

  • -JPGN 2008; 47: 31.  Capsule endoscopy may reclassify pediatric IBD
  • -NEJM 2010; 363: 1, 4. Safety of CT. Can have overdose of radiation and even standard doses could cause complications. Also, a big issue is downstream unnecessary testing due to incidental findings.
  • -Clin Gastro 2008; 6:283. Use of CT enterography.
  • -JPGN 2010; 51: 603.  MRE for suspected IBD.  Useful in Crohn’s disease.
  • -IBD 2004;10: 278-285.  WCE for Crohn’s (review)  Capsule can help differentiate UC from Crohn’s.