Category Archives: Hepatology

Can NALFD be improved with bile acid sequestration?

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Probably not (Hepatology 2012; 56: 922-32).

Because bile acid sequestrants like colesevelam (& cholestyramine) lower plasma low density lipoprotein (LDL) levels and can improve glycemic control, a recent study tested the hypothesis that this would result in improvement in patients with biopsy-proven nonalcoholic steatohepatitis (NASH).

Methods: 50 patients were randomly assigned to either colesevelam 3.75 g/d or placebo for 24 weeks.  All patients had a liver biopsy within 6 months as a baseline study.  The primary outcome was liver fat as measured by a MRI technique (proton-density fat-fraction or PDFF) and by MR spectroscopy. At the start and conclusion of the study patients had biochemical assays, MRI-PDFF & MR spectroscopy; also, patients had a liver biopsy at completion of study.

Results: The colesevelam group had increased fat at the conclusion of the study period by a mean difference of 5.6% with PDFF and 4.9% with MR spectroscopy, both compared with placebo group.  In addition, liver biopsy did not detect any effect of treatment.  Looking at the biochemical indices, there was also a trend of increased transaminases in the treatment group compared to the control group (Table 3 in study).

Conclusions: The authors indicate that the increased fat may be due to a compensatory increase in bile acid synthesis.  Also, as the changes in fat were only detected on MRI, future NASH studies may benefit from this technique as well.

Related blog entries:

NAFLD Guidelines 2012 | gutsandgrowth

Pediatric NAFLD Position Paper | gutsandgrowth

Vision and persistence in developing liver transplantation

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A concise perspective article examines the history and challenges of developing liver transplantation into an accepted treatment for end-stage liver disease (NEJM 2012; 367: 1483-86).

Key points:

  • Thomas Starzl 1st attempted liver transplant in 1963.  The 3-year-old boy with biliary atresia did not survive the operation; the next 5 attempts were failures as well with the longest survivor lasting only 23 days.  A moratorium of nearly 4 years was placed after these initial failures.
  • Improvements in immunosuppression were a key advance, including antilymphocyte serum in 1966.  During the 1970s, 70% of liver-allograft recipients died shortly after surgery.
  • Brain death concept, accepted in 1968, allowed for better donor organs (less ischemia)
  • Key immunosuppression advance was in 1979 when Roy Calne (Cambridge) reported the use of cyclosporin for organ transplantation.  Between 1980-81, 70% (n=40) of Starzl’s patients survived more than one year.
  • In 1983, National Institutes of Health at a consensus conference concluded that liver transplantation should be considered a ‘clinically applicable, lifesaving procedure.’
  • Other improvements, such as better organ procurement protocols and preservation along with further improvements in immunosuppression have helped improve 1-year and 5-year survival rates to climb, >85% and >70% respectively in 2010.
  • In 2010, 6291 patients underwent liver transplantation.
  • Remaining challenges include inadequate organ supply, recurrent primary hepatic disease (eg. hepatitis C), adverse drug effects, and post-transplantation complications.

The persistence and vision of Starzl and Calne has been recognized with the Lasker-Debakey Award (Lasker-DeBakey Clinical Medical Research Award – Wikipedia, the …).

How strong is the case for HCC screening?

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Not that strong.  The AASLD guidelines for hepatocellular carcinoma (HCC) have faced additional scrutiny and an editorial reviews the basis for HCC screening recommendations (Hepatology  2012; 56: 793-96).

According to the authors, there have been two randomized controlled trials of HCC screening in China.  One that did not demonstrate benefits of HCC screening relied on resection as the treatment for early-stage HCC.  However, a large proportion of those with screen-detected HCC did not undergo resection.

The second trial demonstrated benefit but had several issues.  First, the statistical analysis has been criticized as faulty due to the cluster randomization method while analyzing with an individual patient basis method.  In addition, most North American cases of HCC are related to HCV rather than HBV; thus, the results may not be applicable.

The editorial counters that there are additional lines of evidence that HCC screening is effective for HCV and that an adequate RCT in this country will never be feasible.  Specifically, they suggest that an adequate study would need 10,000 subjects.  This would be further complicated by informed consent; an Australian study has shown that 90% of patients would refuse randomization and prefer to undergo screening.

The editorial points out that advancement in treatments have lowered the likelihood of morbidity in patients identified through screening as well.

As part of their conclusion, the authors quote Sir Austen Bradford Hill who conducted the first RCT in humans: All scientific work is incomplete…liable to be upset by advancing knowledge.  That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action it appears to demand at a given time.”

Related blog entry:

Looking for trouble | gutsandgrowth

Additional references:

Coming soon –Fibroscan?

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Transient elastography as measured by the Fibroscan device is used throughout the world, except notably in the U.S.  That may change soon as an application is under review by the FDA (Gastroenterology & Hepatology 2012; 8: 605-7).

  • Fibroscan works by measuring shear wave velocity with a 50-MHz wave that is “passed into the liver from a small transducer on the end of an ultrasound probe.”
  • “The technology measures the velocity of the sound wave passing through the liver and then converts that measurement into a liver stiffness measurement.”
  • Takes 5-7 minutes to perform
  • Fibroscan is particularly reliable when showing either no fibrosis or advanced fibrosis.  Less accuracy is noted with moderate fibrosis.
  • Technology can be augmented with noninvasive biomarkers of fibrosis
  • Not reliable in several groups: morbidly obese & patients with ascites

Additional references:

  • Am J Gastroenterol 2011; 106: 2121-22. Staging liver fibrosis for HCV
  • Gastroenterol 2005; 128: 343-50.  Comparison of elastography, biomarkers, and liver biopsy for staging fibrosis