Will Emerging Therapies for Fatty Liver Disease Be Affordable?

With non-alcoholic steatohepatitis (NASH), there are currently no established medical therapies.  However, several candidate medications look promising. However in recent years, many new medications have come with an impressive price tag and this has led to questions about whether emerging therapies for NASH will be affordable.

A recent article looked at the medication Obeticholic Acid, which was approved for treating primary biliary cholangitis.  It is possible that it will be helpful for NASH.  Yet, its cost , currently, is about $70,000 per year

GIHepNews: Despite clinical promise, obeticholic acid may be too expensive for treating NASH

Here’s an excerpt:

In the 72-week Phase II trial, called FLINT, 273 men and women with NASH were randomly assigned to receive OCA or placebo (Lancet 2015;385:956-965). Liver histology improved in 45% of those receiving OCA versus 21% in those receiving sham therapy (P=0.002). An increased risk for pruritus was the most notable adverse event among patients taking OCA (23% vs. 6% for placebo), according to the researchers. Based on the favorable benefit–risk results of the Phase II study, a Phase III trial is ongoing…

The expected benefit of OCA over lifestyle modifications for all the major long-term outcomes, such as decompensated cirrhosis (10% vs. 9.4%), liver-related mortality (9% vs. 8.1%) and transplant-free survival (72.2% vs. 71.5%), were relatively modest, the researchers reported. Those differences resulted in a cost per quality-adjusted life-year saved of $5.2 million with the assumption that 16% of patients would relapse…

 “If the efficacy compared to placebo is of the same order found in the FLINT trial, the current cost of the drug would be prohibitive in a population-based context,” said Dr. Lavine, who was a co-investigator on the trial.

My take: Given the growing burden of NASH, new effective treatments are needed.  In my view, though, cost-effectiveness has to be a consideration.

Prague Castle

NASH: What Helps Beyond Weight Loss?

Full text from ACG article: NASH: What Helps Beyond Weight Loss?

The article reinforces the value of weight loss and exercise for nonalcoholic steatohepatitis (NASH).  It suggests that Vitamin E and/or pioglitazone may be helpful. Many more medications are being evaluated.

My take: As of now, losing weight and exercise remain the cornerstone for NASH treatment.

Distance from Transplant Center -Not a Good Thing for Chronic Liver Disease

It is said that “absence makes the heart grow fonder.”  This expression certainly cannot be extrapolated to the liver.  A recent study (DS Goldberg et al. Clin Gastroenterol Hepatol 2017; 15: 958-60) showed that increased distance to a liver transplant center was associated with higher mortality for patients with chronic liver failure (CLF).

This study examined 16,824 patients with CLF.  In the cohort (879, 5.2%) who lived  >150 miles from the closest LT center there was a 20% higher mortality rate (Hazard ratio of 1.20; P <.001).  According to the authors, mortality with distance “modeled as a continuous variable per unit increase in 50 miles.”

From the discussion:

  • “For patients with CLF, transplant remains the only option for long-term survival. Yet for the 11 out of 12 who are never transplanted, access to specialized care may still prolong life.”
  • Limitations: This study could not account for socioeconomic factors or control for geographical variation in care.  With regard to the later, death rates from liver disease are lowest in New York, where the entire population is within 150 miles of a transplant center.  In contrast, in New Mexico and Wyoming, which have the highest age-adjusted death rates, more than 95% of patients live >150 miles from a transplant center. However, there may be many other differences in care besides distance in these regions.

My take: This study, though with some limitations, bolsters the view that patients with chronic liver disease (and probably other chronic diseases) live longer if in proximity to specialized care.

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Exquisite windows in St. Vitus Cathedral, Prague


Why the Liver is the King of Internal Organs

A nice summary of how great our livers are by the NY Times: The Liver: A ‘Blob’ That Runs the Body

An excerpt:

After all, a healthy liver is the one organ in the adult body that, if chopped down to a fraction of its initial size, will rapidly regenerate and perform as if brand-new. Which is a lucky thing, for the liver’s to-do list is second only to that of the brain and numbers well over 300 items, including systematically reworking the food we eat into usable building blocks for our cells; neutralizing the many potentially harmful substances that we incidentally or deliberately ingest; generating a vast pharmacopoeia of hormones, enzymes, clotting factors and immune molecules; controlling blood chemistry; and really, we’re just getting started.

Defining the Role for Elastography

The ability to determine if a patient has cirrhosis/severe fibrosis with a noninvasive test can help determine appropriate monitoring and treatment for many liver conditions. As such the AGA has provided recommendations for the use of vibration-controlled transient elastography (VCTE).

  • JK Lim et al. Gastroenterol 2017; 152: 1536-43.
  • S Singh et al. Gastroenterol 2017; 152: 1544-77.

Many recommendations are based on the specific unit of measurement, kilopascals (kPa)

Specific recommendations (most with low  or very low quality evidence):

  • “In adults with chronic HCV, we can accurately diagnosis cirrhosis …with VCTE-defined liver stiffness of ≥12.5 (±1) kPa.”  The AGA suggests using VCTE rather than MRE for detection of cirrhosis.
  • “In adults with chronic HCV who have achieved SVR…we can accurately rule out advanced fibrosis (F3 and F4) with post-treatment VCTE-..of ≤9.5 (±1) kPa.” . Even in patients who have had HCV eradicated, if cirrhosis has been identified, careful followup is recommended.
  • “In adults with chronic HBV, we can accurately diagnosis cirrhosis…with VCTE…of ≥11.0 (±1) kPa.”
  • “The AGA makes no recommendation regarding the role of VCTE in the diagnosis of cirrhosis in adults with NAFLD.” For NAFLD, VCTE is not as helpful as with chronic HCV and HBV.  Currently, liver biopsy remains the “gold standard.” However, for noninvasive imaging, “the AGA suggest using MRE, rather than VCTE, for detection of cirrhosis.
  • For adults with suspected compensated cirrhosis, a VCTE of 19.5 or greater can be used “to assess the need for esophagogastroduodenoscopy to identify high risk esophageal varices.”

My take: These elastography recommendations are applicable for adults.  For pediatric patients, these reports suggest that elastography may be helpful in specific circumstances as well.

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Omaha Beach

NAFLD Adult Prospective MRI Study: 42% Prevalence

From Jeff Schwimmer Twitter feed:

Prevalence of Fatty Liver Disease in NE Germany Based on MRI RSNA Radiology, http://dx.doi.org/10.1148/radiol.2017161228

Excerpt from abstract:

From 2008 to 2013, 2561 white participants (1336 women; median age, 52 years; 25th and 75th quartiles, 42 and 62 years) were prospectively recruited to the Study of Health in Pomerania (SHIP). Complex chemical shift–encoded magnetic resonance (MR) examination of the liver was performed, from which PDFF and R2* were assessed…

Prevalence of fatty liver diseases was 42.2% (1082 of 2561 participants); mild, 28.5% (730 participants); moderate, 12.0% (307 participants); high content, 1.8% (45 participants).

Vincent Van Gogh, Portrait de l’artiste, Musee d’ Orsay


Heroin Epidemic Causing Surge in Hepatitis C Infections

From NPR: Heroin Epidemic is Driving a Spike in Hepatitis C Cases

An excerpt:

The number of new Hepatitis C cases leaped nearly 300 percent from 2010 to 2015, according to a report released Thursday by the Centers for Disease Control and Prevention. And the CDC points to the likely culprit behind the spike in cases of the infectious disease: the use of heroin and other injection drugs.

And despite the existence of therapies that can cure more than 90 percent of infections, the organization says the disease remains a deadly threat. In 2013, for instance, the CDC says some 19,000 people died of their infections.

From CNN: New Hepatitis C Infections Triple due to Opioid Epidemic

The number of new nationally reported infections with the virus swelled from 850 in 2010 to 2,436 cases in 2015, with the highest rates among young people, mainly 20- to 29-year-olds, who inject drugs, according to a new report released Thursday by the Centers for Disease Control and Prevention.