Changes in Latitudes and Changes in Autoimmune Liver Disease

GJ Webb et al. Clin Gastroenterol Hepatol 2021; 19: 2587-2596. Open Access: The Epidemiology of UK Autoimmune Liver Disease Varies With Geographic Latitude

Methods: A retrospective cohort study using anonymized UK primary care records (2002-2016). All adults without a baseline diagnosis of AILD (autoimmune liver disease) were included and followed up until the first occurrence of an AILD diagnosis, death, or they left the database.

AIH, autoimmune hepatitis; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis

Key findings:

  • 1314 incident cases of PBC, 396 of PSC, and 1034 of AIH. Crude incidences were as follows: PBC, 2.47 (95% CI, 2.34–2.60); PSC, 0.74 (95% CI, 0.67–0.82); and AIH, 1.94 (95% CI, 1.83–2.06) per 100,000 per year.
  • A more northerly latitude was associated strongly with incidence of PBC: 2.16 to 4.86 from 50°N to 57°N (P = .002) and incidence of AIH: 2.00 to 3.28 (P = .003), but not incidence of PSC: 0.82 to 1.02 (P = .473)
  • After adjustments, PBC was more frequent in smokers than those who had never smoked at 3.40 (3.03–3.77) per 100,000/y and 1.96 (1.80–2.12) cases per 100,000/y; there was a lower incidence of PSC in smokers 0.47 (0.33–0.61) per 100,000/y compared with those who had never smoked 0.95 (0.83–1.07) per 100,000/y. For AIH, there was no difference between current smokers and those who had never smoked

The authors speculate in the discussion about potential reasons why latitude could correlate with disease incidence. Some potential explanations include sunlight/vitamin D metabolism (though this is at odds with the fact that those with increased skin pigmentation are NOT at increased risk), environmental exposures (related to geology, diet, air quality) or unrecognized genetic tendency based on geography.

My take: In the UK, there is an association between a more northernly latitude and both PBC and AIH.

Related blog post: Aspen Webinar 2021 Part 5 -Autoimmune Liver Disease & PSC

Figure 2

FITCH Study of Bezafibrate for Pruritus Due to Cholestatic Liver Disease

In the Fibrates for Itch (FITCH) study, (E de Vries, R Bolier e al. Gastroenterol 2021; 160: 734-743. Full text pdf: Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies:A Double-Blind, Randomized, Placebo-Controlled Trial), the authors study bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist.

Key findings:

  • 70 patients completed the trial (44 PSC, 24 PBC, 2 SSC) (SSC =secondary sclerosing cholangitis). Treated patients received bezafibrate 400 mg once a day for 21 days.
  • For the primary end point, bezafibrate led in 45% (41% PSC, 55% PBC) and placebo in 11% to >/=50% reduction of severe or moderate pruritus (P ¼ .003).
  • Bezafibrate also reduced serum alkaline phosphatase (35%, P ¼ .03 vs placebo) correlating with improved pruritus (VAS, P ¼ .01) suggesting reduced biliary damage.
  • Serum bile acids and autotaxin activity remained unchanged.

My take: While the majority of patients did not reach the primary end point, bezafibrate merits further investigation and may be a useful agent for pruritus in the setting of cholestatic liver disease. From the associated editorial (pg 649, JK Dyson et al. Bezafibrate for the Treatment of Cholestatic Pruritus: Time for a Change in Management?): “FITCH is an important study and provides novel and important data. It suggests that bezafibrate can be part of the answer to cholestatic pruritus.”

From Editorial:

Current treatment ladder for pruritus and the potential positioning of bezafibrate in the future.

Related blog posts:

Yesterday’s post alluded to alcoholic liver disease. More on that topic from NPR:

Link: Sharp, ‘Off The Charts’ Rise In Alcoholic Liver Disease Among Young Women

Cases of alcoholic liver disease — which includes milder fatty liver and the permanent scarring of cirrhosis, as well as alcoholic hepatitis — are up 30% over the last year at the University of Michigan’s health system, says Dr. Jessica Mellinger, a liver specialist there….

In the U.S., more than 44,000 people died of alcoholic liver disease in 2019. And although liver diseases still affect more men, younger women are driving the increase in deaths, a trend that began several years ago and is now supercharged by the pandemic