Sacroiliitis, NAFLD, IMIDs -Concurring Problems with Inflammatory Bowel Disease

I Levine et al. Inflamm Bowel Dis 2021; 809-815. Prevalence, Predictors, and Disease Activity of Sacroiliitis Among Patients with Crohn’s Disease

Key findings in this cross-sectional retrospective study (n=258, median age 30 yrs):

  • Overall, 17% of patients had MRI evidence of sacroiliitis, of whom 73% demonstrated bone marrow edema.
  • Female gender, back pain, and later age of CD diagnosis were associated with sacroiliitis (P = 0.05, P < 0.001, P = 0.04, respectively).
  • Disease activity (clinical, endoscopic, and radiographic), disease location and CD therapy were not associated with sacroiliitis on MRE.
  • More than two-thirds with MRE evidence of sacroiliitis were never seen by a rheumatologist.

A Lin et al. Inflamm Bowel Dis 2021; 947-955. Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Key finding:

  • Data pooled from 27 studies showed the prevalence of NAFLD among IBD patients was 32% (substantial heterogeneity); this is “statistically significantly higher than the prevalence of NAFLD in the general population (25.2%; P < 0.001)”

M Attauabi et al. Inflamm Bowel Dis 2021; 927-939. Systematic Review with Meta-analysis: The Impact of Co-occurring Immune-mediated Inflammatory Diseases on the Disease Course of Inflammatory Bowel Diseases

A total of 93 studies were identified, comprising 16,064 IBD patients with co-occurring IMIDs and 3,451,414 IBD patients without IMIDs. IMIDs included the following:

  • Unspecified autoimmune disease
  • Diabetes type 1
  • Asthma
  • Grave disease
  • Spondyloarthropathy
  • Ankylosing spondylitis
  • Iridocyclitis
  • Uveitis
  • Rheumatoid arthritis
  • Polymyalgia rheumatica
  • Psoriasis/psoriatic arthritis
  • Primary Sclerosing Cholangitis
  • Celiac disease
  • Pyoderma gangrenosum
  • Pernicious anemia
  • Autoimmune hepatitis
  • Sarcoidosis
  • Giant cell arteritis
  • Primary biliary cholangitis
  • Hashimoto thyroiditis
  • Episcleritis
  • Sjogren syndrome

Key findings: Patients with IBD and co-occurring IMIDs were at increased risk of having extensive colitis or pancolitis (risk ratio, 1.38; 95% Cl, 1.25–1.52; < 0.01, I2 = 86%) and receiving IBD-related surgeries (risk ratio, 1.17; 95% Cl, 1.01–1.36; P = 0.03; I2 = 85%) compared with patients without IMIDs

Image below from Bahia Honda State Park (FL)

Increased Cancers with Fatty Liver Disease

Z Wang et al. Clin Gastroenterol Hepatol 2021; 19: 788-796. Associations Between Nonalcoholic Fatty Liver Disease and Cancers in a Large Cohort in China

It is well-recognized that obesity/overweight increases the risk of cancer (related blog post: Cancer due to Overweight/Obesity). Wang et al provide data regarding cancer risk due specifically to nonalcoholic fatty liver disease (NAFLD) from a large prospective adult cohort (n=54,187). Key findings:

  • Prevalence of NAFLD, based on ultrasonography, was 32.3%.
  • NAFLD was associated with increased risk of all cancers (hazard ratio [HR], 1.22; 95% CI, 1.10–1.36; P = .0001), thyroid cancer (HR, 2.79; 95% CI, 1.25–6.21; P = .01), and lung cancer (HR, 1.23; 95% CI, 1.02–1.49; P = .03).
  • Increased risk for colorectal cancer (HR, 1.96) and lung cancer (HR, 1.38) was demonstrated only in smokers.  An association between NAFLD and kidney cancer (HR, 1.57; 95% CI, 1.03–2.40) was only observed in men without diabetes.
  • Risk of hepatocellular carcinoma was increased only in those with elevated ALT values of 80 U/L or more (HR 8.08)

My take: This study shows that NAFLD increases the risk of cancer; much of this risk may be due to obesity/metabolic syndrome and associated chronic inflammation. Overall, cardiovascular disease in patients with NAFLD represents a higher risk for morbidity and mortality.

Related blog posts:

Peonies

Juice in Infancy and Fatty Liver Disease

Briefly noted: ML Geurtsen et al. Hepatology 2021; 73: 560-570. Full text: Associations Between Intake of Sugar‐Containing Beverages in Infancy With Liver Fat Accumulation at School Age

Methods: In a population‐based prospective cohort study of 1,940 infants, we assessed sugar‐containing beverage intake (juice or soda) at 1 year with a validated Food Frequency Questionnaire. Liver fat fraction and NAFLD (liver fat fraction ≥5.0%) were assessed with MR. Key findings:

  • Compared to infants with <1.0 serving/day, those with >2.0 servings/day had the highest odds of NAFLD at 10 years of age (OR, 3.02; 95% CI, 1.34, 6.83). This was independent of sugar‐containing beverage intake and body mass index at school age
  • Liver fat fraction greater than or equal to 5% in school-aged children was almost 3-fold higher in those who consumed more than two servings of juice per day at age 1 (4.0%) than in those who drank less than one per day (1.4%)
  • The associations between juice intake in infancy and NAFLD were strongest in children with overweight or obesity at age 10 and those in families with more limited education

Major strengths of this study are the population‐based prospective longitudinal design with a large sample size, with information on sugar‐containing beverage intake in infancy and liver fat fraction measured with MR at 10 years of age.

My take: Juice and other high sugar beverages (eg soda) should be avoided, particularly at younger ages.

Related blog posts:

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Best Practice for Fatty Liver Disease

ZM younossi, KE Corey, JK Lim. Gastroenerol 2021; 160; 912-918. AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review

Some of the Best Practice Advice Recommendations:

  • #1 “Lifestyle modification using diet and exercise to achieve weight loss is beneficial for all patients with nonalcoholic liver disease (NAFLD).”
  • #2 Weight loss leads to improvement. >5% wt loss can decrease steatosis, >7% can lead to resolution of NAFLD, >10% can stabilize or reduce fibrosis
  • #3 “Adults with NAFLD should follow the Mediterranean diet…as well as limit or eliminate consumption of commercially produced fructose”
  • #8 Evaluate for coexisting conditions, such as “obesity, diabetes mellitus, hypertension, dyslipidemia and cardiovascular disease.”

Also another publication on fatty liver disease:

LF Chun et al. J Pediatr 2021: https://doi.org/10.1016/j.jpeds.2021.01.064. Hepatic Steatosis is Negatively Associated with Bone Mineral Density in Children

Related blog posts:

Progression of Fatty Liver Disease in Children

SA Xanthakos et al. Gastroenterol 2020; 159: 159: 1731-1751. Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice

This prospective study followed the natural history of NAFLD in children with timed liver biopsy reassessment in children (n=122) using the placebo arms of 2 large multicenter clinical trials; patients received standard of care lifestyle advice. The study population had a mean age of 13 years; 71% were Hispanic participants

Key findings:

  • At enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH
  • Over a mean period of 1.6 ± 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH
  • Fibrosis improved in 34% of the children but worsened in 23%
  • Progression was more likely with increasing ALT, increasing GGT, type 2 diabetes/increasing HgbA1c
  • Overall, one-third had histologic features of progression within 2 years, in association with increasing obesity and serum levels of aminotransferases and loss of glucose homeostasis.
  • The study conclusions are limited by selection bias, potential liver biopsy sampling errors, limited enrollment of non-Hispanic children, and relatively short duration of follow-up

Related blog posts:

Genetic Testing for Fatty Liver Disease Is Not Ready For Routine Use

A recent study (H Gellert-Kristensen et al. Hepatology 2020; 72: 845-856. Combined Effect of PNPLA3TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population) describes genetic risk score (GRS) which can stratify the risk of developing cirrhosis and hepatocellular carcinoma.

The study utilized data and plasma markers from 110,761 individuals from Copenhagen, Denmark, and 334,691 individuals from the UK Biobank. GRS scores were from 0 to 6 based on three common genetic variants: PNPLA3, TM6SF2, and HSD17B13.

Key finding:

  • A GRS of 5 or 6 (compared to GRS of 0) for fatty liver disease confers up to a 12‐fold higher risk of cirrhosis and up to a 29‐fold higher risk of HCC in individuals from the general population

The editorial by RM Pfeiffer et al (Hepatology 2020; 72: 794-795. Genetic Determinants of Cirrhosis and Hepatocellular Carcinoma Due to Fatty Liver Disease: What’s the Score?) is very helpful in placing the findings in context.

  • Only 0.5% of individuals had a GRS of 5 or 6. “A GRS of 4 [or more] which still conveyed large risks (cirrhosis, OR =5.2; HCC, OR =3.3) was found in approximately 5% of this population.”
  • Using a GRS of 4 or more, the positive predictive value of GRS-based test in the Danish population is “0.008 for cirrhosis and 0.003 for HCC. In other words, among 1000 persons with GRS greater than or equal to 4, only 8 will develop cirrhosis and 3 will develop HCC.”

My take: This study confirms that specific genetic variants increase the risk of complications from fatty liver disease. However, poor predictive value will likely preclude routine application.

Prenatal Liver Pollutants: Perfluoroalkyl Substances

It is very difficult to try to understand potential toxic substances in our environments. Some of the reasons for this are that there are always numerous simultaneous exposures and harm from substances can accrue over long periods. Once a substance is identified, it can take a long time to develop convincing evidence and even longer time frames to try to enact policy changes.

Despite these challenges, fortunately researchers continue to try to tease out these dangerous agents. A recent study (N Stratakis et al. Hepatology 2020; 72: 1758-1770. Free Full text: Prenatal Exposure to Perfluoroalkyl Substances Associated With Increased Susceptibility to Liver Injury in Children)

Background/Methods: Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been shown to have hepatotoxic effects in animal models. However, human evidence is scarce. PFAS chemicals have a myriad industrial/household applications which include nonstick cookware and products that confer resistance to stains. According to the editorial (MC Cave, pg 1518-21), some refer to PFAS as “forever chemicals” due to their decades-long half-lives.

The study authors used data from 1105 mothers and their children (median age 8.2 years) from the European Human Early-Life Exposome cohort. Key findings:

  • High prenatal exposure to PFAS resulted in children who were at higher risk of liver injury (odds ratio, 1.56; 95% confidence interval, 1.21–1.92)
  • PFAS exposure is associated with alterations in key amino acids and lipid pathways characterizing liver injury risk.

Related blog posts:

Fatty Liver Disease in Children is Increasing

AK Sahota et al. Pediatrics 2020; DOI: https://doi.org/10.1542/peds.2020-0771. Incidence of Nonalcoholic Fatty Liver Disease in Children: 2009–2018

Key finding:  The incidence of an NAFLD diagnosis significantly increased over time, with 36.0 per 100 000 in 2009 and 58.2 per 100 000 in 2018 (P < .0001), based on study of a large integrated health care system in southern California

Help Wanted in Hepatology

MW Russo et al. Hepatology 2020; 72: 1444-1454. Modeling the Hepatology Workforce in the United States: A Predicted Critical Shortage

Overall, this article details the estimated shortage of hepatologists in the coming years.

Key points:

  • One of the more interesting suggestions in this article is the need to change the name of specialty training from “transplant hepatology” to “advanced hepatology” to more accurately reflect the type of liver conditions managed by hepatologists.
  •  In 2018, the adult and pediatric workforce included 7,296 and 824 hepatology providers, respectively, composed of hepatologists, gastroenterologists, and advanced practice providers whose practice was ≥50% hepatology
  • The modeling analysis projects that in 2023, 2028, and 2033, there will be shortages of 10%, 23%, and 35% adult hepatology providers, respectively, and 19%, 20%, and 16% pediatric hepatology providers, respectively

The authors note that there are many challenges when predicting workforce needs. The main reasons for the predicted shortfall with hepatology include the following:

  • Older age of current clinicians
  • Increasing amount of liver disease (~34% increase from 2018 to 2033), particularly fatty liver disease. This is happening among adults and children.

Related blog post: Sad Truth: Job Security in Hepatology

From The Onion

Liver Shorts -November 2020 and Georgia’s ACA Waiver

E Zuckerman et al. Clin Gastroenterol Hepatol 2020; 18: 2544-53. Full text link: Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection

  • “We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir.” (n=1248) Key finding:  Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations.

JA Silverman et al. JPGN 2020; 71: 283-287. Composite Lipid Emulsion for the Infant at Risk of Intestinal Failure–associated Liver Disease: The Canadian Perspective

This review discussed the use of SMOFlipid that includes soybean, medium-chain triglycerides, olive and fish oils. Key points:

  • “Lipid minimization strategies have also been shown to reverse IFALD [intestinal failure associated liver disease]. There are, however, considerable concerns regarding adequate weight gain, compromise to neurodevelopment, and EFAD [essential fatty acid deficiency]”
  • “Thee is actually considerable safety data for CLE [composite lipid emulsion] in neonates, albeit over the short term.”
  • “In Canada, CLE is currently the lipid emulsion of choice for all infants at risk of IFLAD.”

T Mitchell et al. Clin Gastroenterol Hepatol 2020; 18: 1584-1591. Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron Availability

  • Methods: “We collected information on weight-adjusted, submaximal physical work capacity (PWC), ultrasound-determined hepatic steatosis, iron indices, and hematologic and metabolic parameters from 390 female and 458 male participants of the Raine Study—a longitudinal study of disease development … in Western Australia”
  • Key finding: “Fourteen percent of the cohort had NAFLD. PWC was significantly reduced in adolescents with NAFLD compared to adolescents without NAFLD (reduction of 0.17 W/kg, P = .0003, adjusted for sex and body mass index [BMI])… we found NAFLD to be associated with decreased cardiorespiratory fitness, independent of BMI. The relationship between transferrin saturation and PWC in adolescents with NAFLD indicates that functional iron deficiency might contribute to reductions in cardiorespiratory fitness.”

In other news, Georgia has received approval for an affordable care act waiver. From the AJC (October 15, 2020): Kemp’s health care waivers win federal approval Two key points:

  • “Thousands of Georgia’s poor and uninsured adults who meet a work or activity requirement will soon be eligible for Medicaid, with perhaps 50,000 added to the rolls within two years…And more than 350,000 very poor, uninsured Georgia adults still won’t meet Georgia’s requirements for Medicaid”
  • “At the same time, the 400,000 Georgians who bought individual health insurance plans on the federal healthcare.gov Affordable Care Act shopping website will find they can’t do that anymore. Instead they will be directed to contact information for private brokers or insurance companies”
These tweets were posted on 11/2/20.