A recent systematic review and meta-analysis (Y Lee, et al. Clin Gastroenterol Hepatol 2019; 17: 1040-60) included 32 cohort studies with 3093 liver biopsy specimens from patients with nonalcoholic fatty liver disease (NAFLD).
- Bariatric surgery resulted in a biopsy-confirmed resolution of steatosis in 66%, inflammation in 50%, ballooning degeneration in 76%, and fibrosis in 40%.
- Bariatric surgery resulted in worsening features of NAFLD in 12%.
- The authors note that Roux-en-Y Gastric Bypass (RYGB) “showed greater reduction of liver side effects and higher: resolution of NAFLD.”
- Jejejnoileal bypass (JIB) and biliopancreatic diversion (BPD) “both have been associated with higher liver function morbidity.”
- The overall GRADE quality of evidence was considered very low.
My take: Though better studies are needed, the majority of patients’ livers appear to benefit from bariatric surgery.
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According to a recent study (EL Yu et al. J Pediatr 2019; 207: 64-70), about one-third of boys and one-fourth of girls with obesity have nonalcoholic fatty liver disease (NAFLD).
This study from San Diego with 408 children aged 9-17 years (mean 13.2 years) with obesity evaluated for NAFLD with laboratories (to exclude other etiologies) and with liver MRI proton density fat fraction (PDFF), with ≥5% considered the threshold for NAFLD.
- Prevalence of NAFLD was 26% in this population, with 29.4% in males and 22.6% in females
- The optimal cut offs of ALT for detecting NAFLD in this study were ≥30 U/L for females and ≥42 U/L for males. These are much lower than NASPGHAN guidelines which proposed ≥80 U/L or twice the ULN as thresholds for further investigation. (The NASPGHAN recommendations are likely to have higher specificity in identifying children at greater risk for nonalcoholic steatohepatitis (NASH).)
- 77% of this cohort were hispanic, thus prevalence may vary significantly in other populations.
- MRI-PDFF -the exact cut off is unclear. The authors note that if 3.5% were chosen, the NAFLD prevalence jumped to 49.3% (according to Table II –though the discussion stated 53.2%)
My take: Understanding the likelihood of NAFLD in children at risk is a helpful first step. This study points to the growing use of non-invasive diagnosis with MRI.
On a related topic, briefly noted: “Obesity in Adolescents and Youth: The Case for and against Bariatric Surgery” (A Khattab, MA Sperling. J Pediatr 2019; 207: 18-22). In this review, the authors refer frequently to endocrine society guidelines (J Clin Endocrinol Metab 2017; 102: 709-57). These guidelines generally recommend bariatric surgery only under specific conditions (eg. completion of Tanner 4 or 5 along with a BMI of 40 kg/m-squared or BMI of 35 with significant extreme comorbidities after failure of lifestyle modifications & without untreated psychiatric illness). This review predicts increasing use of bariatric surgery in adolescents “as more data on long-term outcomes in larger cohorts become known.”
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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.
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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)
A recent study (D Kim et al. Gastroenterol 2018; 155: 1154-63) used a CDC database which captures >99% of deaths in the U.S. to analyze mortality trends from 2007 through 2016. Full text link available online: Changing Trends in Etiology-Based Annual Liver Mortality
When looking at all-cause mortality, there has been a significant decline in deaths associated with hepatitis C (HCV) but not in deaths associated with alcoholic liver disease (ALD). The image below shows the trend and the impact of direct-acting antivirals. Deaths associated with nonalcholic fatty liver disease (NAFLD) and due to hepatitis B (HBV) are described in this study as well, though both together account for less than 1/4th deaths associated with ALD. Interestingly, mortality related to NAFLD was increasing slowly over the study period.
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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.
- 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.
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Tea House Trail, near Lake Louise, Banff
Briefly noted: V Ajmera et al. Clin Gastroenterol Hepatol 2018; 16: 1511-20. This study with 285 participants showed that modest alcohol consumption was associated with a lower odds of NASH resolution on biopsy over 4 years compared with no alcohol consumption (OR 0.32). The associated editorial (pg 1404-6) provides a table with 8 studies that reveal conflicting results on this issue.
My take (borrowed from editorial): “Clinicians should not recommend modest drinking” as a way of improving liver health.
Related review article:D Fuster, JH Samet. “Alcohol Use in Patients with Chronic Liver Disease” NEJM 2018; 379: 1251-61. For NAFLD (and all chronic liver disease): “abstinence should be the goal.”
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Lake Moraine, Banff
A recent autopsy study (DM Fernandes et al. J Pediatr 2018; 200: 174-80) examined nonalcoholic fatty liver disease (NAFLD) in a pediatric cohort of 582 (2-19). Approximately 75% were in 14-19 years of age and 50% were black; black pediatric patients (n=290) were over-represented in this sample only 25% of the New York population is black or African American based on the 2010 census.
- Causes of death: 49% homicides, 31% accidents, 10% acute illness, 9% suicide, 1% other
- Overall, NAFLD was present in 4.5%; this low overall prevalence was due in part to the low rate of NAFLD in black children; only 3 of 290 (1%) had NAFLD and none had nonalcoholic steatohepatitis (NASH)
- The rate of NAFLD was 7.9% in hispanics and 8.3% in white patients.
- In this cohort, 36% were overweight or obese. In this subgroup, 14.1% of hispanics and 14.8% of whites had NAFLD.
- Overall, NASH was present in 1.7% of the entire cohort. NASH and fibrosis have been shown in prior studies as the best predictors of disease progression
My take: If black children are not killed by homicide or accidents, it is unlikely that they will die from NAFLD due to its low prevalence.
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Sunshine Meadows, Banff