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liver disease

AASLD meeting: liver disease and bariatric surgery

NAFLD Fibrosis Score is not an accurate predictor of fibrosis in bariatric patients
Bariatric surgery results in a reduction of fetuin-A in morbidly obese patients
Weight loss before surgery can result in alterations in liver histology

Several studies presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting in Boston, have provided new insights into the association between liver disease and bariatric surgery.

According to researchers from the Carolinas Medical Center, Charlotte, North Carolina, the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score is not an accurate predictor of fibrosis in bariatric patients,

The scoring method, developed in 2007 by Angulo et al (insert reference), is based on commonly attained serum measurements (AST/ALT ratio, albumin, platlelets), and patient information (age, BMI, history of diabetes).

Howver, after comparing NAFLD Fibrosis Score model and pathological scoring of biopsy samples of patients undergoing Roux-en-Y gastric bypass surgery, researchers reported that it is not an accurate predictor of the condition.

The aim of the study was to determine whether calculated NAFLD Fibrosis Scores could be accurately applied to patients with a BMI>40 awaiting Roux-en-Y surgery.

A total of 169 patients (mean BMI=44.6±5.4; 85% female) were involved in the study and biopsy samples were obtained and blind scored by a board certified Hepatopathologist according to established criteria.

Chart and serum measurements were obtained from patient records and NAFLD Fibrosis Scores calculated. Calculated data were stratified to the cut-off points for Low (no significant fibrosis), Indeterminate or High (significant fibrosis) groups based on the NAFLD Fibrosis Score. Data were then compared between biopsy and calculated values.

Using calculated NAFLD Scores, 68 patients (40.2%) fell into the Low group, 87 were Indeterminate (51.5%) and 14 were High (8.3%). Of those in the Low group 2/68 (2.9%) had significant fibrosis, while in the Intermediate groups, 3/87 (3.4%) exhibited significant fibrosis, by pathology scoring.

However in the High group only 4/14 (28.6%) exhibited significant fibrosis as determined by pathology. Within the Low group, sensitivity was 78% with 41% specificity and 2%/90% positive/negative predictive values.

In the High group sensitivity decreased to 44%, with 94% specificity and 29%/97% positive/negative predictive values. Further analysis of the groups revealed significant differences between groups by age and BMI, but not by gender or race.

The researchers also reported that incidence of type 2 diabetes was significantly greater in the High group than the Low.

fetuin-A reduction

Researchers from the University Hospital Essen, Germany, have reported that bariatric surgery resulted in a reduction of fetuin-A in morbidly obese patients with NAFLD.

Fetuin-A is a pro-inflammatory protein and a potent inhibitor of systemic calcification. However, the influence of weight loss as a result of bariatric surgery on fetuin-A expression in obese patients with NAFLD is not fully understood.

As a result, the researchers prospectively examined the effects of weight loss four weeks and six months after bariatric surgery. Blood and liver tissues were retrieved from 81 morbidly obese patients, with the serum of ten healthy volunteers serving as controls. Liver injury in patients was assessed histopathologically.

Overall, cell death and apoptosis were quantified via serum cytokeratin-18 (CK-18) (M65) or caspase-cleaved CK-18 fragments (M30), respectively, and confirmed by TUNEL-staining of index biopsies. Expression of fetuin-A was investigated by RT-qPCR, Western blot and immunohistochemistry, and serum concentrations of adiponectin and fetuin-A were determined by ELISA. Patients were grouped as non-alcoholic fatty liver (NAFL, M30<275U/l) or non-alcoholic steatohepatitis (NASH, M30>275U/l).

Six months after surgery, BMI decreased significantly from 52.8±0.8 to 36.7±0.9 in the NAFL group and from 53.2±1.1 to 36.3±1.0 in the NASH group (p<0.0001).

All patients with NASH revealed enhanced staining for TUNEL in liver tissue. This was associated with increased systemic cell death (M65) and apoptosis (M30) before surgery.

Following weight loss, the investigators witnessed a significant decline in M65 and M30 in NASH patients. RT-qPCR, Western blot and immunohistochemistry for fetuin-A revealed enhanced protein expression before surgery-induced weight loss compared with healthy controls.

In patients with NASH, plasma concentrations of fetuin-A significantly increased in the early post-surgery period but dropped below initial values after six months. Adiponectin, an anti-inflammatory adipokine, continuously increased after surgery in NASH patients.

The researchers concluded that bariatric surgery reduced hepatocyte apoptosis and increased adiponektin levels, suggesting diminished hepatic cell damage. Furthermore, surgery also led to a short term increase and later reduction of plasma fetuin-A. The preliminary data suggest that increasing fetuin-A expression in primary human hepatocytes after treatment with free fatty acids.

Liver histology

Weight loss before bariatric surgery can result in alterations in liver histology leading to under estimation of NASH and under staging of histological severity, according to researchers from Indiana University.

Morbidly obese individuals undergoing bariatric surgery are often prescribed liver reduction diet to induce weight loss before surgery. However, the effect preoperative weight loss has on liver histology is under-reported, the investigators claim.

To investigate the effect, liver biopsies were obtained from 95 consecutive patients who underwent bariatric surgery after following liver reduction diet with variable weight loss. Anthropometric data were collected on the day of screening visit (start of liver reduction diet) and on the day of bariatric surgery. The effect of weight loss was assessed on the diagnosis of NASH and other histological features including steatosis, lobular inflammation, ballooning degeneration, and fibrosis.

The mean age of the study population was 46.2+10.4 years (88% woman) with mean BMI of 45.7+6.9. The prevalence of NAFLD was 58% (steatosis=13% and NASH=45%) with 42% having relatively normal liver histology (not NAFLD).

There were no statistically significant differences in the anthropometric measures on the day of bariatric surgery in the three groups (BMI, weight and waist circumference). Among the three groups only preoperative weight loss showed a trend towards statistical significance (p=0.052).

The investigators reported that weight loss of more than 7% within one year was significantly associated with less frequent diagnosis of NASH (p=0.01), lower grades of lobular inflammation (p=0.01) and ballooning degeneration (p=.001). However, this degree of weight loss had no significant association with histological severity of steatosis (p=0.38) or degree of fibrosis (p=0.27).

They concluded that preoperative weight loss exceeding 7% is associated with alterations in liver histology leading to under estimation of NASH and under staging of histological severity.

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