Acute Liver Failure Due to Etodolac, a Selective Cycloxygenase- 2 (COX -2) Inhibitor Non-Steroidal Anti-Inflammatory Drug Established by RUCAM-Based Causality Assessment.

Drug induced liver injury is a common cause of acute liver failure (ALF). While most of these cases are due to dose dependent hepatotoxicity with acetaminophen, idiosyncratic drug-induced liver injury (DILI) is responsible for about 15% cases of ALF. Antibiotics are the most common cause of idiosyncratic DILI as well as DILI induced ALF. Etodolac is a selective cycloxygenase- 2 (COX -2) inhibitor non-steroidal anti-inflammatory drug used as an analgesic and anti-inflammatory in musculoskeletal diseases. Severe liver impairment is extremely rare. Till date, only 3 cases of ALF related to etodolac have been reported in the literature. Here we report two cases with a unique presentation of ALF occurring due to DILI caused by etodolac, as diagnosed by Roussel Uclaf Causality Assessment Method (RUCAM).

Correlation of adipose tissue with liver histology in Asian Indian patients with nonalcoholic fatty liver disease (NAFLD).

BACKGROUND: There is sparse literature on the association of adipose tissue with liver histology in patients with nonalcoholic fatty liver disease (NAFLD). AIM: To study the correlation of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) with liver histology in Indian patients with NAFLD. MATERIAL AND METHODS: A single slice CT scan at the level of L4-L5 vertebrae was done to assess the abdominal VAT and SAT volumes in 21 patients with histological diagnosis of NAFLD. Adult treatment panel III criteria with modified abnormal waist were used to define metabolic syndrome (MS). Histological grading was done according to the NAFLD activity score (NAS). RESULTS: Twenty-one patients with NAFLD [13 males, median age: 35 years, median BMI: 25.97 kg/m(2)] were included prospectively. Even though overweight/obese patients had severe liver disease, there was no difference in the volume of VAT adjusted for BMI between 6 (28.5%) lean and 15 (71.5%) overweight/obese patients. Patients with NASH and borderline NASH were older, obese with higher VAT and SAT volumes than no-NASH group. SAT volume (SATV) correlated significantly with hepatic steatosis but none of the adipose tissue volumes had any correlation with other histological variables. Both SATV and TAT volume (TATV) correlated significantly with severity of liver disease as determined by NAS score whereas presence of MS or insulin resistance had no correlation with histological severity. CONCLUSION: Both subcutaneous and total adipose tissue volume are related to the disease severity as determined by NAFLD activity score in Indian patients with NAFLD.

Chemical shift magnetic resonance imaging is helpful in detecting hepatic steatosis but not fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

BACKGROUND & AIM: Imaging modalities have a role in the diagnosis of patients with nonalcoholic fatty liver disease. Aim of the present study was to evaluate the role of chemical shift magnetic resonance imaging in assessing hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease. METHODS: Chemical shift magnetic resonance imaging was done in 10 biopsy proven patients (7 females, mean age 41 +/- 9.2 years) with nonalcoholic fatty liver disease. Objective measurements of signal intensity (SI) were done and a ratio was calculated (SI out-of- phase liver/ SI out-of- phase kidney)/ (SI in- phase liver/ SI in-phase kidney). A lower ratio indicated a higher signal drop and hence higher fat content. The ratio was correlated with hepatic steatosis on histology (< 33% and > 33%). Patients were classified as having histological NASH or no NASH and MRI was assessed in diagnosing hepatic fibrosis as seen on liver histology. RESULTS: Six patients had > 33% hepatic steatosis on histology. Five patients (50%) had evidence of histological NASH. MRI was not helpful in differentiating patients with and without histological NASH. One patient amongst NASH patients did not have fibrosis, one had stage 1, 2 had stage 2 and one had stage 4 fibrosis. SI ratio ranged between 0.35-0.69 in 6 patients with steatosis > 33% and was in the range of 0.69-1.20 in four patients with steatosis < 33% on histology. Fibrotic changes seen in 4 patients on biopsy were not detected on MRI. CONCLUSION: Chemical shift MRI provides objective data on fat infiltration in patients with NAFLD without giving information about hepatic fibrosis.

Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions.

BACKGROUND: Insulin resistance plays an important role in the pathogenesis of NAFLD. Pharmacological treatment of patients with NAFLD is still evolving. Insulin sensitizing drugs like metformin may be effective in these patients. Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases (ALT) after 6 months of lifestyle interventions and UDCA were treated with metformin 500mg tid for 6 months. Insulin resistance was determined by HOMA- IR. Liver function tests were done monthly and patients were defined having no response, partial response or complete biochemical response depending on the change in ALT. Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions (disease controls). RESULTS: Thirteen (52%) patients had class III (n = 5) or class IV (n = 8) disease amounting to histological NASH. Of these 13 patients none had severe inflammation and none had stage 4 fibrosis (cirrhosis). All 25 patients with NAFLD had insulin resistance in comparison to healthy controls. In comparison to disease controls (127.5 +/- 41.8 vs. 118 +/- 21.6 p = NS), all patients treated with metformin had partial biochemical response (mean ALT 122.2 +/- 26.8 vs 74.3 +/- 4.2 p < 0.01) and 14 (56%) of them achieved complete normalization of ALT. CONCLUSIONS: Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions and UDCA.