Association of claudin2 and PRSS1-PRSS2 polymorphisms with idiopathic recurrent acute and chronic pancreatitis: A case-control study from India.

BACKGROUND: Gene polymorphisms, including those recently described in the claudin2 gene, have been implicated in recurrent acute (RAP) and chronic pancreatitis (CP). In India, RAP and CP have been associated with SPINK1 polymorphism. In this study, we evaluated the association of claudin2 and PRSS1-PRSS2 polymorphisms with idiopathic RAP and CP. METHODS: We included 101 prospectively followed patients with documented idiopathic RAP (IRAP) and 96 patients who presented with idiopathic chronic pancreatitis (ICP) without previous history of AP. Controls were 156 unrelated individuals undergoing master health check or with non-specific symptoms. All the samples were genotyped for the SNPs rs7057398 in the claudin2 (CLDN2) gene and rs10273639 in the PRSS1 gene on Realtime polymerase chain reaction platform. Clinical data pertaining to patient and disease characteristics were recorded. RESULTS: Claudin2 and PRSS1 polymorphisms were seen in a significantly higher proportion of female patients (P = 0.01 and 0.039, respectively). Thirty-three (32.7%) patients with IRAP developed features of early CP during follow-up (mean [95% confidence interval, CI] duration of 11.3 [8.9-13.7] months). Female patients with claudin2 (rs7057398) CC genotype were at significantly higher risk for IRAP (odds ratio [OR] [95% CI] 6.75 [1.82-23.67]; P = 0.004) and progression from IRAP to CP (OR [95% CI] 7.05 [1.51-33.01]; P = 0.007). CT genotype of PRSS1 (rs10273639) was associated IRAP (OR [95% CI] 2.59 [1.1-6.13]; P = 0.030), and both CT and CC genotypes with ICP in women (OR [95% CI] 2.86 [1.12-7.31]; P = 0.033 and 3.73 [1.03-13.59]; P = 0.048, respectively). CONCLUSION: In this study, we have demonstrated the association of claudin2 (rs7057398) polymorphism with IRAP and progression of IRAP to CP, and PRSS1 (rs10273639) polymorphism with IRAP and ICP.

Difference in lifestyle and metabolic profile of non-alcoholic fatty liver disease with raised alanine amino-transferases between obese and non-overweight subjects.

A significant proportion of patients with non-alcoholic fatty liver disease (NAFLD) in Asian sub-continent are non-overweight and may have different underlying risk factors, lifestyles and metabolic profiles. Seven hundred fifty patients of NAFLD with raised alanine-amino-transferase (ALT) were divided into non-overweight and obese group based on their body mass index (BMI). Detailed dietary and lifestyle history were obtained through questionnaires and a detailed assessment of metabolic profile and liver stiffness was done. Normal BMI (< 23 kg/m2) was found in 6.6% patients, of which 69.5% had raised ALT. Though the intake of dietary fat and exercise pattern were not different amongst these groups, yet the amount of aerated drinks was higher in obese subjects (12 ± 17 vs. 7 ± 7.5 p = 0.005). Serum low-density lipoprotein (111 ± 25.6 vs. 127.7 ± 32.7 p = 0.04) and insulin resistance based on HOMA-IR > 2 were significantly higher in obese group (4.1 ± 0.36 vs. 2.0 ± 0.15 p = 0.001). Insulin resistance and dyslipidemia were prevalent in 12% and 25% non-overweight patients respectively. Metabolic syndrome was more common in obese subjects. In addition, magnetic resonance elastography showed higher mean liver fat in the obese group with similar hepatic fibrosis. Non-overweight patients with NAFLD had lower insulin resistance and prevalence of dyslipidaemia at similar dietary and exercise pattern.

Long-term Outcome of Autologous Hematopoietic Stem Cell Infusion in Cirrhosis: Waning Effect over Time.

Background and Aims: Long-term data on cell-based therapies, including hematopoietic stem cell infusion in cirrhosis, are sparse and lacking. Methods: Patients with cirrhosis of non-viral etiology received either standard-of-care (n = 23) or autologous CD34+ cell infusion through the hepatic artery (n = 22). Study patients received granulocyte colony-stimulating factor (commonly known as G-CSF) injections at 520 µgm per day for 3 days, followed by leukapheresis and CD34+ cell infusion into the hepatic artery. The Control group received standard-of-care treatment. Results: Mean CD34+ cell count on the third day of G-CSF injection was 27.00 ± 20.43 cells/µL 81.84 ± 11.99 viability and purity of 80-90%. Significant improvement in the model of end-stage liver disease (commonly known as MELD) score (15.75 ± 5.13 vs. 19.94 ± 6.68, p = 0.04) was noted at end of 3 months and 1 year (15.5 ± 5.3 vs. 19.8 ± 6.4, p = 0.04) but was not statistically different at end of the second (17.2 ± 5.5 vs. 20.3 ± 6.8, p = 0.17) and third-year (18.4 ± 6.1 vs. 21.3 ± 6.4, p = 0.25). No difference in mortality (6/23 vs. 5/23) was noted. Conclusions: Autologous CD34+ cell infusion effectively improved liver function and MELD score up to 1 year but the sustained benefit was not maintained at the end of 3 years, possibly due to ongoing progression of the underlying disease.