Novel biomarkers of acute kidney injury in chronic liver disease: Where do we stand after a decade of research?

Acute kidney injury (AKI) is a frequently encountered complication in decompensated chronic liver disease (CLD) with an estimated prevalence of 20%-50% among hospitalized patients. AKI often heralds the onset of a downhill course in the natural history of CLD. Serum creatinine has several limitations as a stand-alone marker of AKI in patients with decompensated CLD. The concept of hepatorenal syndrome, the prototype of AKI in decompensated CLD, has evolved tremendously over recent years. There is emerging evidence of an additional "structural" component in the pathophysiology of hepatorenal syndrome-AKI, which was previously identified as a purely "functional" form of renal impairment. Lacunae in the existent biochemical arsenal for diagnosis and prognosis of AKI have fueled enthusiastic research in the field of novel biomarkers of kidney injury in patients with cirrhosis. The advent of these biomarkers provides a crucial window of opportunity to improve the diagnosis and clinical outcomes of this vulnerable cohort of patients. This review summarizes the dynamic concept of renal dysfunction in CLD and the available literature on the role of novel biomarkers of AKI in assessing renal function, identifying AKI subtypes, and predicting prognosis. There is special emphasis on the renal tubular injury marker, neutrophil gelatinase-associated lipocalin, the most exhaustively studied biomarker of AKI in the CLD population.

Issues associated with the emergence of coeliac disease in the Asia­Pacific region: a working party report of the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology.

BACKGROUND AND AIM: Once thought to be uncommon in Asia, coeliac disease (CD) is now being increasingly recognized in Asia­Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia. METHODS: A working group consisting of members from Asia­Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia­Pacific region both in terms of what exists and what needs to be done. RESULTS: The working group identified the gaps in epidemiology, diagnosis, and management of CD in Asian­Pacific region and recommended the following: to establish prevalence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized. CONCLUSIONS: Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia­Pacific region define extent of problem and get prepared to handle impending epidemic of CD.

Fibrosis in non-alcoholic fatty liver disease: correlation with simple blood indices and association with tumor necrosis factor-alpha polymorphisms.

AIM: The study was conducted with an aim to evaluate the clinico-pathological profile, the correlation of AST: ALT ratio and APRI with histological fibrosis, and the frequency of two specific polymorphisms (-238, -308) in the TNF alpha promoter region in patients with NAFLD. METHODS: The present study compared aspartate transaminase/alanine transaminase (AST/ALT) ratio and AST-to-platelet ratio index (APRI) with fibrosis score in 29 patients who underwent liver biopsy for NAFLD. Single nucleotide polymorphisms (SNP) in the tumor necrosis factor-alpha (TNF-alpha) promoter region at positions -308 and -238 were examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: AST/ALT ratio correlated better than the APRI with liver fibrosis in patients with NAFLD (AUROC of 0.9 compared to 0.68). TNF-alpha promoter region SNPs were present in only a minority of patients, and did not correlate with fibrosis severity. CONCLUSIONS: AST/ALT ratio correlated well with liver fibrosis in Indian patients with NAFLD. The SNPs studied had no role in development of fibrosis in Indian patients with NAFLD.

Urine neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury and prognosis in decompensated chronic liver disease: A prospective study.

BACKGROUND: Acute kidney injury (AKI) heralds deterioration in patients with decompensated chronic liver disease (DCLD). Serum creatinine (sCr), a component of the model for end-stage liver disease-sodium (MELD-Na) prognostic score, has limitations in patients with DCLD. We evaluated the prognostic role of urine neutrophil gelatinase-associated lipocalin (NGAL) in DCLD and its ability to sub-type AKI. METHODS: Total 147 consecutive patients hospitalized between June 2018 and June 2020 for complications of DCLD were evaluated. Urine NGAL was estimated and demographic, clinical and biochemical parameters recorded at baseline. Participants were followed up till the end of study period or mortality, whichever came earlier. Primary outcomes included all-cause mortality and time to death after index hospitalization. Secondary outcomes included the presence and type of AKI, need for intensive care unit (ICU) stay, length of ICU/hospital stay, in-hospital mortality, development of new-onset/recurrent AKI and recurrent hospitalization after index admission. RESULTS: Urine NGAL was highest in acute tubular necrosis (ATN), lowest in pre-renal azotemia (PRA) and intermediate in hepatorenal syndrome (HRS-AKI). Urine NGAL (p = 0.0208) was superior to sCr (p = 0.0388) and inferior to fractionated excretion of sodium (FENa) (p = 0.0013) in stratifying AKI. A cut-off of 203.9 ng/mL discriminated between HRS and PRA with sensitivity 77.8% and specificity 68.7%. Urine NGAL correlated with MELD-Na score, need for ICU stay, in-hospital mortality and mortality at three and six months. Two-year survival was significantly lower in patients with urine NGAL > 205 ng/mL. Addition of log-urine-NGAL score did not improve predictive performance of MELD-Na. CONCLUSION: Urine NGAL could identify AKI sub-types and correlated with short-term clinical outcomes, including mortality.

Inflammatory bowel diseases in Tamil Nadu: A survey of demographics, clinical profile, and practices.

BACKGROUND: Inflammatory bowel disease (IBD) is increasingly diagnosed in South Asia. This survey by the Tamil Nadu Chapter of the Indian Society of Gastroenterology (TNISG) documents the demography, clinical profile, and therapeutic practices related to IBD in Tamil Nadu. METHODS: TNISG members from 32 institutions completed an online cross-sectional questionnaire on IBD patients from March 2020 to January 2021. RESULTS: Of 1295 adult IBD patients, 654 had Crohn's disease (CD), 499 ulcerative colitis (UC), and 42 IBD-unclassified (IBD-U). CD and UC showed a unimodal age distribution. A total of 55% were graduates or postgraduates. A positive family history was noted in 30, other risk factors were uncommon. In CD, the pattern of involvement was ileocolonic (42.8%), ileal (34.7%), colonic (18.9%), and upper gastrointestinal (3.5%); while in UC, disease was characterized as extensive (44.9%), left-sided (41.7%), or proctitis (13.4%). Perineal disease, perianal fistulae, and bowel obstruction were noted in 4.3, 14.0, and 23.5%, respectively, of CD. The most widely used drugs were mesalamine, azathioprine, and corticosteroids. Surgery was undertaken in 141 patients with CD and 23 patients with UC. Of the 138 patients with pediatric IBD (≤16 years), 23 were characterized as very early onset IBD (VEO-IBD), 27 as early-onset, and 88 as adolescent IBD. VEO-IBD were more likely to have a positive family history of IBD and were more likely to have perineal disease and to have the IBD-U phenotype. Among pediatric IBD patients, corticosteroids, mesalamine, and azathioprine were the most commonly used medications, while 25 pediatric patients received biologics. CONCLUSION: This study provides important information on demography, clinical profile, and treatment practices of IBD in India.

Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor.

IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.

Prevalence and factors associated with gastroesophageal reflux disease in southern India: A community-based study.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is common worldwide with significant expenditure for health care. Community-based data on the prevalence of GERD in India remains scarce. This study was conducted to determine the prevalence of GERD and to identify potential associations. METHODS: A community-based survey of adults (aged ≥18 years) was done through population proportionate to size sampling in urban and rural areas of Vellore district, Tamil Nadu, India. GERD was defined as heartburn and regurgitation occurring at least twice per week. Associations between GERD and gender, age, anthropometric measures, and consumption of tobacco, alcohol, meat, and milk were evaluated. Odds ratios (OR) with 95% confidence intervals were derived from logistic regression models. RESULTS: Of 6174 participants (3157 urban, 2599 male), 8.2% had GERD. The prevalence was higher in urban (11.1%) compared to rural areas (5.1%) (p < 0.001). Among patients with GERD, 34.3% used medications daily for symptom relief. On univariate analysis, GERD was associated with female gender, living in an urban area, age >30, BMI >25, and infrequent milk consumption. On multivariate analysis, female gender (OR 1.3; 95% CI 1.1-1.6), living in urban area (OR 2.3; 95% CI 1.9-2.8), age >30 years (OR 1.9; 95% CI 1.4-2.5), BMI ≥ 25 kg/m2 (OR 1.3; 95% CI 1.1-1.6), and infrequent milk intake (OR 1.6; 95% CI 1.3-1.9) were independently associated with GERD. CONCLUSION: Symptomatic GERD was found in 8.2% of respondents in this representative southern Indian community, being more prevalent in urban residents, women, older, and obese individuals.

Comparison of a sports-hydration drink containing high amylose starch with usual hydration practice in Australian rules footballers during intense summer training.

BACKGROUND: Fluid deficits exceeding 1.6% can lead to physical and cognitive impairment in athletes. Sport drinks used by athletes are often hyper-osmolar but this is known to be suboptimal for rehydration in medical settings and does not utilize colonic absorptive capacity. Colonic absorption can be enhanced by fermentative production of short chain fatty acids (SCFA) from substrates such as high amylose maize starch (HAMS). This study therefore compared, in elite Australian Football League (AFL) players at the height of outdoor summer training, a novel dual-action sports oral rehydration strategy that contained HAMS as well as glucose, to their usual rehydration practices (Control). The primary outcome markers of hydration were hematocrit and body weight. METHODS: A randomized single-blind crossover study was undertaken in thirty-one AFL players; twenty-seven completed the study which was conducted on four days (two days in the Intervention arm and two in Control arm). The Intervention arm was comprised a 50-100 g evening preload of an acetylated HAMS (Ingredion Pty Ltd) followed by consumption of a specially formulated sports oral rehydration solution (SpORS) drink during intense training and recovery. Players followed their usual hydration routine in the Control arm. Quantitative assessments of body weight, hematocrit and urine specific gravity were made at three time-points on each day of training: pre-training, post-training (90 min), and at end of recovery (30-60 min later). GPS tracking monitored player exertion. RESULTS: Across the three time-points, hematocrit was significantly lower and body weight significantly higher in Intervention compared to Control arms (p < 0.02 and p = 0.001 respectively, mixed effects model). Weights were significantly heavier at all three assessment points for Intervention compared to Control arms (Δ = 0.30 ± 0.13, p = 0.02 pre-training; Δ = 0.43 ± 0.14, p = 0.002 post training; and Δ = 0.68 ± 0.14, p < 0.001 for recovery). Between the pre-training and end-of-recovery assessments, the Control arm lost 0.80 kg overall compared with 0.12 kg in the Intervention arm, an 85% lower reduction of bodyweight across the assessment period. CONCLUSION: The combination of the significantly lower hematocrit and increased body weight in the Intervention arm represents better hydration not only at the end of training as well as following a recovery period but also at its commencement. The magnitude of the benefit seems sufficient to have an impact on performance and further studies to test this possibility are now indicated. TRIAL REGISTRATION: Trial is listed on the Australian New Zealand Clinical Trials Registry ( ACTRN 12613001373763 ).