Gluten-free foods are expensive and nutritionally imbalanced than their gluten-containing counterparts.

OBJECTIVES: Nutritional quality of gluten-free (GF) food products is very important, as patients with celiac disease consume these products for lifelong. There is paucity of data on the nutritional content and cost of GF food products compared with their gluten-containing (GC) counterparts from India (Asia). DESIGN: After a detailed market survey, packaged and labeled GF food products (n=485) and their packaged GC counterparts (n=790) from the supermarkets of Delhi (India) and e-commerce websites were included. Nutritional content and cost/100 g food (in US dollars) were calculated using the information on food label. RESULTS: Gluten-free food products were 232% (range: 118% to 376%) more expensive than their GC counterparts. Energy content of all GF food products was similar to their GC counterparts, except cereal-based snacks (GF: 445 kcal vs. GC: 510 kcal, p<0.001). The protein content was significantly lower in GF pasta and macaroni products (single-grain: GF: 6.5 g vs. GC:11. 5 g, p-0.002; multigrain: GF:7.6 g vs. GC:11.5 g, p-0.027), cereal flours (single-grain: GF: 7.6 g vs. GC: 12.3 g, p<0.001; multigrain: GF:10.9 g vs. GC: 14.1 g, p-0.009) and nutritional bars (GF: 21.81 g vs. GC:26 g, p-0.028) than their GC counterparts. Similarly, the dietary-fiber content of GF pasta and macaroni products, cereal flours, cereal premix and nutritional bars of GF foods was significantly lower than their GC counterparts. Gluten-free bread and confectionary items, biscuits and cookies and snacks had higher total fats and trans-fat content than their GC counterparts. Gluten-free cereal-based snacks had higher sodium content than their GC counterparts (GF: 820 mg vs. GC:670 mg; p<0.001). CONCLUSION: GF foods are significantly more expensive, contain less protein and dietary fiber and higher fat, trans-fat and sodium than their GC counterparts. Strategies must be developed to reduce the cost and improve the nutritional profile of GF foods.

Longitudinal changes in bone mineral density may be associated with long-term survival in patients with cirrhosis: A proof of concept of study.

INTRODUCTION: The impact of longitudinal changes in different body components measured via body composition analysis (BCA) on liver-related outcomes in patients with cirrhosis is poorly understood. We evaluated the prognostic relevance of longitudinal changes in body composition over one year in patients with cirrhosis. METHODS: This was a follow-up study of a randomized controlled trial evaluating changes in bone density measured via dual energy X-ray absorptiometry (DEXA) upon vitamin D supplementation. Patients with available anthropometric indices, fat mass (FM), fat-free mass (FFM), bone-density at lumbar spine (LD) and left femur-neck (FD) (assessed by T score) at two time points one year apart were assessed for outcomes. The prognostic relevance of change in parameters such as ΔFM, ΔFFM, ΔLD and ΔFD over one year was assessed and compared with baseline model for end-stage liver disease (MELD) score. RESULTS: Patients with cirrhosis (n=112) (mean age 41.8±12 years, 58.5% males) were followed up for median duration of 5.7 years interquartile range [IQR 3.5-5.7], with five-year survival rate of 77%. On serial BCA, ΔLD (p=0.029) and ΔFD (p=0.003) emerged as significant predictors of survival, whereas ΔFM (p=0.479), ΔFFM (p=0.245) and ΔBMI (p=0.949) were not. The area under curve of ΔLD and MELD score for predicting survival was 0.636 (0.5-0.773) and 0.664 (0.555-0.773), respectively. ΔFD<0.1 over one year had sensitivity and specificity of 70.4% and 56.5% to predict poor survival. The combination of ΔFD, MELD and ascites predicted five-year survival with an optimism-corrected c-statistic of 0.785. CONCLUSION: Among body composition parameters, changes in bone mineral density correlate best with survival and have prognostic relevance similar to that of ascites and MELD score.

Randomized Controlled Trial of Intravenous Ferric Carboxymaltose vs Oral Iron to Treat Iron Deficiency Anemia After Variceal Bleed in Patients With Cirrhosis.

INTRODUCTION: Limited evidence exists on the optimal strategy to correct iron deficiency anemia after variceal bleeding (VB) in cirrhosis. This trial compared the efficacy and safety of intravenous ferric carboxymaltose (IV-FCM) with those of oral iron therapy in this cohort. METHODS: In this open-label, single-center, randomized controlled trial, eligible patients with hemoglobin <10 g/dL and iron deficiency (ferritin <100 ng/mL) after VB received either IV-FCM (1,500-2,000 mg) divided into 2 doses (n = 48) or oral carbonyl iron (100 mg elemental iron/day) (n = 44) for 3 months. The primary outcome was change in hemoglobin at 3 months. Secondary outcomes included improvement in anemia (last hemoglobin >12 g/dL), normalization of iron stores (ferritin >100 ng/mL), liver-related adverse events, adverse drug reactions, and changes in quality of life (CLDQOL questionnaire). RESULTS: Baseline characteristics, including median Child-Turcotte-Pugh score 7 (interquartile range [IQR] 6-9), Model for End-Stage Liver Disease score 12 (IQR 10-17), blood hemoglobin (8.25 ± 1.06 g/dL), and ferritin (30.00 ng/mL [15.00-66.50]), were comparable in both arms. The median increase in hemoglobin at 3 months in the IV and oral arms was 3.65 g/dL (IQR 2.55-5.25) and 1.10 g/dL (IQR 0.05-2.90 g/dL) ( P < 0.001), respectively. Iron stores normalized in 84.6% and 21% of the IV and oral arms, respectively ( P < 0.001). Anemia improved in 50% and 21.9% in the IV and oral arms, respectively ( P < 0.009). Patients in the IV arm showed a significant improvement in all domains of CLDQOL. Liver-related adverse events were comparable in both arms. Transient mild/moderate hypophosphatemia developed in 43% of patients receiving IV-FCM. DISCUSSION: Intravenous iron replacement is efficacious and safe to treat iron deficiency anemia after VB in patients with cirrhosis.

Barriers at various levels of human ecosystem for maintaining adherence to gluten free diet in adult patients with celiac disease.

INTRODUCTION: While lifelong and strict adherence to gluten-free diet (GFD) is essential for the successful treatment of celiac disease (CeD), only 30-50% of patients are able to maintain a good adherence to GFD. We determined factors influencing the adherence to GFD at various ecological levels including intra-personal, inter-personal, organizational, community and system-based levels in adult patients with CeD. METHODS: A questionnaire to assess the adherence was developed and it was administered in the CeD clinic to patients with CeD on GFD for >1 year. Adherence to GFD was assessed in a subset of patients (n = 320) using Celiac Disease Adherence Test (CDAT). RESULTS: Overall, 978 patients [median age: 29 years; females: 592] with CeD on GFD were recruited. They reported many barriers to adherence to GFD including intra-personal barriers such as lack of knowledge about GFD (19%), inadequate financial resources (27.2%) and lack of self-motivation/confidence (55.3%); inter-personal barriers such as intake of gluten-containing food upon forceful insistence of friends/family (23.4%); organizational barriers such as high cost (70.8%) and non-availability of GF-food products (48.6%); community-based barriers like consumption of gluten-containing food at religious occasions/festivals (11.1%) and social occasions (27.2%); and system-based barriers such as non-referral to dietitian for counseling (21.9%). As per CDAT, 204 (63.7%), 73(22.8%) and 43(13.4%) patients had good, average, and poor adherence to GFD, respectively. On multivariable analysis, occasional consumption of gluten, non-availability of GF-food while dining out and coercing by family and friends for consumption of GC-food were found to have highest odds for poor adherence to GFD. CONCLUSIONS: Non-referral to a dietitian for counseling, irregular follow-up visits, unavailability of flour mill, non-supportive family/friends, high cost and limited availability of GF-food are the most common barriers to adherence to GFD. There is a need to create infrastructure and develop strategies to overcome these diverse barriers at various levels of ecosystem and thereby facilitate better adherence to GFD.

Opportunistic screening for osteopathy with routine abdominal computed tomography scan in chronic pancreatitis.

BACKGROUND AND AIMS: Lumbar vertebral bone attenuation, measured in Hounsfield units (HU) can indirectly indicate the bone mineral density (BMD). The aim of this study is to determine the optimal HU threshold on abdominal computed tomography (CT) scans to detect osteopathy in patients with chronic pancreatitis (CP). METHODS: This cross-sectional study included patients with CP who underwent CT scans to measure HU at L1 to L4 vertebrae. The mean lumbar vertebral attenuation of female renal transplant donors, aged 20-30 years was utilized to calculate the T-scoreHU of all patients at each vertebral level. Receiver operator characteristic analysis was used to determine the HU and T-scoreHU for diagnosis of osteopathy in patients with CP. Dual-energy X-ray absorptiometry value was used to categorize osteopenia and osteoporosis. RESULTS: A total of 175 patients (mean age, 34.5 ± 10.9 years; 72 % males) and 33 female renal transplant donors (mean age, 28 ± 2.4 years) were included. A threshold HU value 212 or T scoreHU of -1.80 at L1 vertebra was found to have a 78 % sensitivity and 70 % specificity for differentiating between osteoporosis and non-osteoporosis (osteopenia and normal BMD). Similarly, a threshold HU value of 254 or a T-scoreHU of -0.46 at L1 vertebra had 78 % sensitivity and 71 % specificity for distinguishing between normal and low BMD (osteoporosis and osteopenia). CONCLUSION: Abdominal CT images, which are routinely performed in chronic pancreatitis, can be used for opportunistic screening of osteoporosis and osteopenia without additional cost or radiation exposure.

Combination of Serum CA 19-9 and Endoscopic Ultrasound Findings Can Predict Malignancy Risk in Patients With Chronic Pancreatitis Presenting With Pancreatic Head Mass: A Proof-of-Concept Study.

BACKGROUND AND AIMS: Inflammatory head mass of pancreas (IMP) developing in background of chronic pancreatitis (CP) is difficult to distinguish from carcinoma pancreas. We aimed to delineate natural course of IMP and predict their malignancy risk, avoiding unnecessary biopsies. MATERIALS AND METHODS: In this retrospective single-center study, clinical records of patients with CP with diagnosed pancreatic head mass were reviewed. Clinical, laboratory, imaging, endoscopic findings, and follow-up details were retrieved from prospectively maintained database. A diagnostic nomogram was developed combining serum cancer antigen 19-9 and endoscopic ultrasound (EUS) findings to predict the risk of malignancy. RESULTS: We identified 107 patients with pancreatic head mass with CP of whom 87 (81.3%) were IMP and 20 (18.7%) were malignant. Patients with IMP were more frequently young males with alcohol-related CP and low CA 19-9 in comparison with those with malignancy (age IMP: 41.3 ± 11.3 vs carcinoma: 49.3 ± 14.5 years [ P = 0.009]; males 89.7% vs 65% [ P = 0.011]; alcoholic etiology: 71.3% vs 20% [ P < 0.001]; median CA 19-9: 25.78 [interquartile range, 7.20-120.60] vs 1034.50 [106.65-7808.25] [ P < 0.001]). A diagnostic nomogram combining CA 19-9 and EUS findings could identify malignancy with an optimism-corrected c-statistic of 0.905, which was better than both CA 19-9 (0.80) and EUS alone (0.826). Patients with IMP had relatively benign disease course with 40.2% biliary obstruction, 20.7% portal venous thrombosis, 14.9% gastric outlet obstruction, and 1-, 3-, and 5-year survival being 97.3%, 92.7%, and 92.0%, respectively. Surgery was required in only 12 patients (13.8%) with IMP. CONCLUSIONS: Combination of CA 19-9 and EUS best identifies malignancy risk in patients with IMP, who have otherwise benign course.

An Open-label Randomized Controlled Trial of Early Initiation of Nasogastric Feeding After Endotherapy in Variceal Bleeding: A Proof-of-concept Study.

Background and aims: Limited data exist on the safety of early nasogastric (NG) feeding in patients with cirrhosis after endotherapy for variceal bleeding (VB). We studied the impact of early NG tube feeding in these patients in this proof-of-concept open-label randomized controlled trial. Methods: Eligible patients with cirrhosis undergoing endotherapy for VB were randomized to receive either a liquid diet through a 14 Fr NG tube (commencing 1 h after endotherapy) (early feeding [EF] group) or sips of water and lemon water orally (standard-of-care [SOC] group) for total duration of 48 h. The primary outcome was 5-day rebleeding in both arms. Other outcomes included 5-day infection rate, hepatic encephalopathy during hospitalization, and 6-week mortality. Results: Eighty patients (Mean age: 41 ± 11.5 years; males [82.5%]; alcohol etiology [55%]) were included. Baseline median Child-Pugh and MELD scores were similar (CTP: 8 [IQR: 8-9] vs 9 [8-9.25]; P = 0.47 and MELDNa: 13 [10.75-16.25] vs 15 [12-18.25]; P = 0.16). The 5-day rebleeding rates in EF and SOC groups were 2.5% and 5%, respectively (P = 0.55), and non-inferiority or superiority of either could not be demonstrated. The incidence of infection (2.5% [EF] vs 2.5% [SOC]; P = 1.00) and development of HE (5% [EF] vs 2.5% [SOC]; P = 0.36) during hospitalization were comparable. The average daily calorie and protein intake in the EF group during the 48 h was 1318 ± 240 Kcals and 43.4 ± 9.2 g of proteins. No patient in the EF group had feed intolerance. Conclusion: Early initiation of NG tube-based feeding after endotherapy in VB appears safe and well tolerated without the additional risk of rebleeding or encephalopathy.

Utility of different Baveno criteria to detect esophageal varices irrespective of their size in patients with compensated cirrhosis.

BACKGROUND AND AIMS: Esophageal varices (EVs), irrespective of size, are the most-reliable indicators of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). While non-invasive tools (NITs) accurately identify those with varices needing treatment (VNTs), their role in identifying any EVs in patients with cACLD is not known. METHODS: Patients with cACLD with reliable liver stiffness measurements (LSM), blood parameters and gastroscopy were retrospectively recruited from a multinational cohort. The performance of Baveno-VI (LSM > 20kPa and platelet count < 150,000/mm3) and expanded Baveno-VI criteria (LSM > 25kPa or platelet count < 110,000/mm3) was assessed to detect VNTs as well as any EVs. This performance was compared with the Baveno-VII possible CSPH criteria (LSM ≥ 15 kPa and platelet ≤ 150,000/mm3) to evaluate its utility in detecting any EVs. RESULTS: Patients with cACLD (n = 1200) of predominantly viral etiology (hepatitis B virus, 269; hepatitis C virus, 564; non-alcoholic fatty liver disease, 145; alcoholic liver disease, 130; other, 92) were included. Any EVs and VNTs were present in 514 (42.8%) and 70 (5.8%) patients, respectively. The Baveno-VI, expanded Baveno-VI and Baveno-VII criteria missed 29/514 (5.6%), 115/514 (22.4%) and 19/514 (3.7%) patients with any EVs, respectively, whereas they misclassified 517/686 (75.4%), 211/686 (30.8%) and 598/686 (87.4%) patients with no EVs as having a high risk of EVs. The Baveno-VI, expanded Baveno-VI and possible CSPH criteria missed 3/70 (4.3%), 15/70 (21.4%) and 0/70 (0%) VNTs, respectively. CONCLUSION: Both original Baveno-VI and Baveno-VII criteria were highly sensitive in detecting varices in cACLD, albeit with high misclassification rates.

An LSM Based Strategy is Comparable to HVPG Measurement to Predict Further Events in Patients with Cirrhosis with Variceal Bleeding as Their Index Decompensation.

Background and aims: Limited data exist on strategies other than hepatic venous pressure gradient (HVPG) estimation to predict future events in patients with cirrhosis presenting with variceal bleed (VB) but are otherwise compensated. We assessed whether liver stiffness measurement (LSM) during VB episode could accurately predict this risk. Methods: Consecutive patients with cirrhosis with VB as their index decompensation event underwent HVPG and LSM estimation during the VB episode in this prospective study. New onset further decompensation events (ascites, VB, encephalopathy) was assessed over follow-up. The performance characteristics of postbleed LSM were compared with model for end stage liver disease (MELD) score and HVPG to predict future decompensation and were cross-validated. Results: Mean age of the cohort (n = 68) was 44.2 years and alcohol-related liver disease (55.9%) was the most common etiology. Over a median follow-up of 14 (9-18) months, 18(26.4%) patients developed further decompensation with ascites being the most common event. Patients with further decompensation had a higher median postbleed LSM [60.5 kPa (53-70) vs. 25 kPa (18-34), P < 0.001], HVPG [ 19 mm Hg vs. 16 mmHg, P = 0.005], and MELD score [ 12.5 (11-14.7) vs. 10 (8-12) P < 0.001]. The area under receiver-operator characteristics curve for postbleed LSM [0.928 (95%CI: 0.868-0.988)] was higher than both HVPG [0.733(0.601-0.865), P = 0.003] and MELD score [0.776(0.664-0.889), P = 0.019] to predict further decompensation. Optimism-corrected c-statistic using MELD and postbleed LSM was similar to a combination of HVPG, MELD, and postbleed LSM. Conclusion: Postbleed LSM is comparable to HVPG estimation in predicting further decompensation events in patients with otherwise compensated cirrhosis presenting with VB.

Universal prophylactic rectal nonsteroidal anti-inflammatory drugs with a policy of selective pancreatic duct stenting significantly reduce post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: Although rectal nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective for the prevention of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis (PEP) in high-risk patients, the benefit in average-risk patients is unclear. We aimed at assessing the benefit of prophylactic rectal NSAIDs in unselected consecutive patients to prevent PEP. METHODS: All patients undergoing index ERCP procedures from January 2018 until March 2020 were included. All patients received prophylactic rectal diclofenac. A prophylactic pancreatic duct (PD) stent was placed if there was repeated PD cannulation, at the discretion of the endoscopist. The frequency of PEP was compared with historical controls. RESULTS: Of 769 patients who underwent ERCP, 34 (4.4%) developed PEP (mild in 29 [85.3%], moderate in four [11.8%] and severe in one [2.9%]). Female gender, precut sphincterotomy, inadvertent PD cannulation and procedural time of > 30 minutes predicted PEP in univariate analysis. Inadvertent PD cannulation (OR 4.6, 95% CI: 1.8-11.7; p < 0.001) and procedural time of > 30 minutes (OR 8.5, 95% CI: 3.7-10.1; p < 0.001) were independent risk factors on multivariate analysis. When compared with historical controls, the odds of PEP with prophylactic use of rectal NSAIDs and selective PD stenting was 0.54 (CI: 0.31-0.93, p = 0.027). The number needed to treat (NNT) was 22 to prevent one PEP with prophylactic rectal NSAIDs. CONCLUSION: Routine use of prophylactic rectal NSAIDs effectively prevents the occurrence of PEP in unselected consecutive patients in a real-world scenario.

Revised Algorithmic Approach to Differentiate Between Nonspecific and Specific Etiologies of Chronic Terminal Ileitis.

INTRODUCTION: Chronic isolated terminal ileitis (TI) may be seen in Crohn's disease (CD) and intestinal tuberculosis (ITB) in addition to other etiologies that may be managed symptomatically. We developed a revised algorithm to distinguish patients with a specific etiology from a nonspecific etiology. METHODS: Patients with chronic isolated TI followed up from 2007 to 2022 were retrospectively reviewed. A specific (ITB or CD) diagnosis was made based on standardized criteria, and other relevant data were collected. Using this cohort, validation of a previously suggested algorithm was conducted. Furthermore, based on the results of a univariate analysis, a multivariate analysis with bootstrap validation was used to develop a revised algorithm. RESULTS: We included 153 patients (mean age 36.9 ± 14.6 years, males-70%, median duration-1.5 years, range: 0-20 years) with chronic isolated TI of whom 109 (71.2%) received a specific diagnosis (CD-69, ITB-40). On multivariate regression and validation statistics with a combination of clinical, laboratory, radiological, and colonoscopic findings, an optimism corrected c-statistic of 0.975 and 0.958 was obtained with and without histopathological findings, respectively. Revised algorithm, based on these, showed sensitivity, specificity, positive and negative predictive values, and overall accuracy of 98.2% (95% CI: 93.5-99.8), 75.0% (95% CI: 59.7-86.8), 90.7% (95% CI: 85.4-94.2), 94.3% (95% CI: 80.5-98.5) and 91.5%(95% CI:85.9-95.4), respectively. This was more sensitive and specific than the previous algorithm (accuracy 83.9%, sensitivity 95.5%, and specificity 54.6%). DISCUSSION: We developed a revised algorithm and a multimodality approach to stratify patients with chronic isolated TI into specific and nonspecific etiologies with an excellent diagnostic accuracy, which could potentially avoid missed diagnosis and unnecessary side effects of treatment.

Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure.

BACKGROUND AND AIMS: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment. METHODS: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks. RESULTS: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p < 0.001] to predict non-response. Combination of AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p < 0.001). CONCLUSION: Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

Utility of Fecal Elastase-1 to diagnose severe exocrine insufficiency in chronic pancreatitis: Real world experience.

INTRODUCTION: Quantitative fecal fat estimation is the gold standard test to diagnose steatorrhea (fecal fat >7 g/day) in chronic pancreatitis (CP), but cumbersome and inconvenient. So, fecal elastase-1 (FE) is proposed as a good alternative but the data on the diagnostic utility of FE to diagnose steatorrhea is variable. METHODS: This retrospective study included adult CP patients evaluated with both 24-h fecal-fat and FE tests within a 3-month period. The objective was to evaluate the diagnostic performance of FE to diagnose steatorrhea and to evaluate the FE progression over 9-month period. RESULTS: Among the 147 included patients, the frequency of steatorrhea (fecal fat >7 g/day) was 34%. The sensitivity, specificity, and negative likelihood ratio (LR) of FE was 90%, 28.9% and 0.35 at cut-off of <100 µg/g stool to diagnose steatorrhea; and 96%, 11.3% and 0.35 at cut-off of <200 µg/g stool, respectively. The optimal cut-off of FE was <20 on receiver operating characteristic curve (sensitivity 66%; specificity 69%; positive LR 2.14). There was no statistically significant variation in FE levels over 9 months interval among a hundred patients. CONCLUSION: Compared to FE ≥ 200 µg/g stool, FE ≥ 100 can used to exclude steatorrhea (better specificity and negative LR). FE < 20 alone cannot replace fecal fat estimation to confirm steatorrhea but to be interpreted with clinical features. Repeat FE testing for exocrine insufficiency progression can be done at least a year later.

Assessing the Risk of Further Decompensation and Survival in Patients With Cirrhosis With Variceal Bleeding as Their First Decompensation Event.

INTRODUCTION: Limited data exist on long-term outcomes of patients with compensated cirrhosis presenting with acute variceal bleeding (AVB) as an index and lone decompensating event. This study aimed to evaluate the incidence of further decompensation, survival, and risk factors of mortality in these patients. METHODS: Patients with otherwise compensated cirrhosis presenting with AVB as their index decompensating event (n = 463) were analyzed in this single-center retrospective study. The incidence of individual decompensation events and survival was estimated using competing risk analysis. Risk factors for poor outcomes were identified. RESULTS: The mean age was 47.4 (13.2) years, with most patients (86.5%) being males. Alcohol-related liver disease (42.3%) and viral cirrhosis (22.4%) were the main etiologies with a median Model for End-Stage Liver Disease score of 14 (11-15) at baseline. Over a median follow-up of 42 (24-62) months, 292 patients experienced further decompensations: ascites (n = 283; 96.9%), rebleeding (n = 157; 53.8%), and hepatic encephalopathy (n = 71; 24.3%). Most events occurred with similar frequency across different etiologies, except acute-on-chronic liver failure, which was more common in nonviral cirrhosis (Gray test, P = 0.042). Patients with viral and nonviral cirrhosis had similar survival (5-year survival: 91% and 80.1%, respectively; P = 0.062). Patients with early further decompensations (onset <6 weeks of index AVB event) (n = 40) had a higher mortality (52.5% vs 20.2% for late decompensations; P < 0.001). Active alcohol consumption (hazard ratio [HR]: 9 [5.31-15.3], P < 0.001), high white blood cell count at presentation (HR: 2.5 [1.4-4.4], P = 0.001), and early decompensation (HR: 6.2 [3.6-10.6], P < 0.001) predicted poor survival. DISCUSSION: Despite a high incidence of further decompensation, 5-year survival of patients at this stage of cirrhosis is more than 80% across all etiologies in the absence of early further decompensation and active alcohol consumption.

Chronic Pancreatitis in Females is Not Associated With Adverse Pregnancy Outcomes: A Retrospective Analysis.

BACKGROUND: The effects of chronic pancreatitis (CP) on pregnancy and vice versa have not been studied well. We aimed to study the impact of CP on pregnancy-related outcomes and the effect of pregnancy on clinical profile of CP. STUDY AND GOALS: We did a retrospective analysis of all female patients of CP of child-bearing age (above 18 y). The pregnancy-related outcomes of patients with CP were compared with the age-matched 115 controls from the low-risk pregnancy group identified using a simplified antepartum high-risk pregnancy scoring form. The clinical course of CP during pregnancy was compared with the pre-pregnancy course. RESULTS: Among the 338 eligible patients, 46 patients were included after exclusions. All these 46 patients had at least 1 conception and 41 had at least 1 completed pregnancy with a total of 117 conceptions and 96 completed pregnancies. The pregnancy-related outcomes in patients with CP like abortions (21.7% vs. 11.3%; P =0.087), preterm deliveries (14.6% vs. 10.4%; P =0.47), antepartum course (82.7% vs. 82.6%; P =0.58), stillbirths (4.9% vs. 4.3%; P =0.88), cesarean section (36.6% vs. 34%; P =0.849) were comparable with controls. There was overall improvement in the severity and frequency of pain during pregnancy as compared with the pre-pregnancy symptoms ( P =0.001). CONCLUSION: CP is not associated with adverse pregnancy outcomes. Also, there is trend toward improvement in the clinical symptoms because of CP during the pregnancy.

Distinct course of portal hypertension in patients with cirrhosis with gastric variceal bleeding as their first decompensation: a propensity score-matched study.

BACKGROUND AND AIMS: Limited data exist on course of portal hypertension in patients with cirrhosis with gastric variceal (GV) bleeding as their index decompensation. We evaluated long-term outcomes in this subgroup and compared them with a propensity score-matched cohort of patients with esophageal variceal (EV) bleeding. METHODS: Patients with cirrhosis with GVs (IGV-1 and GOV-2) bleeding as their index decompensation were analyzed in this retrospective study. Incidence of new-onset clinical decompensations and survival were estimated and compared with a cohort of patients with EVs bleeding matched for etiology and disease severity using competing risk analysis. RESULTS: Baseline characteristics of patients with GVs related bleeding (n = 51) (mean age-48.1 ± 12.9 years, 80% males, non-viral cirrhosis: 80.3%) were similar to the cohort of EVs bleeding (n = 51) (mean age-45.9 ± 14.2, 88% males, non-viral cirrhosis: 78.4%). The 1-year and 3-year rates of new-onset ascites were (17.9%, 34.2%) and (23.9%, 49%) in patients with GVs and EVs related index bleeding, respectively (Gray's test, p = 0.035). The 1-year and 3 year rate of rebleed was (35.6%, 46.3%) and (13.9%, 35.7%) in patients with GVs and EVs related index bleeding, respectively (Gray's test, p = 0.1). While overall survival was similar across both the groups (GV: 29.6% vs EV: 21.6%, p = 0.495), rebleeding-related deaths occurred exclusively in patients with GV (rebleeding-related deaths: GV: 40% vs EVs: 0%; non-bleeding liver-related deaths: GV: 60% vs EV: 100%; p = 0.048). CONCLUSIONS: Rebleeding predominates the course of portal hypertension in patients with cirrhosis presenting with GVs related bleeding, whereas ascites is the most significant event on follow-up in those with EVs related bleeding.

Acute pancreatitis is characterized by generalized intestinal barrier dysfunction in early stage.

BACKGROUND AND AIMS: The role of intestinal-barrier in acute pancreatitis(AP) is poorly understood. We aimed to assess structural and functional changes in the intestinal-barrier in patients with early AP (time from onset<2 weeks) and the effect of enteral nutrition on them. METHODS: In this prospective observational study, patients with early AP not on enteral nutrition were compared with controls for baseline intestinal-permeability(lactulose: mannitol ratio(L:M)), endotoxinemia(serum IgM/IgG anti-endotoxin antibodies), bacterial-translocation(serum bacterial 16S rRNA) and duodenal epithelial tight-junction structure by immunohistochemistry(IHC) for tight-junction proteins(claudin-2,-3,-4, zonula occludens-1(ZO1), junctional adhesion molecule(JAM) and occludin) and electron microscopy. These parameters were reassessed after 2 weeks enteral feeding in a AP patients subset. RESULTS: 96 patients with AP(age: 38.0 ± 14.5 years; etiology: biliary[46.8%]/alcohol[39.6%]; severe:53.2%, mortality:11.4%) and 40 matched controls were recruited. Patients with AP had higher baseline intestinal permeability(median L:M 0.176(IQR 0.073-0.376) vs 0.049(0.024-0.075) in controls; p < 0.001) and more frequent bacteraemia(positive bacterial 16S rRNA in 24/48 AP vs 0/21 controls; p < 0.001) with trend towards higher serum endotoxinemia(median IgG anti-endotoxin 78(51.2-171.6) GMU/ml vs 51.2(26.16-79.2) in controls; p = 0.061). Claudin-2, claudin-3, ZO1 were downregulated in both duodenal crypts and villi while claudin-4 and JAM were downregulated in duodenal villi and crypts respectively. 22 AP patients reassessed after initiation of enteral nutrition showed trend towards improving intestinal permeability, serum endotoxinemia and bacteraemia, with significant improvement in claudin-2,-3 in duodenal villi. CONCLUSION: Patients with AP have significant disturbances in intestinal barrier structure and function in first 2 weeks from onset that persist despite institution of enteral nutrition.