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.

Natural course of chronic pancreatitis and predictors of its progression.

BACKGROUND: The natural course of chronic pancreatitis(CP) and its complications has been inadequately explored. We aimed to describe the natural history and factors affecting the progression of alcoholic(ACP), idiopathic juvenile(IJCP) and idiopathic senile(ISCP) variants of CP. METHODS: This study was a retrospective analysis from a prospectively maintained database of patients with CP following up at a tertiary care centre from 1998 to 2019. Cumulative rates of pain resolution, diabetes, steatorrhea, pseudocysts and pancreatic cancer were computed using Kaplan-Meier analysis, and the factors affecting their incidence were identified on multivariable-adjusted Cox-proportional-hazards model. RESULTS: A total of 1415 patients were included, with 540(38.1%) ACP, 668(47.2%) IJCP and 207(14.6%) ISCP with a median follow-up of 3.5 years(Inter-quartile range: 1.5-7.5 years). Diabetes occurred at 11.5, 28 and 5.8 years(p < 0.001) while steatorrhea occurred at 16, 24 and 18 years(p = 0.004) after onset for ACP, IJCP and ISCP respectively. Local complications including pseudocysts occurred predominantly in ACP(p < 0.001). Ten-year risk of pancreatic cancer was 0.9%, 0.2% and 5.2% in ACP, IJCP and ISCP, respectively(p < 0.001). Pain resolution occurred more frequently in patients with older age of onset[Multivariate Hazard Ratio(HR):1.7(95%CI:1.4-2.0; p < 0.001)], non-smokers[HR:0.51(95%CI:0.34-0.78); p = 0.002] and in non-calcific CP[HR:0.81(0.66-1.0); p = 0.047]. Occurrence of steatorrhea[HR:1.3(1.03-1.7); p = 0.028] and diabetes[HR:2.7(2.2-3.4); p < 0.001] depended primarily on age at onset. Occurrence of pancreatic cancer depended on age at onset[HR:12.1(4.7-31.2); p < 0.001], smoking-history[HR:6.5(2.2-19.0); p < 0.001] and non-alcoholic etiology[HR:0.14(0.05-0.4); p < 0.001]. CONCLUSION: ACP, IJCP and ISCP represent distinct entities with different natural course. Age at onset of CP plays a major prognostic role in all manifestations, with alcohol predominantly causing local inflammatory complications.

Basics and Art of Immunosuppression in Liver Transplantation.

Liver transplantation is one of the most challenging areas in the medical field. Despite that, it has already been established as a standard treatment option, especially in decompensated cirrhosis and selected cases of hepatocellular carcinoma and acute liver failure. Complications due to graft rejection, including mortality and morbidity, have greatly improved over time due to better immunosuppressive agents and management protocols. Currently, immunosuppression in liver transplant patients makes use of the best possible combinations of effective agents to achieve optimal immunosuppression for long-term graft survival. Induction agents are no longer used routinely, and the aim is to provide minimal immunosuppression in the maintenance phase. Currently available immunosuppressive agents are mainly classified as biological and pharmacological agents. Though the protocols may vary among the centers and over time, the basics of effective use usually remain similar. Most protocols use the combination of multiple agents with different mechanisms of action to reduce the dose and minimize the side effects. Along with the improvement in operative and perioperative techniques, this art of immunosuppression has contributed to the recent progress made in the outcomes of liver transplants. In this review, we will discuss the various types of immunosuppressive agents currently in use, the different protocols of immunosuppression used, and the art of optimal use for achieving maximum immunosuppression without increasing toxicity. We will also discuss the practical aspects of various immunosuppression regimens, including drug monitoring, and briefly discuss the concepts of immunosuppression minimization and withdrawal.

Liver injury at admission and outcomes in patients with COVID-19 disease: a prospective cohort study.

The liver is one of the common extrapulmonary organs involved in the coronavirus disease 2019 (COVID-19) infection. We aimed to find the prevalence of liver injury at hospital admission and its effects on outcomes. Methods: This is a single-center prospective observational study. All consecutive patients with COVID-19 admitted during the months of May to August 2021 were included in the study. Liver injury was defined as at least 2 times elevation of aspartate transaminase, alanine transaminase, alkaline phosphatase, and bilirubin above the upper limits on normal. The predictive efficacy of liver injury was measured as its effects on outcome variables, that is duration of hospital stay, requirement of ICU admission, mechanical ventilation, and mortality. Presence of liver injury compared with existing biomarkers markers of severe disease, that is lactate dehydrogenase, D-dimer, and C-reactive protein. Results: A total of 245 consecutive adult patients with COVID-19 infection were included in the study. Liver injury was present in 102 (41.63%) of patients. There was a significant association between the presence of liver injury and duration of hospital stay (10.74 vs. 8.9 days; P=0.013), the requirement of ICU admission (12.7 vs. 10.2%; P=0.018), mechanical ventilation (10.6% vs. 6.5%; P=0.003), and mortality (13.1% vs. 6.1%; P<0.001). Liver injury was significantly associated (P<0.001) with the corresponding elevation of serum biomarkers of severity. Conclusion: The presence of liver injury in patients with COVID-19 infection at the time of hospital admission is the independent predictor of poor outcomes and can also be used as the marker of disease severity.

Chronic Liver Disease among Patients Admitted in the Department of Internal Medicine of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Chronic liver disease with cirrhosis is a significant cause of morbidity and mortality not only in developed but also in developing countries. Many patients already develop complications before hospital admission and require intensive medical care during hospital treatment. The main objective of the study was to find out the prevalence of the chronic liver disease among patients admitted in the Department of Internal Medicine of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among patients admitted to the Department of Internal Medicine of a tertiary care centre from 1 January 2022 to 31 March 2022. Ethical approval was obtained from the Ethical Review Board (Reference number: 2211202105). The patient admitted in the Department during the study period was included and those who do not gave consent were excluded. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Out of 447 patients, the prevalence of chronic liver disease was 93 (20.8%) (17.04-24.56, 95% Confidence Interval). The mean age of the patients was 49.69±10.94 years and among them, males were 64 (68.82%). Conclusions: The prevalence of the chronic liver disease among patients admitted to the Department of Internal Medicine of a tertiary care centre was lower than in other studies conducted in similar settings. Keywords: alcoholic liver diseases; liver diseases; prevalence.

Eosinophilic gastritis without peripheral eosinophilia and atopy: A case report.

Eosinophilic gastritis (EG) is characterized by eosinophilic infiltration of any gastric layers. We report a 65-year-female presenting with abdominal pain and vomiting for two months. Chronic gastritis not responding to empirical treatment interrogated further investigations. In the absence of atopy and peripheral eosinophilia, successful treatment of a large solitary antral ulcer with steroids upheld the diagnosis of EG.

Esophageal Actinomycosis in an Immunocompetent Patient Mimicking Carcinoma: A Case Report.

Esophageal actinomycosis is a rare occurrence that presents a diagnostic challenge due to its vague clinical picture. The common symptoms include dysphagia, odynophagia and epigastric pain. These symptoms, although alarming, are usually non-specific. In this report, we describe an immunocompetent 38-year-old woman who presented with dysphagia and burning chest pain. Her initial examination and investigations suggested carcinoma of the oesophagus. On further evaluation and histopathology examination, she was diagnosed with esophageal actinomycosis and managed with antibiotics and symptomatic relief. She had significant improvement on follow up examination. The diagnosis of this condition in an immunocompetent patient can be confusing and requires a high degree of suspicion. Keywords: actinomycosis; carcinoma; case reports; esophagus.

Demonstration of Gut-Barrier Dysfunction in Early Stages of Non-alcoholic Fatty Liver Disease: A Proof-Of-Concept Study.

Background/Aims: Gut-barrier dysfunction is well recognized in pathogenesis of both non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). However, comparison of components of this dysfunction between the two etiologies remains unexplored especially in early stages of NAFLD. Methods: Components of gut-barrier dysfunction like alterations in intestinal permeability (IP) by lactulose mannitol ratio (LMR) in urine, systemic endotoxemia (IgG and IgM anti-endotoxin antibodies), systemic inflammation (serum tumor necrosis factor alpha [TNF-α] and interleukin-1 [IL-1] levels), tight junction (TJ) proteins expression in duodenal biopsy and stool microbiota composition using Oxford Nanopore MinION device were prospectively evaluated in patients with NAFLD (n = 34) with no cirrhosis, ALD (n = 28) and were compared with disease free controls (n = 20). Results: Patients with ALD had more advanced disease than those with NAFLD (median liver stiffness -NAFLD:7.1 kPa [5.9-8.9] vs. ALD:14.3 kPa [9.6-24], P < 0.001]. Median LMR was significantly higher in NAFLD and ALD group when compared to controls (NAFLD 0.054 [0.037-0.17] vs. controls 0.027 [0.021-0.045] (P = 0.001)) and ALD 0.043 [0.03-0.068] vs. controls 0.027 [0.021-0.045] (P = 0.019)]. Anti-endotoxin antibody titer (IgM) (MMU/mL) was lowest in NAFLD 72.9 [3.2-1089.5] compared to ALD 120.6 [20.1-728]) (P = 0.042) and controls 155.3 [23.8-442.9]) (P = 0.021). Median TNF-α (pg/mL) levels were elevated in patients with NAFLD (53.3 [24.5-115]) compared to controls (16.1 [10.8-33.3]) (P < 0.001) and ALD (12.3 [10.1-42.7]) (P < 0.001). Expression of zonulin-1 and claudin-3 in duodenal mucosa was lowest in NAFLD. On principal co-ordinate analysis (PCoA), the global bacterial composition was significantly different across the three groups (PERMANOVA test, P < 0.001). Conclusion: While remaining activated in both etiologies, gut-barrier dysfunction abnormalities were more pronounced in NAFLD at early stages compared to ALD despite more advanced disease in the latter.