Post-acute pancreatitis diabetes: A complication waiting for more recognition and understanding.

Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.

Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives.

Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.

Diagnostic and therapeutic challenges of gastrointestinal angiodysplasias: A critical review and view points.

Gastrointestinal angiodysplasias (GIADs), also called angioectasias, are the most frequent vascular lesions. Its precise prevalence is unknown since most of them are asymptomatic. However, the incidence may be increasing since GIADs affect individuals aged more than 60 years and population life expectancy is globally increasing worldwide. They are responsible of about 5% to 10% of all gastrointestinal bleeding (GIB) cases. Most GIADs are placed in small bowel, where are the cause of 50 to 60% of obscure GIB diagnosed with video capsule endoscopy. They may be the cause of fatal severe bleeding episodes; nevertheless, recurrent overt or occult bleeding episodes requiring repeated expensive treatments and disturbing patient's quality-of-life are more frequently observed. Diagnosis and treatment of GIADs (particularly those placed in small bowel) are a great challenge due to insidious disease behavior, inaccessibility to affected sites and limitations of available diagnostic procedures. Hemorrhagic causality out of the actively bleeding lesions detected by diagnostic procedures may be difficult to establish. No treatment guidelines are currently available, so there is a high variability in the management of these patients. In this review, the epidemiology and pathophysiology of GIADs and the status in the diagnosis and treatment, with special emphasis on small bowel angiodysplasias based on multiple publications, are critically discussed. In addition, a classification of GIADs based on their endoscopic characteristics is proposed. Finally, some aspects that need to be clarified in future research studies are highlighted.

Low Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Patients with Esophageal Food Impaction in Mexican Population.

BACKGROUND: Eosinophilic esophagitis (EoE) is the most common cause of dysphagia and esophageal food impaction (EFI) in the USA, Western Europe, and Australia. In Mexico, the uncomplicated form of this disease is infrequent, and prevalence in patients with EFI is unknown. AIMS: To determine the prevalence and causes of EFI, endoscopic and therapeutic aspects, and establish the prevalence of biopsy-proven EoE in patients with EFI. METHODS: Diagnostic upper gastrointestinal endoscopy reports from January 2011 to December 2016 were retrospectively reviewed. Patients with therapeutic procedures, gastrointestinal hemorrhage, or non-food foreign body impaction were excluded. The number of patients with EFI was determined. Additionally, patients with esophageal biopsy were retained for EoE prevalence calculation. The diagnosis of EoE was defined with the presence of eosinophil infiltration count ≥ 15/high-power field with or without typical endoscopic abnormalities. RESULTS: A total of 4700 reports of the same number of patients were selected; 2209 were males (47%) with a mean age of 57.6 ± 12.3 years (range 14-93). We identified 36 patients with EFI (0.76, 95% CI 0.51-1.01), 16 males (44.4%) with a mean age of 54.9 ± 19.7 (range 22-92). Esophageal biopsies were obtained in 17/36 (47.2%) cases. The diagnosis of EoE was confirmed in 2 patients (11.7%). Peptic stenosis was the most frequent cause of EFI. CONCLUSIONS: EoE is an infrequent cause of EFI in the Mexican population (11.7%). EoE had the lowest prevalence compared to that reported in Caucasian populations. The prevalence of EFI was also low.

Acute Variceal Bleeding: Does Octreotide Improve Outcomes in Patients with Different Functional Hepatic Reserve?

BACKGROUND: Current guidelines do not differentiate in the utilization of vasoactive drugs in patients with cirrhosis and acute variceal bleeding (AVB) depending on liver disease severity. MATERIAL AND METHODS: In this retrospective study, clinical outcomes in 100 patients receiving octreotide plus endoscopic therapy (ET) and 216 patients with ET alone were compared in terms of failure to control bleeding, in-hospital mortality, and transfusion requirements stratifying the results according to liver disease severity by Child-Pugh (CP) score and MELD. RESULTS: In patients with CP-A or those with MELD < 10 octreotide was not associated with a better outcome compared to ET alone in terms of hospital mortality (CP-A: 0.0 vs. 0.0%; MELD < 10: 0.0 vs. 2.9%, p = 1.00), failure to control bleeding (CP-A: 8.7 vs. 3.7%, p = 0.58; MELD < 10: 5.3 vs. 4.3%, p = 1.00) and need for transfusion (CP-A: 39.1 vs. 61.1%, p = 0.09; MELD < 10: 63.2 vs. 62.9%, p = 1.00). Those with severe liver dysfunction in the octreotide group showed better outcomes compared to the non-octreotide group in terms of hospital mortality (CP-B/C: 3.9 vs. 13.0%, p = 0.04; MELD ≥ 10: 3.9 vs. 13.3%, p = 0.03) and need for transfusion (CP-B/C: 58.4 vs. 71.6%, p = 0.05; MELD ≥ 10: 50.6 vs. 72.7%, p < 0.01). In multivariate analysis, octreotide was independently associated with in-hospital mortality (p = 0.028) and need for transfusion (p = 0.008) only in patients with severe liver dysfunction (CP-B/C or MELD ≥ 10). CONCLUSION: Patients with cirrhosis and AVB categorized as CP-A or MELD < 10 had similar clinical outcomes during hospitalization whether or not they received octreotide.

Nonvariceal upper gastrointestinal bleeding in elderly people: Clinical outcomes and prognostic factors.

OBJECTIVE: To analyze the clinical characteristics, outcomes and prognostic factors in elderly patients (aged 75 years and elder) with acute nonvariceal upper gastrointestinal bleeding (UGIB). METHODS: Consecutive patients admitted with acute nonvariceal UGIB who underwent upper gastrointestinal endoscopy were prospectively recruited and subdivided into two age-based groups, elderly (aged ≥75 years) and younger patients (<75 years). The patients' characteristics and outcomes were recorded. RESULTS: Altogether 1136 patients were included in the study, 276 (24.3%) aged ≥75 years. Peptic ulcers, gastroduodenal erosions and esophagitis represented the three most common endoscopic lesions found in 87.7% of the elderly patients compared with 80.8% in younger patients ( P = 0.008). Overall, the rebleeding rate (4.0% vs 3.3%, P = 0.568), need for blood transfusion (66.3% vs 61.0%, P = 0.122), surgery rate (1.2% vs 1.4%, P = 0.947) and in-hospital mortality (13.0% vs 10.0%, P = 0.157) were not different between the two groups. In elderly patients, serum albumin was the only predictive variable independently associated with mortality in the overall analysis (OR 5.867, 95% CI 2.206-15.604, P < 0.001) and in the subgroup patients with peptic ulcers (OR 5.230, 95% CI 2.099-13.029, P = 0.001). Elderly patients with serum albumin >23.5 g/L at admission presented a low mortality (negative predictive value 97.3%). CONCLUSIONS: Clinical evolution and mortality do not differ between the elderly and younger patients with acute nonvariceal UGIB. Serum albumin level at admission is a prognostic marker for mortality in elder patients.

Portal vein thrombosis in patients with cirrhosis: just a common finding or a predictor of poor outcome?

 Background & Aims. It is unclear whether portal vein thrombosis (PVT) unrelated to malignancy is associated with reduced survival or it is an epiphenomenon of advanced cirrhosis. The objective of this study was to assess clinical outcome in cirrhotic patients with PVT not associated with malignancy and determine its prevalence. MATERIAL AND METHODS: Retrospective search in one center from June 2011 to December 2014. RESULTS: 169 patients, 55 women and 114 men, median age 54 (19-90) years. Thirteen had PVT (7.6%). None of the patients received anticoagulant treatment. The PVT group was younger (49 [25-62] vs. 55 [19-90] years p = 0.025). Child A patients were more frequent in PVT and Child C in Non-PVT. Median Model for End Stage Liver Disease (MELD) score was lower in PVT (12 [8-21] vs. 19 [7-51] p ≤ 0.001) p ≤ 0.001). There was no difference between upper gastrointestinal bleeding and spontaneous bacterial peritonitis in the groups. Encephalopathy grade 3-4 (4 [30.8%] vs. 73 [46.8%] p = 0,007) and large volume ascites (5 [38.5%] vs. 89 [57.1%] p= 0,012) was more common in non-PVT. Survival was better for PVT (16.5 ± 27.9 vs. 4.13 ± 12.2 months p = 0.005). CONCLUSIONS: We found that PVT itself does not lead to a worse prognosis. The most reliable predictor for clinical outcome remains the MELD score. The presence of PVT could be just an epiphenomenon and not a marker of advanced cirrhosis.

Primary biliary cholangitis associated with warm autoimmune hemolytic anemia.

There are many autoimmune diseases associated with primary biliary cholangitis (PBC), known as primary biliary cirrhosis; however, the association between PBC and warm autoimmune hemolytic anemia (wAIHA) has rarely been reported. It is documented that hemolysis is present in over 50% of the patients with chronic liver disease, regardless of the etiologies. Due to the clear and frequent relationship between PBC and many autoimmune diseases, it is reasonable to suppose that wAIHA may be another autoimmune disorder seen in association with PBC. Here we reported a 53-year-old female patient diagnosed with wAIHA associated with PBC.

The treatment of diabetes mellitus of patients with chronic liver disease.

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.

Hypertriglyceridemia-induced pancreatitis and risk of persistent systemic inflammatory response syndrome.

BACKGROUND: The mechanisms responsible for the development of acute pancreatitis (AP) and its complications are not fully understood. AIM: To assess the role of clinical and host molecular factors for the development and outcome of persistent systemic inflammatory response syndrome (SIRS) in patients with AP. METHODS: We included 191 patients with AP in the study. The considered variables were demographic characteristics, prognosis and outcome, etiology, laboratory findings and complications. Interleukin (IL) 10 (-1082 G/A, -592 C/A), TNFA-308 (G/A) and ILB-31 (C/T) polymorphisms were determined by pyrosequencing. An amplification refractory mutation system-polymerase chain reaction method was used to genotype the IL8-251 (A/T) polymorphism. RESULTS: Demographic characteristics were not statistically significant risk factors for the acquisition of persistent SIRS in patients with AP. Patients with hypertriglyceridemia were more likely to develop persistent SIRS (P < 0.05). No association with the TNFA, ILB, IL8-251 (A/T) and IL10 single-nucleotide polymorphisms was detected from the allele, genotype or haplotype frequencies. CONCLUSIONS: Patients with hypertriglyceridemia-induced AP were more likely to develop persistent SIRS.

Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study.

AIMS: To define if there is an imbalance in plasma levels of proinflammatory, fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and impaired glucose tolerance (IGT) or diabetes mellitus (DM). MATERIAL AND METHODS: We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma levels of cytokines were measured: TNF- α, soluble tumor necrosis factor receptor 1 (sTNF-R1), leptin, TGF-ß1, and hepatocyte growth factor (HGF). Also, fasting plasma insulin (FPI) levels were determined and HOMA2-IR was calculated. Results were compared with those of a control group of 18 patients without liver disease nor DM. Intergroup comparison was performed using non parametric tests. RESULTS: Significantly higher sTNF-R1 and lower TGF-ß1 were found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF-α levels showed no significant differences. According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found. CONCLUSIONS: IGT and DM were associated with abnormalities of sTNF-R1 and TGF-ß1 compared to non cirrhotic controls. Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease. Finally, sTNF-R1 and leptin correlated with IR. These findings suggest that IGT and DM may be causally implicated with liver inflammation process.

Value of clinical criteria to indicate a CT-FNA in the diagnosis of infected acute pancreatitis.

OBJECTIVE: To assess the value of clinical criteria in detecting pancreatic infection (PI) on or after the seventh day of acute pancreatitis attack (AP). METHODS: We determined as clinical criteria of suspicion of PI (SPI): the presence, persistence or recurrence of fever > or = 38 degrees C, leukocytosis > or = 12,000/mm3 and organ failure (OF) in the absence of extrapancreatic infection. Patients with SPI criteria underwent computed tomography - fine needle aspiration (CT-FNA), if CT-FNA was negative and SPI criteria for 72 hours CT-FNA was repeated. RESULTS: We prospectively studied 369 patients with AP and found 48 patients who met SPI criteria (mean age 37 yr, 17-70 yr), 30 male and 18 female. Etiology was biliary (56.2%), alcohol (35.4%) and others (8.4%). We performed 53 CT-FNA in 48 patients and 28 were diagnosed with PI. At the time of CT-FNA 50% of patients had OF. Mean time for CT-FNA in patients with PI was 12.5 +/- 7 days. Mean clinical followup after hospital discharge was one month. No patients with SPI criteria and negative CT-FNA or patients without SPI criteria developed clinical signs of PI. The SPI criteria had a sensitivity of 100%, specificity of 94% (CI 95% 92-97), PPV of 58% (IC 95% 44-72) and NPV of 100%. CONCLUSIONS: The application of SPI criteria on or after the seventh day of onset of AP can be a useful tool in making the decision and defining the time to perform a CT-FNA in order to clarify the clinical scenario between SIRS and sepsis related PI. Our approach can lead to better strategic treatments in the management of these difficult cases.