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Background Prednisolone is considered the cornerstone treatment for severe alcoholic hepatitis (AH). However, its use is limited by the increased risk of infection in an already immunocompromised patient population. Among patients with severe AH, there exists a group of non-responders who do not benefit from prednisolone therapy. Day-4 Lille score is a widely employed prognostic model used to identify this non-responder subgroup. The present study evaluates the prognostic ability of the inflammatory marker, the neutrophil-lymphocyte ratio (NLR), as a stand-alone model and in conjunction with the day-4 Lille score. Methods We retrospectively reviewed the electronic medical records of patients diagnosed with AH. Demographic and biochemical data at diagnosis were collected to calculate Maddrey's discriminant function (MDF) and model for end-stage liver disease (MELD) score upon admission and also on day 4. Receiver operating characteristic (ROC) curves were plotted for day-4 NLR and day-4 Lille score for prediction of 90-day mortality, and optimal cut-off values were determined. Patients were then subcategorized into groups based on the generated optimal cut-off values. Categorization was validated by comparing the mortality rate in each group with the chi-squared test. We then performed a multivariate analysis for prediction of 90-day mortality using day-4 Lille score and day-4 NLR, constructing a new prediction score based on the odds ratio (OR). The ROC curve of the new score was plotted and the area under a curve (AUC) was reported and compared with previously validated scores. Results Our analysis demonstrated that both day-4 NLR and Lille score individually predicted 90-day mortality with statistical significance (p: 0.049, p: <0.001, respectively). The ROC analysis of day-4 Lille score for the prediction of 90-day mortality revealed an AUC of 0.819 with an optimal cut-off value of 0.45 (sensitivity: 83.3%, specificity: 76.1%). Day-4 NLR had an AUC of 0.756 with an optimal cut-off value of 12.3 (sensitivity: 66.7%, specificity: 78.1%) The combined day-Lille-NLR model with a cut-off of 0.55 had an AUC of .889, which was higher than day-4 Lille score and NLR independently. Conclusion Day-4 NLR is an easily assessed prognostic model of mortality in alcoholic hepatitis. However, it often underperforms relative to day-4 Lille score. Combining these two models to create a "modified" Lille score adds increased performance characteristics to the prediction of outcomes/mortality. The "modified" Lille score presented in this study can be used to further cut down the number of non-responders who are often forced to undergo costly and potentially harmful treatment courses.
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Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have evaluated the efficacy of infliximab in such patients; however, they were limited by sample size. Our aim was to perform a systematic review of these studies to assess the role of infliximab in patients with SAH. We conducted a literature search using electronic database engines including Ovid, PubMed, Scopus, MEDLINE and Cochrane Library from inception to October 2018 to identify published articles addressing outcomes in patients treated for alcoholic hepatitis with infliximab. The primary outcome reviewed was one-month mortality. Secondary outcomes included rate and type of infection; cause of mortality; levels of aspartate aminotransferase, alanine aminotransferase, bilirubin and tumor necrosis factor-α; and Maddrey discriminant function. Five studies including two randomized controlled trials and three case series were included in our analysis with a total sample size of 70 patients. One-month mortality ranged from 10% to 17% in patients who received a single dose of infliximab with or without prednisone compared to 38% in patients who received three doses of infliximab in combination with prednisone. A single dose of infliximab was associated with an infection rate of 10% to 26% in contrast to an 89% rate with three doses of infliximab. Infliximab, when used in a single dose, could potentially be an alternative agent for the management of SAH in a large group of patients who have contraindications such as gastrointestinal bleeding, uncontrolled diabetes or an active hepatitis infection. It might also have a role in the prevention of hepatorenal syndrome. There is a need for larger trials to evaluate the role of infliximab in a cohort of patients who are not candidates for prednisolone therapy.
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Paraneoplastic gastrointestinal syndromes rarely precede the actual detection of an overt cancer with gastroparesis being a very rare initial presentation. To increase the clinical awareness of this rare clinical entity, we present a case of severe gastroparesis that was later proven to be associated with an occult poorly differentiated non-small cell lung cancer. We then continue to briefly review the relevant literature on paraneoplastic gastrointestinal syndromes to date. A 61-year-old African-American man presented with two months history of severe post-prandial nausea, vomiting and bloating associated with unintentional weight loss of 20 pounds. General physical examination revealed cachexia, temporal muscle wasting and clubbing of nails in both hands. The following investigations were normal or negative: basic metabolic panel, liver function tests, chest X-ray and esophagogastroduodenoscopy. Computed tomography (CT) scan of the abdomen showed residual food in the stomach and scintigraphic gastric emptying studies were consistent with gastroparesis. CT scan of the chest was performed which revealed a spiculated nodule sized 9 mm in right upper lobe of the lung with right hilar lymphadenopathy. Positron emission tomography (PET) scan revealed hyper-metabolic activity in the right upper lobe nodule and right hilar adenopathy. Nodule resection and biopsy revealed a poorly differentiated non-small cell lung carcinoma. Due to the concern of paraneoplastic origin of his gastroparesis further serological testing showed positive anti-neuronal nuclear antibodies type 1 (Anti-Hu) and cytoplasmic purkinje cell antibodies (Anti-Yo). The patient was started on a chemotherapy combination of Carboplatin and Paclitaxel with a three-week course of local radiation therapy. Moreover, for the relief of his severe gastrointestinal (GI) symptoms dietary modifications, pro-kinetic agents and psychological counseling were used with gradual clinical improvement observed on follow-up visits.
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Hepatic hydrothorax (HH) is an infrequent but debilitating and therapeutically challenging complication of advanced liver cirrhosis. As evidence suggests against chest tube placement in HH, many clinicians are reluctant to place indwelling pleural catheters (IPCs) for non-malignant effusions like HH. We aim to study the efficacy and safety of IPCs as an alternative treatment option in our systematic review. A literature search was conducted using the electronic database engines MEDLINE, PubMed, EMBASE, Ovid, Scopus and Cochrane Library (Cochrane Central Register of Controlled trials and Cochrane Database of Systematic Reviews) from inception to April 2018 to identify published articles and reports addressing outcomes in patients treated for HH with IPCs. The risk of bias was rated for each study using the Cochrane criteria. The search strategy retrieved 370 papers, of which four case series were selected with a total of 111 patients. After the insertion of IPCs for HH, spontaneous pleurodesis was achieved in 16 (31.4%) out of 51 patients at a mean duration of 73-222 days. As far as secondary outcomes were concerned, the frequency of pneumothorax during or after the procedure was 0 (0%) out of 92 patients, pain at insertion site 12 (20%) out of 60 patients, catheter blockage two (2.9%) out of 68 patients, pleural fluid infection five (4.5%) out of 111 patients and catheter-site cellulitis one (3.1%) out of 32 patients. Re-accumulation of pleural fluid after catheter removal was mentioned in one study, wherein 12 (20%) out of 60 patients developed recurrence of pleural effusion. We conclude IPCs as an acceptable therapeutic option for the management of refractory pleural effusion in patients with HH. Although trans-jugular intrahepatic portosystemic shunt (TIPS) and liver transplantation are the gold standards for the management of pleural effusion in these patients, cost and availability are the major concerns with these treatment modalities. IPCs are a safe and efficacious alternative with a reasonable rate of spontaneous pleurodesis.
