Purpose: Functional heart burn is a challenging clinical entity. Rome III criteria confirmed the clinical state. The subjects of collective, nonerosive reflux disease (NERD) with negative diagnostic studies, including histopathology and lower esophageal sphincter dysfunction, fall into the category of Functional Heart Burn (FHB) after a proton pump inhibition (PPI) challenge test. Therapeutic modalities are not yet established. Melatonin, a natural neurohormone related to serotonin, inhibits gastric acid secretion, alters nitric oxide function at gastroesophageal junction, and helps heal esophageal erosions. This study evaluates the possible role of melatonin in FHB.Methods: Sixty patients (n=60), ages 21-42 years (mean of 33), with Rome III proven FHB, were randomized into three groups. All patients underwent initial PPI challenge for 4 weeks, followed by panendoscopy with biopsies of antrum, body, distal and proximal esophagus. H. pylori, eosinophilic esophagitis (EoE) and mast cells were evaluated. All patients underwent pH monitoring (RESTEC pH monitoring). Group A (n=20) placebo at bedtime, Group B (n=20) Nortryptaline 25 mg orally at bed time, and Group C (n=20) over-the-counter(OTC)melatonin 6 mg at bed time for 3 months. All groups received omperazole 20 mg before breakfast and also underwent lifestyle modification. Pre- and post GERD-HQRL scores were analyzed. Exclusion: active ulcers, EOE, achalasia, esophageal stricture, infections of esophagus, scleroderma, H. pylori gastritis, and drugs affecting motility. Results: Patients in Melatonin group had a significantly higher percentage of relief (15/20=75%; Pearson's Chi-square=12.2, p=0.002) in heart burn score than those in Nortryptaline (4/20=20%) and Placebo (9/20=45%) groups. Melatonin group also had relatively better quality of life, less day time somnolence, and better tolerability compared to the other two groups. Side Effects: Melatonin- 5(25%)distension, 4(20%) diarrhea, and 4(20%) day time somnolence; Nortryptiline- 7(35%) constipation, 9(45%) somnolence, 11(55%) dry mouth, and 2(10%) dizziness; Placebo- 5(25%) constipation, 11(55%) daytime somnolence, and 6(30%) abdominal distension. Conclusion: OTC Melatonin improves functional heart burn and GERDHQRL score, is generally well tolerated, and offers a significant cost benefit. A larger trial is needed to validate.
Purpose: Interferon alpha (IFN-α) has been the mainstay of therapy for chronic hepatitis C. Side events of IFN-based therapy include autoimmune thyroiditis (10.7%). The effects of IFN gamma on calcium homeostasis have been well documented. Impacts of IFN-α on osteoclasts have been postulated. This study evaluated IFN-α induced autoimmune hyperparathyroidism, with or without eucalcemic state. Methods: 96 patients were evaluated, 45/90 patients treated with Pegylated IFN-α for chronic hepatitis C (group A- 75% alfa-2a, and 25% on alfa-2b), 36 patients with chronic hepatitis B (group B- 100% alfa-2a). 15 patients with multiple sclerosis (MS) (group C) treated with IFN beta for MS were recruited. Baseline and 24-week ionized calcium, serum parathyroid hormone intact (PTH intact), 24-hour urine calcium, bone densitometry, and parathyroid antibody (PTH-Ab) were measured in all subjects. Exclusion criteria: Parathyroid dysfunction, multiple endocrine neoplasia, hypercalcemic syndromes, hypervitaminosis D, renal failure, osteoporosis and sarcoidosis. Results: 23/96 patients (24%) had high normal serum calcium (>9.6 mg/dL). The 24-hour urine and total ionized calcium levels were elevated in 2/36 (5.6%) patients in Group B. Baseline serum PTH-intact and PTH Ab were normal in all groups. Group A, 9/45 patients (20%, alfa-2a 44%, 2b, 55%) in and Group-B, 6/36 patients (16.7%) developed elevated PTH levels and none in group C. PTH radionucleotide scan identified 1/36 (2.8%) patient with adenoma in group B. PTH Ab was found 9/45 (20%) in group A, 5/36 (13.9%) in group B, and none in Group C. Conclusion: Interferon alpha has autoimmune effects on parathyroid gland expressing elevated PTH level with PTH Ab without overt clinical manifestation of hyperparathyroidism. A larger sample size is required to confirm the potential effect of IFN alpha on calcium homeostasis, which might explain the symptoms of fatigue in chronic hepatitis C associated with IFN therapy.
Introduction: Chronic hepatitis C (CHC) is no longer a challenging clinical state, with newer DAAs achieving SVR within a shorter duration of therapy. Pegylated Interferon Alfa 2a with ribavirin was the main stay of therapy. Interferon is contraindicated in psychiatric population (schizophrenic, major depression, bipolar, and schizoaffective disorder). This population has a majority of co-morbidities, substance abuse, and advanced fibrosis, along with a poor QOL score. Exclusion criteria: renal failure with CrCl<30, sickle cell, thalassemic syndromes, hemolytic syndrome, co-infections (HBV, HIV), or CHF NYHA Stage IV. Methods: Sixty CHC subjects (n=60, schizophrenia 20/60 [33.3%]), major depression 15/60 (25%), bipolar disorder 20/60 (33.3%), and prior suicidal attempts with depression 5/60 (8.3%), with psychiatric disorder were recruited. Group A: (n=20), simeprevir 150 mg + sofosbuvir 400 mg + ribavirin1,000 mg daily; Group B: (n=20), placebo + sofosbuvir 400 mg + ribavirin 1,000 mg daily; GROUP C: (n=20), simeprevir 150 mg + sofosbuvir 400 mg + vitamin D 5,000 mg daily. Results: Refer to table. Conclusion: Oral combination therapy for interferon ineligible group shows similar SVR rates with better tolerability and safety profile. This special population should be treated with this regiment to prevent cirrhosis and HCC.Table 1: Results
Purpose: HILI is common, with a prevalence of 10% in the US. Transient shift of intra hepatic hemodynamic compromise leads to tissue hypoxia, and induces hypoxia-induced proteins (HIP), heat shock protein 70 and 24 (HSP 24, 70), and endothelial reticular (ER) stress leading to reperfusion injury (RI). Dramatic rise of transaminases is followed by drastic reversal, with restoration of perfusion in weeks. In cirrhotics, HILI might precipitate acute on chronic liver failure (ACLF) requiring liver transplantation. This study evaluated the spontaneous recovery and salvage in HILI utilizing NAC. Methods: Sixty patients (n=60) with mean arterial pressure (MAP) < 35% and normal LFT's at base-line were recruited. Group A (n=28), chronic liver disease (CLD) [ALD, 11/28 (39%); NASH, 9/28 (32%); hepatitis C, 4/28 (14%); hepatitis B, 2/28 (7%); PBC, 1/28 (3%); AIH, 1/28 (3%)]. Group B (n=32), [respiratory failure, 12/32 (37%); CHF, 8/32 (25%); CVA, 2/32 (6%); sepsis, 6/32 (19%); post-op, 4/32 (12%)]. These were then randomized into placebo groups A1 (14) and B1 (16), and IV NAC group for 48 hours - A2 (14) and B2 (16). Serum transaminases, bilirubin, INR, creatinine, and MELD score at 0, 3rd, 6th, 9th, and 12th days, with MAP and modified sequential organ failure assessment (SOFA) score calculated. All patients were allowed standard of care (SOC) and resuscitation if required. Exclusions: Organ transplant, septic shock, hemodialysis, existing malignancy, acute myocardial infarction, Tylenol injury, acute viral hepatitis, organ trauma, and burns. Results: In placebo groups A1, B1: A1 group [Normalized LFTs on third day, (7%), sixth day, (21%), ninth day,(36%), and twelfth day, (21%). 1/14 (7%) died]. B1 CLD group [Normalized LFTs on third day, (19%), sixth day, (44%), ninth day, (25%), while 2/16 (6%) died of sepsis]. NAC Groups: A2 group [Normalized LFTs on third day, (57%), sixth day, (43%), ninth day, (25%), while (7%) (one) died]. Group B2 CLD [Normalized LFTs, third day, (63%), sixth day, (25%), ninth day, 1/16 (6%). One died.] Conclusion: This study postulates that i.v. NAC (used in group A2 and B2) has efficient spontaneous recovery and salvage in non-CLD sub group. B2 (63%) > A2 (57%) in day 3, in CLD NAC (A2) > placebo (A1), clinical recovery over placebo at 3rd day, (44%) over (36%), 6th day. Larger trial is needed to establish the routine usage of i.v. NAC in HILI.
