Hepatitis C Virus-Infected Apoptotic Hepatocytes Program Macrophages and Hepatic Stellate Cells for Liver Inflammation and Fibrosis Development: Role of Ethanol as a Second Hit.

Hepatocyte apoptosis is a crucially important mechanism for liver disease pathogenesis, and the engulfment of apoptotic bodies (AB) by non-parenchymal cells serves as a leading mechanism of inflammation and fibrosis progression. Previously, we have shown that hepatitis C virus (HCV) and alcohol metabolites induce massive apoptosis in hepatocytes and the spread of HCV-infection to the neighboring uninfected cells. Here, we hypothesize that the capturing of AB by non-parenchymal cells, macrophages and hepatic stellate cells (HSC) changes their phenotype to promote inflammation and fibrosis. In this regard, we generated AB from Huh7.5CYP2E1 (RLW) cells also treated with an acetaldehyde-generating system (AGS) and incubated them with human monocyte-derived macrophages (MDMs) and HSC (LX2 cells). Activation of inflammasomes and pro-fibrotic markers has been tested by RT-PCR and linked to HCV expression and AGS-induced lipid peroxidation in RLW cells. After exposure to AB we observed activation of inflammasomes in MDMs, with a higher effect of AB HCV+, further enhanced by incubation of MDMs with ethanol. In HSC, activation of inflammasomes was modest; however, HCV and AGS exposure induced pro-fibrotic changes. We conclude that HCV as well as lipid peroxidation-adducted proteins packaged in AB may serve as a vehicle for delivery of parenchymal cell cargo to non-parenchymal cells to activate inflammasomes and pro-fibrotic genes and promote liver inflammation and fibrosis.

Heart failure with preserved EF: a bird eye view.

The concept of ''diastolic'' heart failure grew out of the observation that many patients who have the symptoms and signs of heart failure had an apparently normal left ventricular (LV) ejection fraction. Thus it was assumed that since systolic function was ''pre- served'' the problem must lie in diastole, although it is not clear by whom or when this assumption was made. Nevertheless, many guidelines followed on how to diagnose ''diastolic'' heart failure backed up by indicators of diastolic dysfunction derived from Doppler echoardiography. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.

Gastroparesis: a review of current and emerging treatment options.

Gastroparesis is a motility disorder of the stomach causing delay in food emptying from the stomach without any evidence of mechanical obstruction. The majority of cases are idiopathic. Patients need to be diagnosed properly by formal testing, and the evaluation of the severity of the gastroparesis may assist in guiding therapy. Initially, dietary modifications are encouraged, which include frequent and small semisolid-based meals. Promotility medications, like erythromycin, and antiemetics, like prochlorperazine, are offered for symptom relief. In patients who are refractory to pharmacologic treatment, more invasive options, such as intrapyloric botulinum toxin injections, placement of a jejunostomy tube, or implantation of a gastric stimulator, can be considered. Hemin therapy and gastric electric stimulation are emerging treatment options that are still at different stages of research. Regenerative medicine and stem cell-based therapies also hold promise for gastroparesis in the near future.

Pain management in chronic pancreatitis: taming the beast.

Abdominal pain is a principal and in many cases, the only observable symptom of chronic pancreatitis. Like all chronic pain conditions, managing abdominal pain in chronic pancreatitis remains an onerous task for health care providers. Different mechanisms have been postulated in trying to better understand the pathogenesis of pain in chronic pancreatitis. This review seeks to take a broad look at the various options that are available to providers in trying to achieve pain relief and a better quality of life for chronic pancreatitis patients.

Neuromyelitis optica: an often forgotten cause of intractable nausea and vomiting.

Neuromyelitis optica, also known as Devic's disease, is a rare autoimmune disorder in which a patient's immune system affects the optic nerves and the spinal cord, leading to loss of vision and spinal cord dysfunction. We present our experience with a 38-year-old female who presented to our facility with complaints of intractable nausea and vomiting. After extensive evaluation, she was found to have neuromyelitis optica. Her symptoms completely resolved following institution of appropriate therapy. She made a significant recovery and has since been placed on chronic immunosuppressive therapy. Through this article we hope to bring attention to a significant cause of intractable nausea and vomiting that may often be forgotten in general medicine or gastroenterology services.

From Acute Pancreatitis to Stage IV Pancreatic Cancer in 12 Weeks.

Pancreatic cancer is well known to be an aggressive and highly malignant condition with varied ways of presentation. Pancreatic cystic neoplasms are very uncommon causes of pancreatic malignancy and can often be ignored or missed, especially in the early stages. We present the case of a 49-year-old Caucasian male with no past medical history presenting to an outside facility with sudden epigastric pain that was eventually diagnosed as acute pancreatitis. On transfer to our facility, he was eventually found to have metastatic malignant mucinous cystic pancreatic neoplasm. Barely 12 weeks after his initial presentation and following an aggressive hospital course, he passed away.

Eosinophilic gastroenteritis: review of a rare and treatable disease of the gastrointestinal tract.

Eosinophilic gastroenteritis is a rare disease of the gastrointestinal tract characterized by crampy abdominal pain, nausea, vomiting, diarrhea, gastrointestinal bleeding, and weight loss associated with peripheral eosinophilia leading to eosinophilic infiltrates in stomach and intestine, usually in a patient with a prior history of atopy. In this article, we describe our encounter with a 59-year-old female presenting with severe abdominal pain, nausea, vomiting, and weight loss with an extensive evaluation including an upper endoscopy with biopsies resulting in a diagnosis of eosinophilic gastroenteritis. The patient was eventually treated with oral prednisone for three weeks with complete resolution of her symptoms.

Diastolic heart failure: a concise review.

The concept of "diastolic" heart failure grew out of the observation that many patients who have the symptoms and signs of heart failure had an apparently normal left ventricular (LV) ejection fraction. Thus it was assumed that since systolic function was "preserved" the problem must lie in diastole, although it is not clear by whom or when this assumption was made. Nevertheless, many guidelines followed on how to diagnose "diastolic" heart failure backed up by indicators of diastolic dysfunction derived from Doppler echoardiography. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.

Comparing efficacy between regimens in the initial treatment of autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis is a chronic syndrome characterized by auto immunologic features generally including the presence of circulating auto antibodies and high serum globulin concentrations. The American Association for the Study of Liver Diseases (AASLD) recommends initial treatment or induction therapy for autoimmune hepatitis to involve a glucocorticoid alone or a combination of a glucocorticoid and an immunosuppressant. The objective of this study is to review and compare the efficacy of the treatment regimens described above among patients diagnosed with and treated for autoimmune hepatitis over the past 10 years in our center which is a major university based hospital. METHODS: We retrospectively identified patients above the age of 18 years diagnosed with autoimmune hepatitis in our center between February, 2003 and February, 2013 using the ICD-9 code 571.42. The primary outcome of our study was efficacy of the treatment regimen. We defined efficacy by considering 3 scenarios: Complete Resolution, Incomplete Resolution and Treatment Failure. RESULTS: We found differences among 3 treatment groups: patients who received Prednisone and immunosuppressant from the beginning of their treatment course, patients who had an immunosuppressant introduced after about 4 weeks on Prednisone and patients who were placed on Prednisone alone. CONCLUSION: From our study, better efficacy was achieved in the induction phase using a combination of Prednisone and Azathioprine from the beginning of the treatment course.

Pancreatic Cancer and Gastroenterology: A Review.

Pancreatic cancer is a well known aggressive and highly malignant condition with varied ways of presentation. It is the fourth commonest cause of cancer related deaths in the United States. Presenting symptoms and signs are closely related to tumor size and location. Imaging remains the most useful diagnostic modality and is typically applied in an "upgrade fashion" unless in the case of incidentally discovered pancreatic tumors. The role of gastroenterology in the diagnosis and treatment of patients with this condition has expanded recently and is expected to grow even more.

Non-Tuberculous Mycobacterium: A Rare Cause of Granulomatous Hepatitis.

Granulomatous hepatitis is a syndrome usually characterized by fever of unknown origin, myalgias, hepatosplenomegaly, and arthralgias, right upper quadrant abdominal pain or tenderness, with or without an elevation in serum transaminases. In this article, we outline our experience with a 64-year-old male presenting with a 3.5 weeks history of fever of unknown origin, night sweats, extreme fatigue and a 20 lb. weight loss. He had an extensive evaluation including 2 liver biopsies that was indicative of fibrin ring granulomas and a positive PCR for Mycobacterium chelonae-abscessus. He was eventually treated empirically with antibiotics that led to an improvement of his symptoms.

Hepatic Angiosarcoma: An Unusual Case of Intractable Gastrointestinal Bleeding.

Hepatic Angiosarcoma is an extremely rare malignant neoplasm of the vascular or lymphatic endothelium accounting for about 2% of all sarcomas. It is considered idiopathic in up to 70% of cases. We describe the case of a 32-year female transferred to our center for evaluation of intractable gastrointestinal bleeding. Definitive diagnosis remained elusive despite multiple endoscopic assessments with repeated cauterization of arteriovenous malformations (AVMs). Autopsy results confirmed metastatic hepatic Angiosarcoma.