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Open Access Publications from the University of California

Scholarly Works (27 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2019)

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) affect 75-100 million U.S. citizens and carries an increased risk for liver, cardiovascular and cancer related morbidity and mortality. Similarly, chronic hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma (HCC) worldwide. Understanding the clinical, epidemiology and biological causes of NAFLD, with or without HCV, is of utmost importance given the lack of targeted therapies and the large economic burden it places on healthcare. Accordingly, we aimed to identify the clinical and epidemiological factors that affect HCV treatment in the setting of NAFLD and understand the risk of HCC in the NAFLD patients, compared to viral etiologies of HCC. To do so, we utilized the Electronic Medical Records of the Veterans Affairs Health Care System (VA HCS), the largest single-payer health system in the U.S., and UCLA Medical Center, one of the largest tertiary-care liver transplantation centers in the country. To further understand the molecular basis of NAFLD and NASH, we studied liver RNA-sequencing from a cohort of bariatric surgery patients with detailed liver histopathological data. We found that NAFLD does not affect HCV cure and that resolution of HCV leads to improvements in insulin resistance. We also observe that NAFLD HCC can occur in a non-cirrhosis background in 18% of cases and that older Hispanic patients with larger BMIs were more likely to have cirrhosis when diagnosed with NAFLD HCC. Through analysis of our transcriptomics human liver RNA-sequencing, we identify a lipid responsive non-coding gene, OLMALINC, as a novel enhancer RNA (eRNA) in the cis regulation of stearoyl Co-A desature, a key triglyceride gene that has been a therapeutic target in NASH human clinical trials. In this work, we present the clinical and epidemiological phenotypes of NAFLD and identify important associations between insulin resistance, dyslipidemia, and BMI in HCC. Our functional genomics data in statin-users help us identify the first eRNA in lipid metabolism described to date. Bridging the understanding of clinical phenotypes that translate to human-relevant molecular studies is key to elucidating the mechanisms of NAFLD, NASH and HCC.

  • 1 supplemental file
Cover page: From Bedside to Bench-side: the Clinical, Epidemiological and Molecular Basis for Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma
  • Article
  • Peer Reviewed
UCLA Previously Published Works (2015)

Opinion statement

Hypersecretory conditions affecting the stomach account for significant morbidity and mortality manifested in some cases with peptic ulcer, gastrointestinal hemorrhage, and/or gastroesophageal reflux disease (GERD). The diagnosis of gastric acid hypersecretory states can be challenging and relies on the use of quantitative assays to measure gastric acid secretion and serum gastrin. The most common etiology for hypergastrinemia is the use of potent gastric acid inhibitors such as the proton pump inhibitors. The differential diagnosis of this condition is of critical importance, and will dictate management decisions. Conditions such as atrophic gastritis are relatively benign and can lead to hypergastrinemia without the presence of gastric acid hypersecretion. Zollinger-Ellison syndrome, on the other hand, causes hypergastrinemia with profound gastric acid hypersecretion [1]. More common causes of hypergastrinemia include gastric outlet obstruction, ileus, and chronic renal failure [2]. In most cases, proton pump inhibitors will be used to manage these conditions. In some instances, surgical therapy may be required. This chapter will review the important clinical causes of gastric acid hypersecretion and provide insights to the best medical management options to better care for patients with these disorders.
    Cover page: Gastric Hypersecretory States: Investigation and Management
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2020)
    The primary purpose of variceal screening in patients with cirrhosis is to detect gastroesophageal varices at high risk of hemorrhage and implement preventative intervention(s). It was previously recommended that all patients with cirrhosis undergo initial and periodic longitudinal variceal screening via upper endoscopy. However, there has been growing interest and methods to identify patients with cirrhosis who may not have clinically significant portal hypertension and therefore be unlikely to have varices requiring intervention or benefit from upper endoscopy. Because the population of patients with compensated advanced chronic liver disease continues to grow, it is neither beneficial nor cost-effective to perform endoscopic variceal screening in all patients. Therefore, there is ongoing research into the development of methods to non-invasively risk stratify patients with cirrhosis for the presence of high-risk esophageal varices and effectively limit the population that undergoes endoscopic variceal screening. This is particularly important and timely in light of increasing healthcare reform and barriers to healthcare. In this review, we discuss and compare, with respect to test characteristics and clinical applicability, the available methods used to non-invasively predict the presence of esophageal varices.
      Cover page: Noninvasive scores for the prediction of esophageal varices and risk stratification in patients with cirrhosis
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2020)
      Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Epidemiological studies have not only shed light on the prevalence and incidence of the disease but have also unmasked important environmental risk factors, including the role of diabetes and dyslipidemia in disease pathogenesis. Genetic association studies have identified single nucleotide polymorphisms implicated in NAFLD-HCC, many of which are part of lipid metabolism pathways. Through these clinical studies and subsequently, translational and basic research, the role of statins as a chemoprotective agent has also emerged with ongoing clinical trials assessing their utility in HCC prevention and treatment. In this review, we summarize the recent epidemiological studies describing the burden of NAFLD-HCC in different patient populations and countries. We discuss the genetic and environmental risk factors for NAFLD-HCC and highlight the chemoprotective role of statins and aspirin. We also summarize what is known about NAFLD-HCC in the cirrhosis and non-cirrhosis populations and briefly address the role of surveillance in NAFLD-HCC patients.
        Cover page: Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)
        At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System) that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet) and corpus-predominant (autoimmune). Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word "metaplastic" in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG) and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world.
          Cover page: Autoimmune atrophic gastritis: current perspectives
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2017)

          Introduction

          The role of EUS-guided FNA as a highly sensitive modality in the diagnosis of pancreatic adenocarcinoma is well documented. However, there is little published data on the role of EUS-FNA in diagnosing pancreatic neuroendocrine tumors (NETs).

          Objective

          The aim of this study is to compare the sensitivity of EUS-FNA to that of CT-FNA for diagnosing pancreatic NETs.

          Methods

          This is a single institution retrospective analysis of the operating characteristics of EUS-FNA and CT-FNA in detecting pancreatic NETs. Only patients with a final diagnosis of pancreatic NET were selected for this study. Procedure related data, including tumor size and location, and presence of a cytotechnologist were recorded. The results of each FNA were compared to the final clinico-pathological diagnosis to calculate sensitivity.

          Results

          Twenty-eight patients undergoing FNA (19 by EUS, 9 by CT) were analyzed. NETs diagnosed by EUS-FNA were smaller compared with CT-FNA (2.7 ± 0.9cm vs. 6.5 ± 2.1cm, p = 0.009) and were more often found in the pancreatic head (47.4% vs. 11.1%, p = 0.035). There were no significant differences in sensitivity between EUS-FNA and CT-FNA specimens (73.7% vs. 88.9%, p = 0.33).

          Conclusion

          EUS-guided FNA is as sensitive as CT-guided FNA in diagnosing pancreatic NETs, but its main advantage is in the diagnosis of smaller pancreatic NETs in the head of the pancreas. It may also be the preferred approach in the diagnosis of multifocal pancreatic NETs in the setting of MEN I Syndrome.
            Cover page: Endoscopic Ultrasound-Guided Fine Needle Aspiration Accurately Diagnoses Smaller Pancreatic Neuroendocrine Tumors Compared To Computer Tomography-Guided Fine Needle Aspiration.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2020)
            Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15-0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17-0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59-58.82) and high BMI (OR = 1.19, 95% CI 1.07-1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p < 0.0001). After treatments, NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Non-Hispanic ethnicity and normal BMI differentiated non-cirrhosis versus cirrhosis NAFLD HCC. Further studies are warranted to identify additional biomarkers to stratify NAFLD patients without cirrhosis who are at risk for HCC.
              Cover page: Improved survival after treatments of patients with nonalcoholic fatty liver disease associated hepatocellular carcinoma
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2017)
              Hereditary hemorrhagic telangiectasia (HHT), also called Osler-Weber-Rendu syndrome, is an autosomal dominant genetic disease that affects the vasculature of numerous organs. The prevalence of HHT is estimated to be between 1.5 and 2 persons per 10,000. While there is still much to learn about this condition, there is an increasing understanding its underlying pathophysiology, genetic basis, presentations, and management. Recognizing that the clinical manifestations of HHT can involve a number of organ systems will provide clinicians with a higher index of suspicion for the disease. This early diagnosis and genotyping can greatly reduce mortality for a patient with HHT through appropriate screening for complications. This review will focus on the gastrointestinal manifestations of HHT and how these can dictate treatment and prognosis.
                Cover page: Gastrointestinal Manifestations of Hereditary Hemorrhagic Telangiectasia (HHT): A Systematic Review of the LiteratureCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2017)
                AIM:To determine how sustained virological response at 12 wk (SVR12) with direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection affects chronic kidney disease (CKD) progression. METHODS:A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates. RESULTS:Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate (eGFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 mL/min ± 0.75 mL/min per 1.73 m2 compared to a decline in eGFR of 11.0 mL/min ± 2.81 mL/min per 1.73 m2 in patients who did not achieve SVR12 (P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in eGFR in those with untreated HCV over 2 years was 2.8 mL/min ± 1.0 mL/min per 1.73 m2, which was not significantly different from the eGFR decline noted in HCV-treated patients who achieved SVR12 (P = 0.43). CONCLUSION:Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.
                  Cover page: Impact of sustained virologic response on chronic kidney disease progression in hepatitis C
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2017)
                  The voltage gated sodium channel SCN4A mutations account for non-dystrophic myotonia and include a heterogeneous group of conditions that include hyperkalemic periodic paralysis, paramyotonica congenita, potassium-aggravated myotonia, and hypokalemic periodic paralysis type 2. This case report proposes that a rare variant p.Pro1629Leu in SCN4A can cause a skeletal muscle deficit with intermittent dysphagia.
                    Cover page: A Sodium Channel Myotonia Presenting with Intermittent Dysphagia as a Manifestation of a Rare SCN4A Variant
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