Edward Sheen

Adverse effects of long-term proton pump inhibitor therapy.

Proton pump inhibitors have an excellent safety profile and have become one of the most commonly prescribed class of drugs in primary and specialty care. Long-term, sometimes lifetime, use is becoming increasingly common, often without appropriate indications. This paper is a detailed review of the current evidence on this important topic, focusing on the potential adverse effects of long-term proton pump inhibitor use that have generated the greatest concern: B12 deficiency; iron deficiency; hypomagnesemia; increased susceptibility to pneumonia, enteric infections, and fractures; hypergastrinemia and cancer; drug interactions; and birth defects. We explain the pathophysiological mechanisms that may underlie each of these relationships, review the existing evidence, and discuss implications for clinical management. The benefits of proton pump inhibitor use outweigh its risks in most patients. Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from long-term therapy.

Nonresponse to Interferon-α Based Treatment for Chronic Hepatitis C Infection Is Associated with Increased Hazard of Cirrhosis

Background The long-term consequences of unsuccessful interferon-α based hepatitis C treatment on liver disease progression and survival have not been fully explored. Methods and Findings We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-α based treatment between 1992 and 2007. They were assessed for the probability of developing cirrhosis and of dying during follow-up using Cox proportional hazards models, stratified by pretreatment liver fibrosis stage and adjusted for known risk factors for cirrhosis and characteristics affecting treatment selection. The major predictor was a time-dependent covariate for treatment outcome among four patient groups: 1) patients with sustained virological response to treatment; 2) treatment relapsers; 3) treatment nonresponders; and 4) never treated patients. Treatment nonresponders in both cohorts had a statistically significantly increased hazard of cirrhosis compared to never treated patients, as stratified by pretreatment liver fibrosis stage and adjusted for clinical and psychosocial risk factors that disproportionately affect patients who were ineligible for treatment (Veterans Affairs HR = 2.35, CI 1.18–4.69, mean follow-up 10 years, and University Hospital HR = 5.90, CI 1.50–23.24, mean follow-up 7.7 years). Despite their increased risk for liver disease progression, the overall survival of nonresponders in both cohorts was not significantly different from that of never treated patients. Conclusion These unexpected findings suggest that patients who receive interferon-α based therapies but fail to clear the hepatitis C virus may have an increased hazard of cirrhosis compared to untreated patients.

Health Care Reform and the Road Ahead for Gastroenterology

The Supreme Court has weighed in on the constitutionality of the Patient Protection and Affordable Care Act (ACA). Few people predicted that the individual mandate to purchase insurance would be upheld because of Congressional authority to levy a tax. Fewer still predicted the ruling on Medicaid expansion. In this month’s “Practice Management: The Road Ahead” segment, 4 of us have tried to outline (within editorial word limits) the potential implications of the Supreme Court ruling. Although we await election results, make no mistake—the ACA will move forward, and it will have profound implications for gastroenterology. Our training programs and safety net hospitals will suffer (see Taylor IL and Clinchy RM. Clinical Gastroenterology and Hepatology 2012;10:828–830), colorectal cancer screening paradigms may change as accountable care organizations develop, and each practice will be challenged to understand their State’s reaction to Medicaid expansion. The American Gastroenterological Association will continue to monitor the national landscape, educate you about The Road Ahead, and advocate for our members and patients.

The efficacy of entecavir therapy in chronic hepatitis B patients with suboptimal response to adevofir

Aliment Pharmacol Ther 2011; 34: 767–774

Supreme Court Review of the Affordable Care Act: The Future of Health Care Reform and Practice of Gastroenterology

After decades of failed attempts to enact comprehensive health care reform, President Obama signed the Patient Protection and Affordable Care Act into law on March 23, 2010. The Affordable Care Act (ACA) has been regarded as the most significant piece of domestic policy legislation since the establishment of Medicare in 1965. The ACA would cover an estimated 32 of the 50 million uninsured Americans by expanding Medicaid, providing subsidies to lower income individuals, establishing health insurance exchanges, and restricting insurance companies from excluding patients from coverage. The ACA also includes many payment and health care delivery system reforms intended to improve quality of care and control health care spending. Soon after passage of the ACA, numerous states and interest groups filed suits challenging its legality. Supreme Court consideration was requested in five cases and the Supreme Court selected one case, brought by 26 states, for review. Oral arguments were heard this spring, March 26–28. The decision will have far reaching consequences for health care in America and the practice of gastroenterology for decades to come. This article reviews the four major issues before the Supreme Court and implications for health care reform and future practice of gastroenterology. Payment reforms, increased accountability, significant pressures for cost control, and new care delivery models will significantly change the future practice of gastroenterology. With these challenges however is a historic opportunity to improve access to care and help realize a more equitable, sustainable, and innovative health care system.

Isoniazid hepatotoxicity requiring liver transplantation.

A 65-year-old female Peruvian immigrant was initially evaluated for potential initiation of anti-tumor necrosis factor (TNF)-a therapy for her poorly controlled rheumatoid arthritis. The patient had a history of thyroid cancer that had required thyroidectomy and replacement levothyroxine. The patient’s quantiferon test was positive, and she also had a history of aspartate transaminase (AST) and alanine transaminase (ALT) values between 40 and 60 IU/ L for at least the previous 4 years. Previous laboratory evaluation had revealed a positive anti-nuclear antibody (ANA) titer at dilution of 1:640 with homogeneous pattern, positive anti-smooth muscle antibody, and elevated immunoglobulin G (IgG) levels at 2,310 mg/dL. The patient, however, denied any prior history of chronic liver disease; consequently, no further evaluation was pursued. Isoniazid (INH) prophylaxis for latent tuberculosis infection (LTBI), was instituted for an expected nine-month course. The patient did not take any dietary or herbal supplements and did not drink alcohol. One month after initiating INH, the patient sought evaluation for jaundice, nausea, and fatigue. Her total bilirubin level was 11.3 mg/ dL, direct bilirubin level 8.6 mg/dL, AST 1,642 IU/L, ALT 1,576 IU/L, alkaline phosphatase 246 IU/L, albumin 3.0 g/ dL, and international normalized ratio 1.2. Serologic testing for acute viral hepatitis was negative. Because of presumed INH hepatotoxicity, INH was discontinued. Two weeks later, the patient complained of worsening nausea as well as new-onset ascites and lower extremity edema. Her total bilirubin was 27.8 mg/dL, direct bilirubin 21.6 mg/ dL, AST 726 IU/L, ALT 588 IU/L, alkaline phosphatase 254 IU/L, albumin 2.4 g/dL, and international normalized ratio 1.8. Triphasic contrast CT imaging demonstrated a shrunken and nodular liver and moderate-volume ascites. The patient was treated with spironolactone, furosemide, and subcutaneous vitamin K, but continued to feel poorly. Two weeks later, she developed encephalopathy with worsening renal insufficiency and international normalized ratio rising to 2.3. She was transferred to Stanford Hospital for urgent liver transplant evaluation. Upon transfer, WBC was 14.2 K/lL, platelet count 112 K/lL, sodium level 126 mmol/L, potassium level 5.4 mmol/L, CO2 18 mmol/L, BUN 57 mg/dL, creatinine 2.9 mg/dL, AST 229 IU/L, ALT 251 IU/L, total bilirubin 26.1 mg/dL, alkaline phosphatase 502 IU/L, albumin 1.4 g/dL, and international normalized ratio 2.6. The patient’s model for end-stage liver disease (MELD) score was 40. Expedited transplant evaluation was initiated, and supportive care was provided with lactulose, rifaximin, and intravenous albumin. The patient also received intravenous vitamin K as well as fresh frozen plasma transfusions. Despite these measures, the patient experienced worsening encephalopathy, azotemia, and hepatic synthetic dysfunction. On E. Sheen (&) M. H. Nguyen Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, Stanford University, Alway Building, Room M-211, 300 Pasteur Drive, Stanford, CA 94305, USA e-mail: esheen@stanford.edu

Two Evils: Gastrocolic Fistula and Heart Failure

A 35-year old man was transferred to Stanford Hospital for further care of Crohn’s disease (CD) pancolitis complicated by fistula formation. He had no significant past medical history other than his CD, which was diagnosed three and a half years before admission. He had no prior history of heart disease and he had not experienced any recent symptoms of viral infection. He had, nevertheless, noted gradual worsening of his functional status over the year before admission, with increasing fatigue, dyspnea on exertion, and intermittent lower extremity edema. There was no family history of inflammatory bowel disease or heart failure. The patient did not smoke, drink, or use any illicit drugs, and was currently unemployed. The patient had been diagnosed with CD with terminal ileitis and perianal involvement and treated with adalimumab and methotrexate, with previous lack of response to infliximab. He had lost health insurance coverage several times after his diagnosis of CD and had thus been unable to receive anti-tumor necrosis factor (TNF)-a therapy at times. He was admitted to an outside hospital with 50 lb weight loss accompanied by post-prandial feculent emesis. Computed tomography (CT) of the abdomen revealed severe colitis and gastrocolic fistula extending from the posterior gastric wall to the distal transverse colon (Fig. 1). A left ventricular thrombus was also detected by CT imaging. Transthoracic echocardiography revealed severe left ventricular dysfunction with ejection fraction 20–25 %. The patient was subsequently empirically treated with ceftriaxone, IV heparin, peripheral parenteral nutrition (PPN), and ‘‘bowel rest’’, and transferred to Stanford Hospital to receive a higher level of care. At Stanford, the patient was afebrile, normotensive, and remained clinically stable without low output heart failure. The possibilities of viral myocarditis, familial cardiomyopathy, and substance abuse-induced cardiomyopathy were considered but there was no evidence of these etiologies. The patient was tachycardic on presentation but this was thought to be most likely a compensatory response to his heart failure. The possibility of tachycardia-induced cardiomyopathy was considered but was not supported by his disease course. Cardiac magnetic resonance imaging (MRI) revealed marked left ventricular enlargement with substantially reduced systolic function, severe diffuse ventricular hypokinesis, and estimated left ventricular ejection fraction (LVEF) of 14 % (Fig. 2). Left ventricular trabeculations were present but did not meet criteria for noncompaction cardiomyopathy. The patient was initially treated with low-dose carvedilol, digoxin, and spironolactone. Lisinopril was also initiated but was subsequently discontinued because of hypotension. Repeat echocardiogram confirmed the presence of a left ventricular thrombus necessitating anticoagulation with E. Sheen (&) Division of Gastroenterology and Hepatology, Department of Medicine, Stanford School of Medicine, Alway Building, Room M-211, 300 Pasteur Drive, Stanford, CA 94305, USA e-mail: esheen@stanford.edu

Higher mortality and hospital charges in patients with cirrhosis and acute respiratory illness: a population-based study

Both cirrhosis and acute respiratory illness (ARI) carry substantial disease and financial burden. To compare hospitalized patients with cirrhosis with ARI to cirrhotic patients without ARI, a retrospective cohort study was conducted using the California Office of Statewide Health Planning and Development database. To balance the groups, propensity score matching (PSM) was used. We identified a total of 46,192 cirrhotic patients during the three study periods (14,049, 15,699, and 16,444 patients, respectively). Among patients hospitalized with cirrhosis, the ARI prevalence was higher in older age groups (p < 0.001), the Asian population (p = 0.002), non-Hispanic population (p = 0.001), and among Medicare patients (p < 0.001). Compared to controls, patients with ARI had 53.8% higher adjusted hospital charge (

Economic and clinical burden of viral hepatitis in California: A population-based study with longitudinal analysis

122,555 vs.

Toward a 21st-Century Health Care System: Recommendations for Health Care Reform

79,685 per patient per admission, p < 0.001) and 35.0% higher adjusted in-hospital mortality (p < 0.001). Older patients, patients with alcoholic liver disease or liver cancer were at particularly higher risk (adjusted hazard ratio = 2.94 (95% CI: 2.26–3.83), 1.22 (95% CI: 1.02–1.45), and 2.17 (95% CI: 1.76–2.68) respectively, p = 0.028 to <0.001). Mortality rates and hospital charges in hospitalized cirrhotic patients with ARI were higher than in cirrhotic controls without ARI. Preventive efforts such as influenza and pneumococcal vaccination, especially in older patients and those with liver cancer, or alcoholic liver disease, would be of value.