EUHM Resident Report: What is the relation of bilirubin levels to jaundice abnormalities?

The Bottom Line: Jaundice occurs when there are disruptions along this metabolic pathway, causing  an increase in unconjugated bilirubin (e.g., from increased red blood cell destruction or impaired bilirubin conjugation) or conjugated bilirubin.

Figure 1.  An algorithmic approach to the evaluation of jaundice in adults  page 165

Fargo, M., Grogan, S., & Saguil, A. (n.d.). Evaluation of Jaundice in Adults. American Family Physician., 95(3), 164-168.

Unconjugated hyperbilirubinemia occurs with increased bilirubin production caused by red blood cell destruction, such as hemolytic disorders, and disorders of impaired bilirubin conjugation, such as Gilbert syndrome. Conjugated hyperbilirubinemia occurs in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree.


EUHM Resident Report: Signaling in Stauffer’s Syndrome

The Bottom Line: Against a fundamental contribution for IL-6 in Stauffer’s syndrome is the wide variety of circumstances in which its elevation has no association with inflammatory or cholestatic liver disease. Nevertheless, dysregulated Il-6 acting through disparate signaling cascades is implicated in a variety of autoimmune and inflammatory conditions

Gremida, A., Al-Taee, A., Alcorn, J., & McCarthy, D. (n.d.). Hepatic Dysfunction in Renal Cell Carcinoma: Not What You Think? Digestive Diseases and Sciences., Digestive diseases and sciences. , 2017.

Although the pathophysiology of Stauffer’s syndrome has not been clearly elucidated, tumor overexpression of interleukin 6 (IL-6) is present in 50–80% of patients with RCC and has been suggested as a possible causative factor in one report

EUH Morning Report: In patients with acute alcoholic hepatitis, does steroid therapy increase the risk of GI bleeding compared to no use of steroids?

The Bottom Line: For patients with acute alcoholic hepatitis, there isn’t literature to answer the question of whether steroid therapy increases risk of GI bleeding compared to no use of steroids. For patients with non-acute alcoholic liver disease who do not have concomitant GI bleeding., use of steroids does not appear to increase risk of GI bleeding when compared to placebo or no intervention.


O’Shea RS, Dasarathy S, McCullough AJ, et al. Alcoholic liver disease. Hepatology. 2010 Jan;51(1):307-328. PMID: 20034030. doi: 10.1002/hep.23258

Comment on above article by O’Shea, Dasarathy, and McCullough: Singal AK. Comments on AASLD practice guidelines for alcoholic liver disease. Hepatology. 2010 May;51(5):1860-1861. PMID: 20432268. doi: 10.1002/hep.23605

Rambaldi A, Saconato HH, Christensen E, Thorlund K, Wetterslev J, Gluud C. Systematic review: glucocorticosteroids for alcoholic hepatitis — a Cochrane Hepato-Biliary Group systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Aliment Pharmacol Ther. 2008 Jun;27(12):1167-1178. PMID: 18363896. doi: 10.1111/j.1365-2036.2008.03685.x

References were found in DynaMed Plus. See DynaMed Plus → alcoholic liver disease → treatment → medications → medication to treat acute inflammation for patients with severe alcoholic hepatitis → steroids

Summary of evidence on whether steroid therapy increases the risk of GI bleeding compared to no use of steroids in patients with alcoholic hepatitis (not acute alcoholic hepatitis):

DynaMed Plus states, “efficacy of steroids has not been evaluated in patients with severe alcoholic hepatitis and concomitant…gastrointestinal bleeding,” an “exclusion criteria in many of the early studies of alcoholic hepatitis.”

Only one of the systematic reviews cited in DynaMed Plus on use of steroids versus placebo or no intervention mentioned bleeding as an outcome measure. It states, “Combining the results of four trials providing data demonstrated no significant effects of glucocorticosteroids on…variceal bleeding….Combining the results of the eight trials reporting adverse events demonstrated a significantly higher proportion of patients with adverse events in the glucocorticosteroid group (RR 3.63, 95% CI 1.95–6.76).” The glucocorticosteroids group of 239 patients had “one suspicious of gastrointestinal bleeding.”

VA Resident Report: What is the effectiveness of POEM for achalasia?

Available data suggests POEM is very effective in the relief of symptoms in patients with achalasia. However, POEM is associated with a very high incidence of pathologic reflux. The clinical sequalae of the increase in pathologic reflux are currently incompletely understood, but it is plausible that longer-term outcomes associated with POEM may demonstrate GERD complications such as stricture and/or Barrett esophagus

Shlottmann, F., Luckett, D., Fine, J., Shaheen, N., & Patti, M. (n.d.). Laparoscopic Heller Myotomy Versus Peroral Endoscopic Myotomy (POEM) for Achalasia: A Systematic Review and Meta-analysis. Annals of Surgery., Annals of surgery. , 2017.

Esophageal achalasia is characterized by lack of peristalsis and by a lower esophageal sphincter (LES) which fails to relax appropriately in response to swallowing. Treatment is not curative, but aims to eliminate the outflow resistance caused by the nonrelaxing LES.  In 2010, Inoue et al54 described the results of a new endoscopic technique called per oral endoscopic myotomy (POEM) in 17 patients with esophageal achalasia. They described the endoscopic creation of a submucosal tunnel, which allowed a myotomy by the transection of the circular fibers of the distal esophagus.

VA Resident Report: What are the adverse effects of PPI use on B12 levels?

The Bottom Line: Studies of PPI use and vitamin B12 deficiency have yielded mixed results. Absorption decreased from 3.2 to 0.9% (P ¼ 0.031) in patients on omeprazole 20 mg daily, and from 3.4 to 0.4% in patients on higher doses. Chronic PPI therapy was associated with a 46% decline in median serum B12 levels and subnormal levels in 10% of patients. Others have reported no decreased absorption of vitamin B12 . Older patients are at greatest risk and more likely to have borderline baseline levels.

References: Abraham, N. (2012). Proton pump inhibitors: Potential adverse effects. Current Opinion in Gastroenterology, 28(6), 615-620.   

Summary: High-dose, chronic PPI use is prevalent, despite a high degree of comorbidity in the target population and significant treatment failures . Clinicians must remain cognizant of potential threats and ensure vigilance in their prescribing habits. PPI prescription must be tailored, using an individualized approach that limits use to robust indications

VA Resident Report: What are the gastrointestinal manifestations of cryptosporidium ?

The cardinal symptom is diarrhea, which is typically watery, and accompanied by abdominal cramps, fatigue, nausea, and anorexia. Fever and vomiting may occur. Diarrhea tends to persist longer (median of 5 to 10 days) than that seen with other etiologies and may relapse. In industrialized countries, most cases are immunocompetent adults who experience a self-limited illness. In persons with HIV/AIDS, it is not until the CD4 count falls below ~100 cells/ mm3 that the risk increases for severe, unrelenting disease accompanied by malabsorption, weight loss, and high case fatality, although asymptomatic or mild infection can occur even in this group.

Shirley, D., Moonah, S., & Kotloff, K. (2012). Burden of disease from cryptosporidiosis. Current Opinion in Infectious Diseases, 25(5), 555-563.

Cryptosporidium is an Apicomplexan oocyst-forming protozoan, first recognized as a causative agent of gastroenteritis in 1976. It is one of the most common human enteropathogens worldwide, with young children living in developing countries and persons with HIV/AIDS experiencing more frequent and more severe illness sometimes complicated by malnutrition and long term impairment of physical fitness. Reported cases in industrialized countries are also rising due to the leading role that Cryptosporidium plays as a cause of waterborne outbreaks.

VA Resident Report: At what value does hypertriglyceridemia cause acute pancreatitis?

Acute pancreatitis is a relatively common medical condition with variable aetiologies and a mortality up-to 20%. Gallstones and excess alcohol consumption are the leading aetiologies in the developed world; whilst metabolic, congenital and iatrogenic causes are responsible for 20–25% of cases. Severe hypertriglyceridaemia (HTG) (>10 mmol/L fasting), including chylomicronaemia, is the underlying cause in up to 7% of all cases of acute pancreatitis and is the third most common cause. Acute pancreatitis secondary to hypertriglyceridaemia rarely occurs unless the serum triglyceride concentrations exceed 10 mmol/L

Charlesworth, A., Steger, A., & Crook, M. (2015). Acute pancreatitis associated with severe hypertriglyceridaemia; A retrospective cohort study. International Journal of Surgery., 23(Pt A), 23-27.

The precise mechanism of APHTG is unknown. Hypertriglyceridaemia induced acute pancreatitis rarely occurs unless serum triglyceride concentrations exceed 10 mmol/L. Mild to moderate elevations in triglyceride concentrations (usually, triglycerides less than 5 mmol/L) occurs in up to 47% of patients in the early phase of acute pancreatitis of any aetiology

Intermittent vs Continuous Proton Pump Inhibitor Therapy for High-Risk Bleeding Ulcers A Systematic Review and Meta-analysis

Sachar, Hamita, KetaVaidya, and LorenLaine. “Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis.” JAMA internal medicine 174.11 (2014):1755-62. Conclusion: “Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.”

Checking Hepatitis B surface antigen levels after treatment

HBsAg levels at 6 months of LMV-ADV combination therapy can help predict treatment response. More potent treatments should be considered for cases positive for HBeAg, with high baseline HBV DNA and high HBsAg levels after 6 months treatment.

Kim, Jeong H, et al. “Hepatitis B surface antigen levels at 6 months after treatment can predict the efficacy of lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B.” Clinical and molecular hepatology 20.3 (2014):274-82.

Quantitation of hepatitis B surface antigen is an increasingly popular method to determine the treatment response in chronic hepatitis B patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV- resistant CHB patients treated with adefovir add-on therapy.

Approach to abnormal liver function tests

Note: Figures and table numbers appear above the figures and tables and taken from the following source.

Woreta TA1, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014 Jan;98(1):1-16.

Table 1. Categorization of liver diseases by pattern of elevation of liver enzymes

Liver Disease Category Aminotransferases Alkaline Phosphatase
Hepatocellular ↑↑
Cholestatic ↑↑

Table 5. Patterns of liver enzymes and liver function tests in various hepatobiliary diseases – Part 1

Hepatobiliary Disorder Aminotransferases Alkaline Phosphatase
↑↑↑ (>500 IU/mL) Normal or ↑ to < 3 times normal
Chronic ↑↑ (<300 IU/mL) Normal or ↑ to < 3 times normal
Acute Normal to ↑↑↑ Normal to ↑
Chronic Normal to ↑↑ ↑↑↑ to >4 times normal
Infiltrative Normal to ↑ ↑↑↑ to >4 times normal

Table 5. Patterns of liver enzymes and liver function tests in various hepatobiliary diseases – Part 2

Hepatobiliary Disorder Bilirubin Albumin Prothrombin Time
Normal Usually normal ↑ to >5 seconds above control value portends poor prognosis
Chronic Normal to ↑ Normal or ↓ Often ↑, will not correct with parenteral vitamin K administration
Acute Normal to ↑ Normal Normal
Chronic Normal or ↓ Normal or ↑, will correct with vitamin K administration
Infiltrative Normal Normal Normal

View in article – Fig. 3. Algorithm for evaluation of patients with hepatocellular pattern of liver injury. ANA, antinuclear antibodies; HAV, hepatitis A virus; HBsAG, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus

View in article – Fig. 4. Algorithm for evaluation of patients with elevated alkaline phosphatase. ERCP, endoscopic retrograde cholangiopancreatography

View in article – Figure 5. Algorithm for evaluation of patients with hyperbilirubinemia