8/15 (HUP): alcoholic hepatitis

Late post thanks to boards! A big thanks to Dr. Vandana Khungar for helping us through the case of a young man who presented with jaundice and abdominal pain with a bilirubin of 51 and was ultimately diagnosed with acute alcoholic hepatitis (for which he got a liver transplant).

Key features of alcoholic hepatitis

  1. Even though we often think of alcoholic hepatitis as ‘acute’, its actually more often a manifestation of chronic heavy alcohol intake (>80g/day for a decade or more).

Ever wonder how much alcohol is in a ‘standard’ drink? Take a look!

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Remember that alcoholic hepatitis (AH) can be superimposed on underlying cirrhosis/chronic liver disease.

  • Patients can present with fever, tender hepatomegaly and leukocytosis; it can sometimes be difficult to distinguish from other causes of acute hepatitis, as well as sepsis/infection
  • Some series have shown that >50% of patients have abdominal bruits; other stigmata of liver disease (ascites, encephalopathy) may be present either with or without underlying liver disease
  • The AST:ALT ratio will usually be >2:1: thought to be due to hepatic deficiency of pyridoxal 5′-phosphate in alcoholics (a cofactor for the enzymatic activity of ALT); so the ratio is really a failure of ALT to increase appropriately

Risk stratification for alcoholic hepatitis

There are several risk scores used for EtOH hepatitis:

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Lucey. NEJM 2009.


Maddrey’s discriminant function: estimates EtOH severity; a score >32 is considered severe.
Glasgow score: used to estimate likelihood of benefit from steroids. Rarely used in clinical practice
Lille score: helps decide whether to stop or continue steroids after 1 week (ie which patients won’t benefit from steroids no matter what given the severity of their hepatitis)

How is alcoholic hepatitis managed?

  • Supportive care (fluids, antibiotics if needed, abstinence, nutritional support)
  • The big debate is over the role of prednisolone and pentoxifylline (a TNF-a inhibitor) in the treatment of alcoholic hepatitis. You can read the details of the STOPAH trial below (which compared the two), but the short answer is that it’s not totally clear that one is better than the other.
  • One major flaw of STOPAH may have been that in the groups randomized to steroids, the investigators continued prednisolone for 28 days instead of using the Lille score to stop steroids for those people that wouldn’t have benefited; in doing so, they may have driven up mortality due to infection in the steroid group and diminished any apparent benefit of prednisolone!
  • In clinical practice (at least at Penn), prednisolone is often started after 48 hours of negative infectious workup, as long as they don’t have renal failure (a population that was excluded in STOPAH, due at least in part to concerns about bleeding risk)

See reference #2 below for more information about the role of liver transplant in treating alcoholic hepatitis!


  1. Thursz M et al. Prednisolone or Pentoxifylline for Alcoholic Hepatitis (STOPAH). NEJM 2015.
  2. Saberi, B. et al. 2016. Current Management of Alcoholic Hepatitis and Future TherapiesJournal of Clinical and Translational Hepatology. 4, 2 (2016), 113–122.
  3. Lucey et al. 2009. Alcoholic Hepatitis. NEJM.

8/17 (HUP): diffuse GGOs and PCP

Thanks to Tom Franzon and Ben Manning for presenting two (different) patients who presented with subacute shortness of breath and were found to have diffuse groundglass opacities (GGOs) on chest CT and were ultimately diagnosed with HIV for the first time.

Along the way, we went through a diagnostic approach for diffuse ground glass opacities. Developing a differential for just ‘GGOs’ is a Herculean task, but creating a differential for diffuse GGOs (as opposed to scattered GGOs, particularly in association with some other consolidation) is actually much easier to do.

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Diffuse GGOs in a patient with methotrexate pneumonitis. AJR 2005.

Here’s a table from a paper by Penn radiologist/wizard Wally Miller:

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Miller and Shah, AJR 2005

This man was ultimately diagnosed with PCP pneumonia.

A few key points about diagnostic testing related to HIV and opportunistic infections:

  • Beta-D-glucan has excellent sensitivity (~95%) and specificity (~70-80%) for the diagnosis of PCP; in a patient who truly has PCP, BDG levels will likely be >400-500
  • CD4 counts can decrease with periods of acute/critical illness, so the CD4% may be a more stable marker to follow in someone with HIV, as it shouldn’t change all that much
    • An absolute CD4 count >500 corresponds to a CD4% of >30%

    • An absolute CD4 count between 200-500 corresponds to a CD4% of 15 to 30%

    • An absolute CD4 count <200 cells/microL corresponds to a CD4% of <15%

  • Most of the time, non-HIV related low CD4 counts don’t predispose to opportunistic infections, with the exception of idiopathic CD4+ lymphopenia— patients with this condition behave similarly to HIV+ patients with low CD4 counts in terms of OI susceptibility, except that they don’t have HIV!
  • Legionella urine antigen tests only for Legionella pneumophila serovar 1, so as a whole it has about a 70% sensitivity
  • The histoplasma urine antigen is best in HIV+ patients with disseminated disease (95% sens); sensitivity is probably similar in non-HIV patients
    • It’s really not a great test for less severe pulmonary histo or chronic cavitary histo, especially in non-AIDS patients
    • It can be false positive with other endemic fungi (Blasto, coccidio, etc)
  • A brief note on IRIS
    • It represents ‘unmasking’ of an underlying, unrecognized infection as the immune system ‘reconstitutes’ itself while on ART
    • Many pathogens (TB, NTBMB, PCP, HBV, crypto) have been associated with IRIS, while others (ex: toxo) are rarely associated with it
    • Generally develops when pre-ART CD4 nadir <100, and generally develop within one week to a few months after initiation of ART (depending on the kind of infection, host characteristics, etc)


  1. Miller, Wally Jr and Shah, Rosita. Isolated Diffuse Ground-Glass Opacity in Thoracic CT: Causes and Clinical Presentations. AJR 2005.
  2. Kauffman, C. Histoplasmosis: a clinical and laboratory update. 2007.
  3. Murdoch et al. Immune Reconstitution Inflammatory Syndrome (IRIS): review of common infectious manifestations and treatment options. 2007.

8/9 (HUP): pulmonary hypertension and PVOD/PCH

Thank you, Jesse Platt, for walking us through the complicated case of a 66 year old man with months of worsening dyspnea and hypoxia of unclear origin who was diagnosed with (very) severe pulmonary hypertension, and is thought to have either PVOD or pulmonary capillary hemangiomatosis (PCH)!

We went through the classification of pulmonary hypertension:

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Simonneau et al. JACC 2013.

Suggested approach to etiologic workup of PH

  1. Physical exam (look for clubbing, parasternal heave, S2, crackles on lung exam, signs of cirrhosis, etc)
  2. Chest X-ray (look for venous congestion, prominent PA, ILD)
  3. CT chest (looking for ILD, parenchymal lung disease, nodules, mosaic attenuation (what is that?) which may suggest areas of heterogenous blood flow or air trapping)
  4. Transthoracic echo (with bubble/contrast): looking for intracardiac (early bubbles) or intrapulmonary (late bubbles), estimate of RV and PA pressures, signs of RV dilation or volume/pressure overload
  5. Ventilation/perfusion (V/Q) scan: this is the gold standard for ruling out CTEPH. Remember that CTEPH doesn’t require a history of repeated PEs; it really represents a dysregulated healing response to vasoactive cytokines from even a single PE in the past!
  6. Consider PFTs and nocturnal polysomnography (to rule out OSA)
  7. Consider ABG (to confirm hypoxia, and also if concern for shunt physiology)
  8. Consider blood testing for other causes of PH (HIV, ANA [only send dsDNA, RNP if ANA+ ), RF, ANCA)
  9. Right heart catheterization: gold standard for diagnosing/confirming PH (defined as a mean PA pressure >25mm Hg)

Ultimately, this patient’s testing (RHC w/ severe pHTN, TTE w/ LVEF 60% but moderate RV dilation and late bubbles suggestive of pulmonary AVMs, CT chest w/ scattered basilar nodules with diffuse mosaic attenuation) suggested a diagnosis of PVOD vs PCH as the diagnosis.

In brief, PVOD is characterized by smooth muscle hypertrophy within pulmonary veins and venules, whereas PCH is marked by atypical capillary proliferation; both cause pulmonary hypertension, and can be difficult to differentiate from PH of other causes.

We learned that severe hypoxia (10L O2 in this case) is uncommon with most causes of PH, and should make you think of:

  2. CTEPH
  3. Large intracardiac/intrapulmonary shunt

See this table to see a comparison of PH, PVOD and PH:

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Chaisson 2016

Two final pearls

  1. PVOD and PCH patients are at a higher risk of pulmonary edema with vasodilator therapy given their capillary hemodynamics
  2. PASPs from echos are derived from the maximum tricuspid valve velocity; but this is reliant on good views on echo, and varies based on underlying comorbidities, etc. Generally TTE PASPs are thought to be off from RHC PASPs by about 10mm Hg (want more info?)
  3. There are case reports of PCH being treated with doxycycline, which apparently has anti-angiogenic properties! (see #1 below)


  1. Ginns et al. Pulmonary Capillary Hemangiomatosis With Atypical Endotheliomatosis: Successful Antiangiogenic Therapy With Doxycycline. Chest 2003.
  2. Chaisson et al. Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-occlusive Disease. Clinics in Chest Medicine 2016.
  3. Simonneau et al. Updated clinical classification of pulmonary hypertension. JACC 2013.

8/8 (HUP): CCB toxicity

Thanks to Dr. Francis DeRoos for walking us through a case of a young woman who presented with shock, and was ultimately found to have overdosed on calcium-channel blockers.

First, we talked about the importance of (1) the physical exam and (2) the EKG in diagnosing and risk stratifying patients with toxic ingestions. Assessing the skin, pupils, and sweat/lack thereof can give you valuable clues. See the toxidromes post from a few months ago for more info.

Here’s a cute chart that illustrates that:

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Common toxidromes (source: http://www.sketchymedicine.com)

We also talked about various causes of drug-induced bradycardia:

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Lithium tends to cause bradycardia most commonly in patients with underlying cardiac disease. Amiodarone has particularly been known to cause bradycardia in concert with certain of the new HCV medications (sofosbuvir or daclatasvir), including slow VT!

CCB toxicity can cause a variety of ECG changes, including sinus bradycardia and varying degrees of AV blockade. Remember to look at the rhythm strip carefully to make sure you’re not missing complete heart block!

Treatment options for CCB toxicity

  1. Calcium: may improve inotropy and blood pressure. You can give either calcium gluconate (short acting, can give peripherally but lower Ca content) or calcium chloride (3x the Ca content of Ca gluconate, must give centrally given risk of tissue damage w/ extravasation).
  2. Pacing: unlikely to be of much benefit even in hemodynamically significant bradycardia, given that the CCB is still bathing cardiomyoctes with its negative chronotropic effect.
  3. Vasopressors: something (like norepinephrine) with inotropic and vasoconstrictive effects is best, but there’s no trial proving the superiority of one vs another. Large doses may be needed.
  4. High-dose insulin/euglycemic therapy: CCBs block the calcium-dependent release of insulin from pancreatic beta cells, while at the same time increasing glycogenolysis. Insulin is also postulated to have a positive inotropic effect, especially in these patients in whom CCBs are exerting a negative inotropic effect. Massive doses of insulin (to the tune of 0.5-1U/kg/hour) may be needed given (along with dextrose) to maintain euglycemia.
  5. Lipid formulations: intravenous lipid rescue (initially used for bupivicaine toxicity) can be used as a ‘lipid sink’ to bind up unbound CCB. This is not without risks, as it can cause lipemic serum and higher rates of pancreatitis!
  6. ECMO/CPB: with refractory shock, there is also a role for putting patients on ECMO while using adjunctive therapies (above) to support them

Lastly, the paper of the day– which suggests that earlier Lasix administration in patients with decompensated heart failure may have a mortality benefit! See their central illustration, which suggests that there is a critical period (<60 min) where early diuretic administration might be particularly beneficial:

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  1. Matsue, Y. et al. 2017. Time-to-Furosemide Treatment and Mortality in Patients Hospitalized With Acute Heart Failure. Journal of the American College of Cardiology. 69, 25 (2017), 3042–3051.
  2. Kerns, W. 2007. Management of β-Adrenergic Blocker and Calcium Channel Antagonist Toxicity. Emergency Medicine Clinics of North America. 25, 2 (2007), 309–331.
  3. Life in the fast lane. Calcium Channel Blocker Toxicity.