Category Archives: Gastroenterology and Hepatology

SFGH Morning Report 10.6.17 – Cirrhosis – HCV Treatment and altered mental status

Thanks Dan for presenting an interesting case of a middle age man with HCV cirrhosis c/b HCC in the ICU after a motor vehicle accident with altered mental status, hyperkalemia, and volume overload.  Dr. Cello gave us some awesome pearls!

Learning Pearls

  • Of all the causes of cirrhosis there is one that will not progress to HCC: Congestive hepatopathy from heart failure
  • There is no role for beta-blocker treatment to prevent recurrent variceal bleeds after banding has been performed because the varices have a very low incidence of bleeding.  These patients may have upper GI bleed from other causes (gastritis, PUD, portal hypertensive gastropathy)
  • Treating individuals with HCV who are actively using drugs is part of the End Hep C SF Initiative! Patients should be counseled about the risk of re-infection
  • There are 5 reasons a cirrhotic will have worsening hepatic encephalopathy: increased gut protein load, infection, drugs, azotemia, or hypokalemia


Physical Exam in cirrhosis

  • Spider angiomata: the number and size of spider angiomata correlate with the severity of liver disease
  • Nail findings
    • Muehrcke nails = horizontal white bands
    • Terry’s nails = proximal 2/3 of the nail bed is white and distal 1/3 of nail bed is red
      • This is different from half-and-half nails seen in renal failure where the proximal 1/2 of the nail bed is white and the distal 1/2 of the nail bed is red
    • Both are due to hypoalbuminemia
  • Per Dr. Cello: A cirrhotic liver from alcohol is often big and feels like cooked ham whereas a cirrhotic liver from viral causes is often small and not palpable below the costal margin

Treatment of Varices

  • Pre-primary prophylaxis: Preventing variceal bleed by preventing varices.
    • Current goal is to treat underlying cause of cirrhosis leading to portal hypertension.  There is no data suggesting beta-blockers can prevent the developemnt of varices
    • We should continue screen patients with cirrhosis for varices
  • Primary prophylaxis: Preventing variceal bleeding by treating varices
    • Can treat with beta-blockers or endoscopic variceal ligation. Studies have shown similar efficacy
  • Beta-blockers reduce portal hypertension by decreasing portal venous inflow
  • Variceal ligation should be repeated until the varices are obliterated.  After they are obliterated they have a low risk of re-bleeding.


Treating HCV in IVDU

  • If the goal is to eliminate HCV then we need to treat the population most affected
  • Studies have shown successful (~95%) sustained virologic response in individuals treated with the direct-acting antivirals even when actively using drugs.
  • After treatment positive antibodies do not project against from re-infection
  • Reinfection rates in perviously cured individuals using drugs are ~5-10 per 100 person-years
  • SFDPH is actively treating individuals using drugs as part of their End Hep C SF Initiative


5 causes to look out for in a patient with hepatic encephalopathy

  • Protein load in the gut either from diet but more commonly from GI bleed
  • Infection
  • Drugs – especially drugs that have their first pass through the liver such as benzos
  • Azotemia
  • Hypokalemia worsening uremia




Moffitt Pearls 10.2.17 – Upper GI Bleed

Key Pearls for Upper GI Bleed Evaluation and Management

  • JAMA Rational Clinical Exam series: Does this patient have a severe upper GI bleed? A great resource for evaluation of a patient with suspected upper GI bleed attached below!
  • Bleeding sources proximal to the ligament of Treitz are considered Upper GI bleeds by definition

-> Top 3 causes include peptic ulcer bleed, gastritis and variceal bleed.

  • NG lavage with blood or coffee grounds has a positive LR of 9.6 for UGIB, but sensitivity is only 44%! If it’s there, you’re likely dealing with UGIB, but if it’s not, you still might be!
  • The other features that have solid likelihood ratios for UGIB are melena on exam (LR, 25) and BUN/Cr ratio >30 (LR, 7.5).
  • Blood clots in the stool make UGIB much less likely (LR 0.05).
  • The Blatchford prediction score efficiently identifies patients who do NOT need urgent scope. Score components are HR, BP, hgb, BUN, melena, syncope (as in our patient today), liver disease, and heart failure.
  • Remember: We usually use a transfusion threshold of hgb 7.0, but if someone is unstable and actively bleeding, transfuse regardless of hgb level!


VA Ambulatory Report Pearls 9.6.17 – Drug Induced Liver Injury

LT Pearls from the daily ditty about bacterial meningitis

  • Listeria meningitis is the one cause of bacterial meningitis that can have a lymphocytic predominant pleocytosis
    • CSF findings in Listeria meningitis can range from 100% PMNs to 100% monocytes

Thank you to Colin for presenting a patient seen in liver clinic with a history of alcoholic cirrhosis who recently stopped drinking found to have hepatocellular injury likely due to Disulfiram.

Learning Pearls:

  • DILI can be due to many different medications. To help you narrow your list, focus on the pattern of injury (hepatocellular vs. cholestatic) and the time course (acute vs. chronic)
  • Disulfiram can cause an acute hepatocellular injury and should be used with caution and monitoring in patients with a cirrhosis
  • In patients with cirrhosis with thrombocytopenia without anemia consider other sites of Epo production such as in HCC
  • First line medication assisted treatment for alcohol use disorder include Naltrexone, Acamprosate, and Disulfiram. Choose a medication based on patient goals and side effect profile.


Drug Induced Liver Injury (DILI)

  • Presentation
    • Depending on the offending agent:
      • Can see acute (< 3 months) or chronic liver injury (>3 months) dependi
      • Can see hepatocellular injury or cholestatic injury
    • Symptoms can vary based on severity of injury and pattern of injury
      • Patients are often asymptomatic
      • Can have non-specific symptoms including nausea, malaise, anorexia,
      • Can also cause present with symptoms similar to other causes of acute or chronic liver injury such as jaundice, pruritus, dark urine, pale stools
    • Diagnosis
      • Clinical diagnosis which can be hard to make
        • Known offending medication started prior to laboratory abnormalities
        • Stopping the offending agent leads to improvement in liver injury
        • Negative work-up for other causes
          • Assessment of other causes should be guided by history, physical exam, labs
        • If still uncertain the patient may need a liver biopsy
  • Medications that can cause DILI
    • There are over 1000 known medications and supplements that can cause DILI
    • Most common: Acetaminophen followed by antibiotics
    • Use the pattern and time course of liver injury to help you narrow your list of offending agents
    • Great resource for medications and supplements that can cause liver injury by the NIH:
  • Disulfiram induced liver injury
    • Seen within 2-12 weeks of starting Disulfiram
    • Disease severity can range from asymptomatic elevations in aminotransferases to acute liver failure and death
    • Can have immuno-allergenic fevers with fever, eosinophilia and rash
    • No hepatic dose adjustment for patients with liver failure but should be used with caution and should monitor for hepatotoxicity


Lab abnormalities in cirrhosis

  • Pearl from LT: In patients with cirrhosis who have a thrombocytopenia with a normal hemoglobin think about Epo production from sites other than bone marrow (such as in HCC)
  • The classic LFT pattern in patients with alcoholic cirrhosis of AST:ALT of >2 is often maintained when there is another acute insult not related to alcohol
    • There is a hypothesis that the AST:ALT ratio in alcoholic use is due to a deficiency of  pyridoxal 5′-phosphate in alcoholics, a cofactor for the enzymatic activity of ALT.  This may explain why the pattern is maintained when there is a separate liver insult.
  • Shoutout to Rabih for these awesome pearls about patterns of LFT abnormalities.


Medications for Alcohol Use Disorder (AUD)

Medication Mechanism of Action Adverse drug effects and contraindications Evidence Who should I use this in?
Oral Naltrexone Blocks of the mu-opioid receptor involved in the rewarding effects of drinking ADE:




ALT or AST > 150s

Use of Opiates

Reduces relapse to heavy drinking (See 1, 2)


Reduces alcohol consumption compared to placebo

Helpful in reducing the amount of alcohol


Less effective for abstinence

Depot Naltrexone (Vivitrol) Same as above, but long acting requiring monthly IM injection Same as above Decreased rate of heavy alcohol use


Increased the number of abstinent days

If covered by insurance and patient prefers long acting form
Acamprosate Acts at GABA and glutamate neutrotransmitters –> reduce symptoms of protracted abstinence Three times daily dosing


Safe to use in patients with liver failure


Renal dose adjustment required


Contraindicated in renal failure

Increased proportion of heavy drinkers who maintained abstinence in European study


Not demonstrated in these two US studies

Consider if the goal if abstinence and patient cannot tolerate other medication options
Disulfiram Inhibits aldehyde dehydrogenase –> accumulation of  acetaldehyde –> flushing, nausea, palpitations, headache  if alcohol is consumed Contraindicated in severe heart failure or CAD


Avoid in pregnant or nursing women


Monitor for hepatotoxicity

Most studies have shown it to be no more effective than placebo in maintaining abstinence, but may reduce drinking days


Most effective when given in monitored setting such as by spouse (27)

Patients highly motivated to have complete abstinence


Patients can use periodically for high risk social situations

Topiramate Acts at propionic acid, GABA and glutamate receptors SE: Cognitive impairment, weight loss, headache, depression.


Off label use


Titrate gradually over several weeks

Decreased consumption in patients with SUD, similar effect as naltrexone Off label use, second line medication
Gabapentin Structurally related to GABA SE: Sedation and dizziness


Abuse potential

Higher abstinence rates and decreased alcohol consumption in small trials Off label use, second line medication
Baclofen   SE: nausea, vertigo, sleepiness


Generally well tolerated

Mixed results Limited evidence of efficacy, off label use
Nalmefene Opioid antagonist SE: nausea, insomnia, fatigue, psychiatric symptoms





Taken as needed shown to reduce number of heavy drinking days Not available in the US
SSRIs Inhibits breakdown to serotonin   Reduced alcohol intake in patients with depression and alcohol use No efficacy demonstrated in patients without depression
Ondansetron 5-HT3 receptor antagonist SE: diarrhea, headache



Some demonstrated effectiveness in subgroups: early onset alcohol use and patients with specific genetic variant of 5-HT3 receptor Off label use, only demonstrated efficacy in sub-groups


The VA has lots of resources for patients with substance use disorders including: PES, Addiction consult, OTOP, and inpatient rehab.

Check out the California Society of Addiction Medicine’s guide for primary care physicians regarding patients who drink too much.


Moffitt Pearls – 8.11.17 – Saddle Nose Deformity, Upper GI Bleeding &Munchausen Syndrome

Thank you to HH and Neil for both presenting today! HH first presented a mini case of a patient who came in for a gout flare that was found to have a saddle nose deformity.

Neil then presented the interesting case of a young woman with a hx of gastric ulcers presented with epigastric pain and hematemesis who after extensive work-up including CT and EGD was found to have Munchausen syndrome!************************************************************************************

Key Pearls

  1. The differential diagnosis for saddle nose deformity falls into the classic triad of infectious, inflammatory and malignancy per table below.
  2. 80% of upper GU bleeds are due to four causes: peptic ulcer disease (35%), esophagogastric varices (30%), esophagitis (10%) and Mallory-Weiss tears (~5%).
  3. The management strategy for a pt. w/ munchausen syndrome is VERY difficult, but should include a single provider (w/ help from psychiatry) and goal to limit interventions + discuss diagnosis with patient in a supportive manner.


Differential Diagnosis for Saddle Nose Deformities

Infectious Inflammatory Malignancy Other
Syphilis GCA (formerly Wegner’s) NK T-cell Lymphoma Trauma
Leprosy Sarcoidosis Locally invasive tumor (BCC) Cocaine
TB Relapsing polychondritis Lymphomatoid Granulomatosis Surgery
Cutaneous Leishmaniosis      
Septal abscess      

 Differential Diagnosis for Hematemesis AND Fever

  • Mallory-Weiss Tear
  • Peptic ulcer bleeds c/b perforation
  • Hemosuccus pancreaticus (pseudoaneurysm/aneurysm)
  • Upper GI Malignancy – hemobilia, widespread esophageal/gastric malignancy

Munchausen Syndrome or Factitious d/o Imposed on Self

  • Definition: Falsified general medical or psychiatric symptoms
  • Risk Factors: Females, Unmarried, Healthcare professional
  • Diagnostic Criteria (DSM-5):
  1. Falsification of physical or psychological signs or symptoms, or induction of injury or disease, associated with identified deception
  2. The individual presents himself or herself to others as ill, impaired, or injured
  3. The deceptive behavior is evident even in the absence of obvious external rewards
  4. The behavior is not better explained by another mental disorder, such as delusional disorder or another psychotic disorderPrognosis: Very poor even as multiple studies have shown limited benefit even with psychotherapy
  • Management: One provider should oversee pt with help of psychiatry w/ goal to limit interventions. One should be sure to exclude all possible medical conditions and then discuss diagnosis w/ pt in supportive manner


Moffitt Pearls 7.5.17 – Wilson’s Disease & Hemolytic Anemia

Thank you to Vincent for presenting a challenging case of a young woman with anxiety and depression presenting with unexplained jaundice and cirrhosis, later representing with a severe, hemolytic anemia. Although similar to a prior case presented last month then this was a second presentation of possible Wilson’s disease

 Top Pearls:

  1. Acute alcoholic hepatitis is a chronic disease (despite the name!). Presentation is based on predominantly cumulative burden – a single binge in a patient with otherwise minimal alcohol intake is unlikely to cause severe alcoholic hepatitis.
  2. In a young patient (< 35 yo) with new diagnosis of cirrhosis, consider genetic causes including Wilson’s, hemochromatosis, alpha-1 antitrypsin disease, autoimmune hepatitis, PBC, PSC. Vascular disease and infectious hepatitis should also be considered.
  3. The combination of liver disease and hemolysis raises concern for Wilsonian Crisis, which can herald impending acute liver failure.

Laboratory Diagnosis of Tumor Lysis Syndrome

Alcoholic Hepatitis

The clinical syndrome of acute alcoholic hepatitis includes the following compilation of laboratory and clinical features:

  • Moderately elevated transaminases in a 2:1 ratio of AST/ALT
  • Typically less than 300, rarely greater than 500
  • Elevated bilirubin and Jaundice
  • Jaundice generally develops within 3 months prior to presentation
  • Fever & Neutrophilic Leukocytosis
  • Both should only be ascribed to alcoholic hepatitis after ruling out infection!
  • Right upper quadrant pain – can often palpate tender hepatomegaly
  • Clinical history of chronic drinking with or without recent bing
  • It’s not uncommon that patients have actually decreased their drinking in the weeks-months preceding acute alc hep due to the onset of symptoms with alcohol intake.

See this RCT from NEJM regarding pentoxifylline vs. prednisolone for the treatment of alcoholic hepatitis. Bottom line:  Acute alcoholic hepatitis is a profoundly morbid disease with very high mortality (30-40% in 6 months).  Prednisolone was associated with a reduction in 28-day mortality, but did not reach significance and there were no improvements in 90-day or 1 year mortality.

Autoantibodies Associated with Causes of Cirrhosis


Autoimmune hepatitis

IgG, ANA, antismooth muscle Ab, anti-liver-kidney microsome-1 Ab, anti-liver cytosol Ab-1

Primary biliary cirrhosis

ANA, anti-mitochondrial Ab

Primary sclerosing cholangitis

IgM (40-50%), p-ANCA (30-80%)

Wilson Disease (WD) & Hemolytic Anemia

  • Wilson’s disease (WD) is an inherent disease, caused by mutations in the ATP7B gene leading to decreased excretion of copper into the bile
  • Copper accumulation results in injury to the liver and the central nervous system (thank you Muazzum for you amazing neuro ROS)
  • WD presents in a fulminant form with hepatocellular dysfunction, hemolysis and various multiorgan failures (Wilson’s crises)
  • Wilson disease can cause a Coombs-negative hemolytic anemia WITHOUT schistocytes reported in the literature
  • The exact mechanism of the haemolytic process has yet to be defined. copper inhibits sodium potassium ATPase in the erythrocyte leading to haemolysis (and likely without schistocytes as in this case).
  • Medical treatment includes chelating agents and/or zinc, but these have not proved effective in fulminant liver failure, where only liver transplantation (LTx) is regarded as lifesaving.
  • Some limited data for plasmapheresis for rapid copper removal
  • Portends very poor prognosis, often leading to acute liver failure

 (see attached an article on a review of Wilson’s and Hemolytic anemia compliments of HH!!)

Blast from the past!!! Approach to Hemolytic Anemia (thank you Katie!!)

ZSFG Morning Report 6/9/2017: Hematochezia, Massive Transfusion Protocols and Narcan

Thank you to Malia Honda and Brad Hunter for presenting a case from 5R of a middle aged man, who presented after PEA arrest and then had massive hematochezia requiring massive transfusion protocol.

Top Learning Pearls

  1. Narcan (naloxone), is the opioid antagonist used in opioid overdose. Rarely it can cause pulmonary edema through both cardiogenic and noncardiogenic mechanisms.
  2. BUN/Cr ratio can help determine location of GI bleed, if >20 is more likely to be upper GI source.
  3. Activate massive transfusion protocol when you need blood quickly for hemodynamically unstable patient. MTP will provide blood products in appropriate ratio (pRBC:FFP:plts). Rule of thumb to call for MTP if >4 u of prbc in one hour.



-Narcan can be delivered in many routes and doses (intranasal, IV, IM, subQ, inhalation).

  • Intranasal narcan prescribed to outpatients usually contains 2 or 4 mg.
  • IV/IM/SubQ: Initial 0.4mg to 2mg, and can be repeated
  • For reversal of respiratory depression with therapeutic opioid dose, more in the realm of 0.02 to 0.2mg IV to prevent severe withdrawal

-Incidence of Naloxone-Related Pulmonary Edema is overall low, thought to be between 0.2 – 3.6% of pts who receive narcan for overdose. The mechanisms of for pulmonary edema are thought to be both cardiogenic and noncardiogenic pulmonary edema, d/t the effect on cardiovascular tone from a resultant catecholamine surge, as well as increased pulmonary capillary leak.

Check out these two sources for some more information on narcan-related pulmonary edema


GI Bleeds in patient with cirrhosis

We are familiar with esophageal variceal bleeding, but Dr. Cello reminded us there are many sites where varices/collaterals occur at splanchic-systemic junctions, which all have a theoretical risk of bleeding, including

  • gastric vein + esophageal veins –> gastric varices
  • superior rectal vein + inferior rectal veins –> rectal varices
  • duodenal varices
  • jejunoileal varices
  • colonic and rectal varices
  • Paraumbilical veins + subcutaneous veins in anterior abdominal wall –> caput medusa

LABS to pay attention to in a GI Bleed:

  • -BUN/Cr ratio: if greater than 20 suggests UGIB, as blood is readily absorbed pre-jejunum, and broken down. As opposed to Lower GI bleed where the BUN/Cr ratio is normal
  • -Hemoglobin/hematocrit: Remember that acute blood loss is not reflected in hemoglobin/hematocrit! Take a GI bleed seriously even when H/H are normal, and pay attention to vitals and the clinical picture. Hemoglobin represents a concentration, so starts going down when we give IVF or when the body increases its intravascular plasma concentration.

Dr. Cello also made the good point that in a middle aged patient with LGIB, it is critical to do an anorectal exam to investigate for any anorectal masses. Remember to include malignancy on your differential for bleeding sources!


VA Intern Report Pearls 6.8.17: Behcet’s and the Silk Road

Case summary

Thanks to Colin Purmal for presenting the case of a 26F presenting with diffuse abdominal pain, bloody diarrhea and oral ulcers, who was diagnosed with Behcet’s disease.

Top pearls

1. Oral ulcers have a fascinating differential, including infection, autoimmune disease, malignancy, medication-induced, and vitamin deficiencies. But the most common cause is the aphthous ulcer!

2. Consider treating severe infectious bloody diarrhea (e.g. systemically ill, immunocompromised or elderly) with ciprofloxacin. The benefits outweigh the risks except in cases with high concern for EHEC or Salmonella typhi.

3. Behcet’s disease is a key “Crohn’s disease mimicker.”

Oral ulcers

  • Pocket reference Ddx:

Infection– primary HSV, HIV,TB, CMV, EBV, coxsackie, GC/CT, syphilis, fungal

Autoimmune– Behcet’s, SLE, Crohn’s, blistering skin disease (Pemphigus)

Malignant– SCC, lymphoma



Vit Deficiencies

Antibiotics in infectious bloody diarrhea

  • Most acute infectious diarrhea does not require antibiotic therapy.
  • 2001 IDSA guidelines for dysentery (to use the Oregon Trail-approved terminology) recommend obtaining stool cultures and treating empirically for 3 days in 3 cases: 1) toxic-appearing, 2) elderly, 3) immunocompromise.
  • The main benefit of antibiotic therapy is reduced duration of symptoms.
  • Ciprofloxacin is first-line, but Azithromycin can be used in pregnancy or if high suspicion for resistant Campylobacter (e.g. recent SE Asia travel).
  • Contraindications: 1) high concern for enterohemorrhagic E. coli (concern for precipitating HUS), 2) high concern for Salmonella typhi (concern for promoting carrier state and relapse)

IDSA Guidelines:

Crohn’s disease mimickers

  • Thinking about Crohn’s disease?
  • Consider Behcet’s disease in…patients from eastern Asia or the Middle East (the Silk Road!) with oral ulcerations (more frequent and more severe); genital ulcerations (more specific but less sensitive); systemic symptoms, including ocular symptoms, rashes, pan-vasculitis, weird clots (Budd-Chiari or cerebral venous thrombosis), pathergy (a 20G needle prick causes a papule or pustule within 48 hours).
  • International Study Group for Behcet’s Disease Diagnostic Criteria:
Recurrent oral ulceration: Aphthous (idiopathic) ulceration, observed by physician or patient, with at least three episodes in any 12-month period
Plus any 2 of the following:  
Recurrent genital ulceration Aphthous ulceration or scarring, observed by physician or patient
Eye lesions Anterior or posterior uveitis cells in vitreous in slit-lamp examination; or retinal vasculitis documented by ophthalmologist
Skin lesions Erythema nodosum-like lesions observed by physician or patient; papulopustular skin lesions or pseudofolliculitis with characteristic acnelform nodules observed by physician
Pathergy test Interpreted at 24 to 48 hours by physician

Behcet’s review: