Liver Briefs May 2017

Briefly noted:

O Jeanniard-Malet et al. JPGN 2017; 64: 524-7. This survey of 28 centers in France assessed clinical practice with regard to primary prophylaxis in portal hypertension. More than 75% use endoscopy to screen for varices in patients with chronic liver conditions. “In cases of grade 2 varices with red marks and grade 3 varices >90% of centres perform sclerotherapy or endoscopic variceal ligation.”

Y-D Ren et al. Hepatology 2017; 65: 1765-8. FMT for chronic HBV? This small study with 5 patients who received fecal microbiota transplantation in an effort to clear HBeAg.  There were 13 controls.  Patients in both group received either ongoing entecavir or tenofovir antiviral therapy (& had received for at least 3 years). FMT was given every 4 weeks (1 to 7 treatments). HBeAg declined gradually after each round.  Three patients in the FMT arm cleared HBeAg compared with none in the control arm.  Two of the three cleared HBeAg after on FMT and the third after two rounds of FMT.

Y Sun et al. Hepatology 2017; 65: 1438-50.  In this report, the authors propose to augment the liver biopsy classification in patients with Hepatitis B.  Their goal is to provide more information about dynamic changes regarding fibrosis using three terms:

  • Predominantly progressive: thick/broad/loose/pale septa with inflammation
  • Predominantly regressive: delicate/thin/dense/splitting septa
  • Indeteminate

Using this new designation, they characterized 71 paired liver biopsies before and after entecavir for 78 weeks.  Before treatment: 58%, 29%, and 13% for progressive, regressive and indeterminate; after treatment: 11%, 11%, and 78% respectively.

Rodin Museum, Gates of Hell


Cutting Edge for Endoscopic Control of Bleeding

A recent review elaborates on the newest methods for endoscopic control of bleeding. Topics included caplock clips, endoscopic suturing, and hemostatic sprays.

Full text: New Endoscopic Technologies and Procedureal Advances for Endoscopic Hemostasis (from Clinical Gastroenterology and Hepatology)

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Many Glacier Hotel

Many Glacier Hotel

Optimistic Results for Hepatitis C plus Hepatology Update

The August issue of Hepatology had several articles on Hepatitis C confirming the efficacy of newer agents:

  • LI Backus et al Hepatology 2016; 64: 405-14.  This “real-world” observational study from the VA Clinical registry with 4,365 genotype 1 treatment-naive patients who received ledipasvir/sofosbuvir showed SVR rates of 91.3% (w/o ribavirin) and 92% (w ribavirin).
  • P Kwo et al. Hepatology 2016; 64: 370-80 (OPTIMIST-1) This study showed that 12 weeks of simeprevir+sofusbuvir for 12 weeks was highly effective (97% SVR) and that 8 weeks of this therapy was inferior (83% SVR).  N=310 with genotype 1 (w/o cirrhosis).  No patients stopped therapy due to adverse effects.
  • E Lawitz et al. Hepatology 2016; 64: 360-69 (OPTIMIST-2) This study showed that simeprevir+sofusbuvir for 12 weeks was effective in genotype 1 patients (n=103) with cirrhosis.  For treatment-naive, the SVR was 88% and for treatment-experienced patients, the SVR was 79%.

Also in Hepatology:

  • S Heibani et al Hepatology 2016; 64: 549-55. This study looked at 1-week versus 2-week intervals for endoscopic ligation.  While 1-week ligation eradicated varices more quickly, neither approach was associated with differences in number of endoscopies, complications (including rebleeding) or other clinical outcomes.
From earlier study of "real-world" treatment of Genotype 1. Gastroenterol 2016; 150: 419-29.

From earlier study of “real-world” treatment of Genotype 1. Gastroenterol 2016; 150: 419-29. (Full text link)


“Cat in the Hat” Effect with Transjugular Intrahepatic Portosystemic Shunt (TIPS)

IL Holster et al (Hepatology 2016; 63: 581-89) provide useful data on the use of transjugular portosystemic shunt (TIPS) compared with endoscopic therapy/Beta-blocker for prevention of variceal rebleeding.

In this multicenter randomized trial, TIPS was compared with either endoscopic variceal ligation or glue injection along with beta-blocker treatment in 72 patients with either a first or 2nd episode of variceal bleeding.  The median followup was 23 months.

Key findings:

  • 0 of 37 (0%) of TIPS patients had rebleeding compared with 10 of 35 (29%) in the endoscopic group.
  • TIPS mortality 32% compared with endoscopic group mortality of 26% (P=0.418)
  • Hepatic encephalopathy was 35% (TIPS) vs 14% (endoscopic group) (P=0.035)

This study shows that rebleeding is common in the endoscopic therapy group but that TIPS, while fixing bleeding, often resulted in other problems.  In “The Cat in the Hat” analogy, this would equate to moving the bathtub stain to the dress or curtains but not really improving the situation.

My take: It is helpful to see how these treatment strategies compare.  The data from this study does not clearly point to one strategy over another for dealing with this serious consequence of cirrhosis.

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Statue at Ferry Dock, Culebra

Statue at Ferry Dock, Culebra

Esophageal Varices and Primary Prophylaxis

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

One of the topics debated at this year’s meeting was the issue of whether it is worthwhile for patients with esophageal varices to undergo primary prophylaxis.

Here’s a summary:

Esophageal Banding: Proactive vs Expectant Waiting Maureen Jonas (Boston Children’s) and Karen Murray (Seattle Children’s)

Reviewed definitions of portal hypertension. Hepatic venous portal gradient (HVPG) >12 associated with variceal bleeding is the standard in adult medicine.

Management issues: primary prophylaxis, treatment of acute bleeding, and secondary prophylaxis.

Adult Data/Guidelines:

  • 1-year rate of first bleeding 5% for small varices and 15% for large varices
  • 1-year recurrent variceal bleeding ~60%
  • Compensated cirrhotics with small high-risk varices (or mod-large varices): consider treatment with beta-blocker (and/or EVL for mod-large varices).
  • Beta-blockers and EVL –similar efficacy and survival in adults.
  • Lowering HVPG by 20% lowers risk of complications
  • Beta-blockers stopped in ~20% of adults due to side effects like fatigue or shortness of breath.

Pediatrics and Beta-Blockers:

  • Beta-blockers have good safety in children in a wide range of conditions –cardiomyopathy, migraines, others. HVPG is used in adults but is very invasive.
  • Pediatric HVPG correlation to variceal development is not yet established.
  • Bleeding from varices –17-29% in biliary atresia (BA) patients over 10 years. Yearly rates: 2-9%.
  • Mortality in pediatrics from bleeding varices: 2-5% with BA, 0-2% with portal vein thrombosis.

Non-Selective Beta-blockers.

  • There are adverse effects: hypotension, bronchospasm, hypoglycemia. Am Gastroenterol 2014; 27: 20-6.  In infants/pediatric patients with shock, tachycardia is the primary response. Beta-blockers interfere with this.
  • In pediatric studies, bleeding risk has not been proven to be reduced with non-selective Beta-Blockers.

Risks of primary prophylaxis with banding or sclerotherapy:

  • Adverse effects: could convert a child not prone to bleeding into one prone to bleeding. Stricture possible.
  • Efficacy? Limited data.  Study on prophylactic sclerotherapy if grade 2/3. Median followup was only 1.7 years. JPGN 2012; 55:574
  • Sometimes cannot eradicate varices and/or recur quickly. Gastroenterol 2013; 145: 801.


  • Sometimes we have to extrapolate from adult data
  • Currently about half of pediatric GIs use primary prophylaxis in these cases (JPGN 2011; 52: 751)

Take-home message: insufficient data to demonstrate efficacy of primary prophylaxis as well as to demonstrate adverse effects of primary prophylaxis.

Related blog posts:

NASPGHAN Postgraduate Course 2014 -Endoscopy Module

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  Link to full syllabus:

PG Course Syllabus 2014

The Dreaded Wake-Up Call (Part A) –Maercedes Martinez (NY Presbyterian Hospital) (pg 55 syllabus)

Variceal Bleeding – “When RED is not attractive

Discussed presentation of varices (gastric/esophageal), etiologies, association with portal hypertension. Reviewed variceal grading.

Medical management:

  • PICU admit
  • Avoid over-transfuse (goal ~ 8 g/dL)
  • Correct coagulopathy
  • Role of platelets is controversial/if trouble with endoscopy, may be helpful
  • Suggested dosing for octreotide/somatostatin: 2 mcg/kg bolus then 1-2 mcg/kg/hr (typically max 100 mcg/hr), antibiotics
  • Most patients do not require emergency overnight endoscopy.
  • Sclerotherapy and banding reviewed -including complications.
  • Transjugular intrahepatic portosystemic shunts (TIPS) and Surgical options briefly discussed

The Dreaded Wake-Up Call (Part B) –Lee Bass (Children’s Hospital of Chicago) (pg 67 in syllabus)

Nonvariceal GI Bleeding Management

  • Start with ABCs -airway, breathing, cardiovascular –fluid resuscitation/blood products
  • Restrictive transfusion strategy (Hgb <7 as threshold) (Villanueva et al NEJM 2013) helpful for survival in adults
  • Treatment with PPI improves rates of high risk stigmata on endoscopy
  • Prokinetics can improve identication of bleeding lesions
  • Preparation for endoscopy is most important (slide on page 70 of syllabus)
  • Also on page 70, pictures of typical findings with GI bleeding: nonbleeding vessel, adherent clot, spurting blood, oozing blood, and flat pigmented spot and clean base
  • Endoscopic management -combination of two techniques appears to be more effective than single method. injection, thermal probe, hemoclips, hemospray (not available in U.S.

Endoscopic Interventions for Biliary Tract Disease — Victor Fox (pg 75 in Syllabus)

Choledocholithiasis is most common need for interventional biliary endoscopy and increasing related to increase risk with increase in obesity.(Buxbaum J. Gastrointest Clin N Am 2013;23:251‐75)

Requires advanced training to achieve high level of skill and experience

  • >200 cases needed to achieve selective cannulation required for interventions
  •  Acquisition and maintenance of skills by pediatricians is controversial

Other points:

  • No equipment is favorably designed for young or small children
  • Success and complication rates are similar as in adults (Varadarajulu S, et al. Gastrointest Endosc 2004;60:367)
  • Discussed biliary strictures (etiologies, management/stents), choledochocele, papillotomy, bile leak (Soukup ES et al. J Pediatr Surg 2014;49:345‐8)
  • “Most strictures and leaks can be successfully managed endoscopically without need for surgical intervention”

Take-home message: Endoscopic biliary interventions are increasingly employed in children with similar safety and technical success as adult patients

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.