Liver Briefs -June 2019

YH Yeo et al. Hepatology 2019; 69: 1385-97.  The prevalence of high risk individuals in the U.S. who are susceptible (not immune) to hepatitis B has decreased from 83% to 69% from 2003 to 2014.  That still leaves 64 million who would benefit from HBV vaccination.

M Sharma et al. Hepatology 2019; 69: 1657-75. This meta-analysis compared therapies for primary prevention of esophageal varices and concluded that nonselective beta-blocker (NSBB) monotherapy may decrease all-cause mortality and carried a lower risk of serious complications than variceal band ligation (VBL). However, the commentary (1382-84 by L Laine) reaches a different conclusion. “Current recommendations for primary prevention with VBL or NSBB or carvediolo still appear to be acceptable…using a shared decision-making approach” to weigh issue such as daily medication or periodic endoscopy.

J Nguyen et al. J Pediatr 2019; 207: 90-6. This study modeled the cost-effectiveness of early treatment with direct-acting antiviral therapy in adolescents with hepatitis C infection.  With pangenotypic agenst, the cost would be $10000 to $21000 per QALY gained.

S Trinh et al. Clin Gastroenterol Hepatol 2019; 17: 948-56. This retrospective hepatitis B study examined the changes in renal function between 239 tenofovir disoproxil fumarte (TDF) treated patients and 171 entecavir treated patients.  Key finding: TDF was not associated with higher risk of worsening renal function in this cohort with a mean followup of 43-46 months in patients with baseline normal renal function.  In patients with renal impairment, deterioration of renal function was noted in TDF-treated patients.  Thus, TDF should be avoided in patients with impaired renal function.


Rhododendrom in Sandy Springs


“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

What is the role for preventing variceal bleeding in Biliary Atresia?

During medical school, I read a book called “The House of God”  (The House of God – Wikipedia, the free encyclopedia.  One of this cynical book’s premises is that doing more diagnostic tests and treatments to help patients actually harms them.

A recent study of children with biliary atresia reminded me of this premise (Gastroenterol 2013; 145: 801-7, eidtorial 719-22).   In this retrospective study, there were 66 children with endoscopic evidence of portal hypertension who underwent endoscopic therapy for either primary (n=36, mean age 22 months) or secondary (n=30, mean age 24 months) treatment of esophageal varices biliary atresia (2001-2011).  These children were at high risk for bleeding; they had a mean bilirubin of >10 mg/dL and 20% had ascites.


Primary prophylaxis group: mean of 4.2 sessions were needed to eradicate varices.  Varices reappeared in 37%; there was no breakthrough bleeding.  97% survived for 3 years.  All of these patients had varices grade 2 or higher and 94% had red wale markings.

Secondary prophylaxis group (after previous bleeding): mean of 4.6 sessions to eradicate varices.  Varices reappeared in 45% and 10% had breakthrough bleeding.  84% survived for 3 years.


  • For bleeding group, sclerotherapy was used in 73%, banding in 17%, and both in 10%.
  •  For prophylaxis group, sclerotherapy was used in 44%, banding in 41%, and both in 14%.
  • By the end of the study, sclerotherapy was mainly used in patients weighing less than 8 kg.
  • Each endoscopy session had the same endoscopist, used octreotide (2 mcg/kg/hr) an 1 hour before and then for 2-3 days afterwards.
  • With bleeding patients, these sessions occurred after the patient was stabilized, with a mean of 10 days afterwards.
  • Patients had an average of four 3-day hospitalizations.
  • Within an average of 14 months, more than half of the primary prophylaxis group had undergone transplantation

The authors interpret their data as follows:  “primary or secondary prophylaxis of bleeding is well tolerated and greatly reduces the risks of variceal bleeding in children with biliary atresia and high-risk gastroesophageal varices.  The results support the active detection of these signs by endoscopic procedures.”

In contrast, the editorial is much less supportive of primary prophylaxis.  “We need to weigh the risks and benefits of multiple procedures in a nonbleeding child who may not bleed for years, when varices have a high chance of recurring and transplant is sometimes imminent. Because mortality from gastrointestinal bleeding in children is quite low (zero in this small study), we may need to consider a ‘wait and see’ approach.”

Bottomline: A failed Kasai is an indication for transplantation which is a much more definitive treatment for portal hypertension.

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