Although I was unable to attend this year’s liver symposium at NASPGHAN19, I reviewed the lecture notes. There is some terrific content. Here are some of the slides (borrowed with permission from NASPGHAN).
Link to complete NASPGHAN Chronic Liver Disease Symposium 2019
SESSION II – FRONTIERS IN LIVER THERAPEUTICS
Keynote Speaker: Outcomes for the future: How do we improve on the status quo? Ronald J. Sokol, MD, FAASLD, Children’s Hospital Colorado (SLIDES NOT AVAILABLE in onliine handout)
Recognition and stabilization of the pediatric patient with acute liver failure Robert Squires MD Children’s Hospital of Pittsburgh at UPMC
Should I offer treatment for my patients with Hepatitis B or Hepatitis C? Regino P. Gonzalez-Peralta MD, AdventHealth for Children
Are there any medical therapies for NASH? Marialena Mouzaki, MD, Cincinnati Children’s Hospital Medical Center
This lecture describes a lot of the emerging pharmacologic treatments; none of these are currently recommended.
P Rosenthal et al. Hepatology 2019; 69: 2326-37. This study examined the efficacy and safety of combined entecavir and Peginterferon for immune-tolerant chronic hepatitis B-infected children (n=60). 48 weeks after completing treatment (week 96), 2 children (3%) achieved the primary outcome of undetectable HBeAg with HBV DNA levels <1000 IU/mL. These two children were also HBsAg negative/anti-HBs positive. In the other children (55 completed study), the ALT and HBV DNA levels were similar to baseline. 37 children experienced adverse events. My take: Entecavir/peginterferon is not very effective in immune-tolerant children infected with chronic HBV.
DL Thomas. NEJM 2019; 380: 2041-50. This article reviews the pathway to the global elimination of chronic hepatitis. Currently, it is estimated that hepatitis C virus (HCV) and hepatitis B virus (HBV) kill more than 1 million persons each year. “In fact, by 2040, deaths from chronic hepatitis are projected to exceed the combined mortality associated with HIV infection, tuberculosis, and malaria.”
JR Dillman et al. J Pediatr 2019; 212: 60-5. This study with 41 patients and 13 patients with biliary atresia prospectively assessed ultrasound shear wave elastography (SWE). The authors found that SWE with a cut-off value of >1.84 m/s had 92% sensitivity and 79% specificity. Also, in their cohort, GGT >320 had a sensitivity of 100% and specificity of 78%.
Z Younossi et al. Hepatology 2019; 69: 2672-82. This review provides a global perspective of NAFLD. 25% of the world’s population is currently thought to have NAFLD with highest prevalence in South America at 30.45% and lowest in Africa at 13.5%. This article usggest North America to have 24.1% prevalence rate.
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
A recent study (WJ Jeng et al. Hepatology 2018; 68: 425-34) indicates that many patients with Hepatitis B e Antigen-Negative Chronic Hepatitis B benefit from a finite treatment with oral antivirals.
These findings are discussed by P Lampertico and T Berg (editorial 397-400). In the Jeng study, the investigators prospectively followed the effect of antiviral cessation in 691 individuals after patients had undetectable HBV DNA and met Asian Pacific Association for the Study of Liver guidelines for stopping. HBsAg clearance occurred in 13% who discontinued therapy compared to 3% during nucleos(t)ide treatment. The authors note that virologic relapse occurred in 79% and that the immune system activation driven by clinical relapse can be beneficial in yielding a cure. Clinical decompensation was infrequent and most could be retreated; three patients with cirrhosis and decompensation died
My take: These studies show that in carefully-selected and carefully-monitored patients with HBeAg-negative chronic hepatitis B infection, it is feasible to successfully stop oral antiviral therapy.
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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. 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.
A recent prospective study (C-J Liu et al. Gastroenterol 2018; 154: 989-97) provided some reassurance about the likelihood of hepatitis B virus (HBV) reactivation during hepatitis C virus (HCV) treatment with direct-acting antivirals (DAA).
In this study with 111 patients with both HCV and HBV treated with ledpasvir/sofusbuvir, all (100%) of the patients had a sustained virologic response for their HCV infection. Other key findings:
- Of the 37 patients with baseline HBV DNA < 20 IU.mL, 31 (84%) developed detectable HBV DNA levels through posttreatment week 12.
- Of the 74 patients with baseline HBV DNA >20 IU/mL, 39 (53%) developed increases in HBV DNA >1 log10 IU/mL through posttreatment week 12.
- 5 patients developed ALT >2 times ULN and 3 patients were started on HBV therapy.
The associated editorial (pgs 795-8) made the following recommendations:
- “HBsAg-negative/HBcAb-positive patients should be monitored with ALT alone until SVR12 and should be tested with HBsAg +/- HBV DNA only if ALT increases or fails to normalize on therapy.”
- “HBsAg-positive patients with undetectable baseline HBV DNA should be considered for preemptive anti-HBV treatment, or monitored with ALT and HBV DNA until SVR12”
- “HBsAg-positive patients with positive baseline HBV DNA should be started on preemptive anti-HBV treatment until SVR12.”
Using the above management strategy will limit the number of HBV-infected patients who need to be treated.
My take: This study and the associated editorial provide useful information regarding DAA in coinfected HBV/HCV patients; this is important for patients and practitioners, especially given the black box warning on DAA medications.
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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.
A brief report (KW Cheung et al. Clin Gastroenterol Hepatol 2018; 16: 144-5) describes a prospective multicenter study (2014-16) in Hong Kong which examined immunoprophylaxis failure (IF) of infants (n=654) born to mothers infected with hepatitis B virus (HBV) infection. All infants had received HBV vaccine and HBV immunoglobulin (within 12 hours of birth). Maternal HBV DNA & serology was measured at 28-30 weeks.
- There were 7 cases of IF (1.1%). All were born to women with positive HBeAg and HBV DNA >8 log10 copies/mL (>17 million IU/mL)
- The authors note that “although a cutoff of 200,000 IU/mL (~6 log10 copies/mL) has been recommend, the optimal viral load cutoff to initiate HBV antiviral treatment remains debatable.”
My take: HBV prophylaxis with HBV vaccination and HBIG is very effective. However, HBV DNA levels can be used to target HBV antiviral treatment to further minimize the chance of IF failure.
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The ability to determine if a patient has cirrhosis/severe fibrosis with a noninvasive test can help determine appropriate monitoring and treatment for many liver conditions. As such the AGA has provided recommendations for the use of vibration-controlled transient elastography (VCTE).
- JK Lim et al. Gastroenterol 2017; 152: 1536-43.
- S Singh et al. Gastroenterol 2017; 152: 1544-77.
Many recommendations are based on the specific unit of measurement, kilopascals (kPa)
Specific recommendations (most with low or very low quality evidence):
- “In adults with chronic HCV, we can accurately diagnosis cirrhosis …with VCTE-defined liver stiffness of ≥12.5 (±1) kPa.” The AGA suggests using VCTE rather than MRE for detection of cirrhosis.
- “In adults with chronic HCV who have achieved SVR…we can accurately rule out advanced fibrosis (F3 and F4) with post-treatment VCTE-..of ≤9.5 (±1) kPa.” . Even in patients who have had HCV eradicated, if cirrhosis has been identified, careful followup is recommended.
- “In adults with chronic HBV, we can accurately diagnosis cirrhosis…with VCTE…of ≥11.0 (±1) kPa.”
- “The AGA makes no recommendation regarding the role of VCTE in the diagnosis of cirrhosis in adults with NAFLD.” For NAFLD, VCTE is not as helpful as with chronic HCV and HBV. Currently, liver biopsy remains the “gold standard.” However, for noninvasive imaging, “the AGA suggest using MRE, rather than VCTE, for detection of cirrhosis.
- For adults with suspected compensated cirrhosis, a VCTE of 19.5 or greater can be used “to assess the need for esophagogastroduodenoscopy to identify high risk esophageal varices.”
My take: These elastography recommendations are applicable for adults. For pediatric patients, these reports suggest that elastography may be helpful in specific circumstances as well.