C Sikavi et al. Hepatology 2018; 67: 847-57. This systematic review highlights that the combination of hepatitis C virus (HCV) infection and HIV infection is no longer a difficult-to-treat population with the implementation of direct-acting antivirals (DAAs). There are similar sustained virologic responses (SVRs) among those with and those without HIV. In clinical trials, patients with combined HCV-HIV had SVRs of 93.5-98% with DAA treatment; “real-world cohorts” had SVRs of 90.9%-98%.
MS Middleton et al. Hepatology 2018; 67: 858-72. Using data from the prospective CyNCh trial (cysteamine for NAFLD), the authors examined MRIs for diagnostic accuracy among 169 enrolled children. In this group, 110 (65%) and 83 (49%) had MRI and liver biopsy at baseline. MRI-PDFF (proton density fat fraction) was able to classify grade 1 steatosis from grade 2-3 steatosis with area under receiving operator characteristic curve of 0.87. Thus, this study shows MRI-estimated PDFF has high diagnostic accuracy.
G Mieli-Vergani et al. JPGN 2018; 66: 345-60. Position paper for Pediatric Autoimmune Liver Disease (AIH, ASC, de novo AIH after liver transplantation). This is a very useful review. A couple of pointers from the authors:
- “Present experience with budesonide as the first-line treatment is limited and does not appear to offer clear clinical advantage over the standard treatment”[prednisone]
- Fecal calprotectin should be obtained to evaluate for IBD in patients with autoimmune liver disease, “even in asymptomatic children.”
JM Cotter et al. JPGN 2018; 66: 227-33. This retrospective study with 39 patients with primary sclerosing cholangitis (PSC) showed a lack of correlation between liver tests and fibrosis at presentation. Average age of PSC diagnosis was 11.2 years, 74% had inflammatory bowel disease and 51% had autoimmune hepatitis. Related blog post: Big Pediatric PSC Study (with 781 children)
“Designing Tomorrow’s Vaccines” is a fascinating assessment of the success of vaccines as well as a look into the what future vaccines may accomplish (NEJM 2013; 368: 551-60).
First, I like the quote from Thomas Jefferson noted in the article:
“I avail myself of this occasion of rendering you a portion of the tribute of gratitude due to you from the whole human family. Medicine has never before produced any single improvement of such utility…mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated.” Letter to Edward Jenner (May 14, 1805).
Jefferson’s enthusiasm was not without merit. “In the 20th century alone, smallpox claimed an estimated 375 million lives.” Yet, “since 1978, not a single person has died from smallpox.” Unfortunately, at this time, every year “more than 1.5 million children (3 per minute) die from vaccine-preventable diseases.”
Previous success in the U.S: Comparison of the estimated number of cases per year in the 20th century with the number of deaths in the year 2002 from the same diseases:
- Poliomyelitis: 1.63 million vs 0
- Diptheria: 17.6 million vs 0
- Measles: 5.03 million vs 36
- Pertusis: 1.47 million vs 6632
- Rubella: 4.77 million vs 20
- Smallpox: 4.81 million vs 0
Despite these advances, vaccines have “yet to realize their full potential.” Effective vaccines are needed for malaria, HIV, and tuberculosis. Vaccines for influenza which rely on 50-year-old technology need to be improved.
So how can this be achieved?
- Improved knowledge of atomic structure/structural biology has provided new insights into neutralizing antibodies along with specific antibody reactions. This can counter immune evasion by targeting highly conserved regions
- Millions of gene sequences encoding antibodies within a single individual can be analyzed to improve vaccine design
- Genomewide sequencing of microbes has improved selection of vaccine targets
- Improvements in delivery systems, like using viruslike particles or nanoparticles; alternatively, gene-based delivery of vaccines is feasible
- Recombinant techniques has allowed a shift from egg-based methods
What is not on the horizon — a vaccine for the half-truths that permeate the discussion.
AAP recommends against breastfeeding infants of HIV-infected mothers:
“It is critical that physicians are aware of the HIV transmission risk from human milk and the current recommendations for feeding HIV-exposed infants in the United States. Because the only intervention to completely prevent HIV transmission via human milk is not to breastfeed, in the United States, where clean water and affordable replacement feeding are available, the American Academy of Pediatrics recommends that HIV-infected mothers not breastfeed their infants, regardless of maternal viral load and antiretroviral therapy.”
Thanks to Mike Hart for sharing this link.
Hepatitis C virus (HCV) now kills more people in the United States than HIV (Ann Intern Med 2012; 156: 271-78). Data from the CDC followed the mortality burden of Hepatitis B (HBV), HCV, and HIV from 1999 to 2007. The data were derived from death certificates & a limitation was that these are often completed by individuals other than the primary physician. Sometimes the exact cause is difficult to discern. However, this is more likely to result in underreports of deaths from viral hepatitis compared with those from HIV.
In total, 21.8 million death certificates were analyzed.
- HBV death rate stayed relatively constant –in 2007: 1815 deaths*
- HCV death rate increased steadily –in 2007: 15106 deaths*
- HIV death rate improved –in 2007: 12734 deaths*
*When infection was cause or underlying contributor of death
One in 33 baby boomers are infected with HCV; most do not know they are infected. Three-fourths of the deaths for HCV are in this age group as well. In addition, it is expected that mortality from HCV will grow over the next 10-15 years without a major intervention. http://www.ajc.com/health/hepatitis-c-deaths-up-1356460.html
Given the increasing HCV disease burden, this strengthens the rationale for more aggressive case finding and the use of more effective & more expensive therapies (see previous blog: The cost of progress in treating Hepatitis C. Among patients with HCV with advanced disease/cirrhosis, monitoring for HCC is important (Looking for trouble).
- -Hepatology 2011; 54: 1547. Excess mortality (6x gen population) in those who achieve SVR
- -Gastroenterology 2010; 138: 513. Predicts peak cirrhosis due to HCV in year 2020; peak HCV prevalence was year 2000.
- -Clin Gastro Hep 2010; 8: 924. Epidemiology 2010.
- -Hepatology 2010; 52: 1543. Visceral adiposity is associated with increased histological findings and higher viral loads.
- -Gastroenterology 2010; 138: 136. Predicting clinical outcomes: plt<99, Alb <3.5, AST/ALT ratio >1.2, & TB>2 all assoc with 40-50% risk of developing ‘clinical outcome’ in next 3.5yrs. Outcomes: ascites, variceal hemorrhage, decompensation according to CTP (66%), peritonitis, death (2%), encephalopathy
- -Hepatology 2009; 49: 729. 5-yr f/u after successful HCV RX, n=150. 2 developed HCC.
- -Gastroenterology 2009; 136: 138, 39(ed). HCC occurring c HCV ~1%/yr in HALT-C study. prolonged Rx -not helpful. n=1005
- -Hepatology 2008; 47: 1128. Increasing mortality of HCV between 1995-2004. Due to aging of infected individuals.
- -Hepatology 2008; 47: 1371. Genotype 4 review.
- -Hepatology 2008; 47: 836. 2/121 bx of children had cirrhosis.
- -J Pediatr 2007; 150: 168. n=60. Looked at two populations: look back after transfusion and referrals. mean age at infection 7 months, mean time with infection 13yrs. 12% developed significant fibrosis.
- -Hepatology 2007; 45: 1076. Large study: Lancet 2006; 368: 938. 39,109 c HBV, 75,834 c HCV, 2,604 c both. death rate: 3.2%, 5.3%, 7.1% respecively. Increased rate of dying c HCV due to drug use rather than liver dz.
- -Clin Gastro & Hep 2006; 4: 1190-1191, 1271-78, 1278-1282. slow progression of HCV in 184 untreated women infected in 1977 (mean 27 years) — 2.1% developed cirrhosis. genotype 1B ALT values correlated with change in histology.
- -JPGN 2006; 43: 209. Review of 91 cases; 7 c cirrhosis at presentation (mean 11.7yrs)
- -Clin Gastro & Hep 2005; 3: 910. cirrhosis in 71% after 60 years in Asian patients; 25% in Caucasian pts 61-80 who presumably had disease for shorter interval.
- -Gastroenterology 2003; 125: 1695. obesity/insulin resistance worsens fibrosis in HCV
- -Gastroenterology 2002; 123: 483-491. IFN Rx improved survival; n=2889. retrospective study.
- -JPGN 2001;33: 22A. spontaneous clearance in 30% during short f/u; n=145.
- -Hepatology 2000; 32: 91-96. Low likelihood of progression in cohort followed for 20yrs.