Liver Shorts April 2019

CL Mack et al. JPGN 2019; 68: 495-501. This multicenter prospective open-label phase I/III trial of IVIG in biliary atresia patients status-post Kasai indicated that the infusions were tolerated.  However, though this study was not powered to detect efficacy, survival with native liver was LOWER among patients who had received IVIG (n=29): 58.6% compared to the comparison placebo group 70.5% (n=64).  Thus, despite the theoretical advantages of IVIG which targets aspects of the immune system and improvement in a murine model, in practice IVIG does not appear promising for biliary atresia.

D Kim et al. Hepatology 2019; 69: 1064-74. This study shows that despite improvements in hepatitis C mortality rates associated with newer treatments, there is an overall increase in mortality rates from cirrhosis and hepatocellular carcinoma.  This increase is driven by increasing prevalence and severity of both alcoholic liver disease and nonalchoholic fatty liver disease. The overall cirrhosis-related mortality increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3%. Similarly, the overall HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at annual increase of 2%. The editorial on page 931 (TG Cotter and MR Charlton) notes that each year there are more than 40,000 deaaths associated with chronic liver disease.

H Park et al. Hepatology 2019; 69: 1032-45. This study, using Truven Health MarketScan Cata, examined the outcomes of more than 26,000 patients with newly-diagnosed hepatitis C virus (HCV) infection.  Among the 30% who received oral direct-acting antiviral (DAA) therapy, there were improved outcomes in those with and without cirrhosis. In those with cirrhosis (n=2157), DAA was associated with a 72% and 62% lower incidences of HCC and DCC [decompensated cirrhosis] respectively. In noncirrhotic HCV patients (n=23,948), DAA was associated with a 57% and 58% lower incidence of HCC and DCC respectively.  In addition to improved health outcomes, DAA treatment resulted in decrease health care costs, especially for patients with cirrhosis.

Z Kuloglu et al. JPGN 2019; 68: 371-6.  In this multicenter Turkish study, the authors identified 810 children (median age 5.6 years) with unexplained transaminase elevation (62%),unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%) and cryptogenic fibrosis or cirrhosis (6%).  LAL-D [lysosomal acid lipase deficiency] activity was deficient in 2 siblings (0.2%); both had LDL ~155.  Overall, even in at risk groups, LAL-D is rare.

Related posts:

Joshua Tree National Park

Resolution: Eradication of Hepatitis C

Eradication of hepatitis C virus (HCV) is going to be difficult despite the huge improvements in treatment.  One obstacle that has been highlighted previously has been the increase in HCV transmission associated with the opioid epidemic.  Another basic problem is establishing a ‘cascade of care’ that makes sure that those with HCV receive appropriate treatment and followup.

In a recent study (RL Epstein et al. J Pediatr 2018; 203: 34-40, editoria by KB Schwarz, W Karnsakul 7-8) describe the deficiencies in the followup of women in an obstetric clinic serving women with substance use disorders. The authors reviewed electronic records of 879 women over a 10 year period.  Key findings:

  • 85% of women were screened for HCV.  Of the 68% who were seropositive, only 72% had HCV RNA testing and 71% were viremic.
  • There were 404 infants born to women who were HCVB seropositive.  Only 45% of these infants completed AAP-recommended perinatal HCV screening.

In the commentary, the authors point to the suboptimal rates of followup.  They note that there is a “huge gap between infected women and the linkage of their infected progency to care.” Furthermore, the AASLD has recommended that “all children with HCV infection in age groups for which direct-acting antiviral agents are approved should be treated.”

My take: this study identifies gaps in followup and treatment that need to be addressed systematically if we are to realize the goal of HCV eradication.

Related blog posts:

Screenshot (383)

Eight Week Pangenomic HCV Treatment Approved

FDA Announcement Aug 3, 2017: FDA approves Mavyret for Hepatitis C

An excerpt:

The U.S. Food and Drug Administration today approved Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both. 

Mavyret is the first treatment of eight weeks duration approved for all HCV genotypes 1-6 in adult patients without cirrhosis who have not been previously treated. Standard treatment length was previously 12 weeks or more.

Related blog posts:

Gravelly Point, Arlington, VA

Liver Briefs -April 2017

JA Flemming et al. Hepatology 2017; 65: 804-12.  This cohort study (2003-2015) of 47,591 adults wait-listed for liver transplantation, using the SRTR registry, showed that the era of direct-acting antivirals for hepatitis C was associated with a drop of 32% for HCV patients who were listed compared to the numbers listed during the interferon era.

AG Feldman et al. J Pediatr 2017; 182: 217-22. This retrospective study showed that elevated lactate levels (≥2.5 mmol/L) and elevated lactate to pyruvate ratio (≥25) were NOT predictive of mitochondrial diseases in pediatric patients who presented with acute liver failure.

AG Feldman et al. J Pediatr 2017; 182: 232-38. This retrospective cohort study showed a high rate of vaccine preventable illnesses (VPIs) following liver transplantation (n=2554), occurring in 1 of 6 liver transplant recipients. Most common infections was RSV; most common VPIs: rotavirus and influenza

Saint Chappelle, Paris

Competition and Costs in HCV Market

Following FDA approval of Zepatier (Elbasvir/Grazopresvir) (related blog post:In brief: Pediatric HCV trial, Exercise for NAFLD, and … – gutsandgrowth), it is gratifying to see reductions in the cost of HCV treatment.  Merck has priced Zepatier at $54,600 for a 12-week course which is substantially lower than Sovaldi ($84.000), Harvoni ($94.500), and Viekira Pak ($83,000).

Zepatier is indicated for genotypes 1 and 4 and can be used in patients with severe renal impairment, including dialysis. It is likely that this will pressure rival drug companies to lower their prices as well.

More information: Will Zepatier Shake Up the HCV Market? This link is to an issue of “Specialty Pharmacy Continuum” but interestingly this same story (?verbatim) was published months later by “Gastroenterology and Endoscopy New” (August 2016) without acknowledging the previous publication (by same author).

Grinnell Glacier Trail, Glacier Nat'l Park

Grinnell Glacier Trail, Glacier Nat’l Park

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)

 

Hepatitis B & C -Winter 2016

The large randomized pediatric entecavir study for Hepatitis B virus (HBV) is now in print: MM Jonas et al. Hepatology 2016; 63: 377-87.  Full link to this study on previous blog: Pediatric Entecavir Data  This study has led to FDA approval for use of entecavir in children as young as 2 years.  One interesting aspect of the study was the 2.6% drug resistance rate in the second year of the study.  This further validates current recommendations to treat children with “immune active” phases (e.g. abnormal transaminases and abnormal histology).

Briefly noted:

H Roberts et al. Hepatology 2016; 63: 388-97.  This study provides prevalence data for chronic HBV, 1988-2012.  During 2011-12, there were approximately 850,000 Americans with chronic HBV infections.  Migration of persons from HBV endemic countries has “largely contributed to prevalence rates remaining constant since 1999.”

JM Wilder et alHepatology 2016; 63: 437-44. This study showed that ledipasvir/sofosbuvir was similarly effective in black and non-black patients, with SVR12 rates of 95% and 97% respectively.  This is important because older interferon-based treatments were much less effective in black patients.

TB Dick et al. Hepatology 2016; 63: 634-43.  This review provides in-depth guidance regarding drug-drug interactions relevant to the new direct-acting antiviral agents used to treat Hepatitis C viral infection.

NY City Data for HIV, HBV, HCV

NY City Data for HIV, HBV, HCV