Tag Archives: hcv

HCV now more deadly than HIV

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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).

Additional references:

  • -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.

Drink Up!

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Green tea and coffee have a lot of advocates and a number of articles suggest that each can have beneficial effects for the liver.  This month’s Hepatology describes how a green tea component, epigallocatechin-3-gallate (EGCG), inhibits hepatitis C viral (HCV) entry. ECGC acts by blocking viral attachment to target cells with all HCV genotypes; it does not affect viral replication.  Other components of green tea do not have this effect.  A complete description of green tea components is described in the discussion of the article, Hepatology 2012: 54: 1947-55.  Also, there have been preliminary dosing studies in healthy volunteers which have shown that EGCG is safe at doses of 800mg daily for four weeks.  This would be the equivalent of drinking 8-16 cups of green tea per day (Clin Cancer Res 2003; 9: 3312-19).  In order to eliminate HCV, however, even higher amounts of EGCG would be likely.

 

Coffee also has been studied and has been associated with decreasing liver fibrosis.  In addition, coffee may enhance response to HCV treatments.  To my knowledge, there have not been extensive studies of either coffee or green tea for pediatric patients.

Additional References:

  • -Gastroenterology 2011; 140: 1961. Coffee (3 cups/day) increases response to PEG/RBV in HCV
  • -Hepatology 2009; 51: 201. Coffee decreases fibrosis. n=177.
  • -Hepatology 2009; 50: 1360. Coffee intake associated with slower progression of HCV liver disease
  • -Hepatology 2009; 50: 970. Coffee -2 cups per day decreases risk of liver fibrosis & HCC. Coffee has methylxanthin which inhibits connective tissue growth factor.

The cost of progress in treating Hepatitis C

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Background information on Hepatitis C (HCV):

  • —170 million people worldwide infected with HCV, 2.7 milllion people in U.S. infected
  • —27% of worldwide cases of cirrhosis are due to HCV
  • —25% of cases of hepatocellular carcinoma are due to HCV
  • —Established treatment with pegylated interferon (PEG IFN) and ribavirin have ~40% response rates in genotype 1 (74% of HCV in U.S.) and relapses are not uncommon among responders

New treatments for Hepatitis C (in combination with previous treatments):

  • —Two new drugs: Boceprevir (BOC) & Telaprevir (TVR)
  • —Overall sustained viral response (SVR) with BOC combination 63-66% vs 73-79% with TVR combination treatment
  • —Both trials demonstrate marked improvement over previous
  • Mechanism of action: —Protease inhibitor binding to NS3 HCV target
  • —BOC: Wholesale cost $1100/week (20-44 weeks)
  • —TVR: 12weeks cost: $49,000
Previous treatments for hepatitis C typically cost about $5000 per month (http://www.familydrugguide.com/family/ub/view/Consumer_Reports_Health/526033/4/hepatitis_c_drugs).  The addition of these newer drugs could add another $50,000 to the cost of treatment.  In some cases which respond well to the newer treatments, shorter treatment periods will lower the increase in cost.  Although these drugs are expensive, they may be lifesaving and may obviate the need for liver transplantation.  Due to the potential complications of HCV, more medications are in the pipeline.  They may be easier to take but are likely to be expensive as well.  The safety & effectiveness of these medications have not been demonstrated in published pediatric studies.
Article References:
  • Hepatology 2011; 54: 1433.  Updated AASLD HCV treatment guidelines
  • NEJM 2011; 364: 1195-206, Editorial pg. 1272. Addition of boceprevir, in 1097 previously untreated pts increased SVR. In whites, 40%–>67% & in blacks from 23% –>42%. Medication given after lead-in of 4 weeks. More frequent anemia in boceprevir-treated patients (SPRINT-2 study).Boceprevir dosing: 800mg (4 capsules) TID with food. (trying to space out doses evenly).
  • NEJM 2011; 365: 1014. n=540. Telaprevir study: extended SVR 72%. In pts with rapid viral response (RVR) at 4 & 12 weeks (no detectable HCV), Telaprevir12weeksPegRbv24 was as effective as Telprevir12weeksPegRbv48. Dosing for study: Teleprevir 750mg TID, PEGalfa-2a 180mcg/wk, RBV1-1.2gm per day.  Rash in 37% (severe in 5%), anemia in 39% (severe in 6%).
  • NEJM 2011; 364: 2405, 2417, 2429 (review). Telaprevir addition:  up to 75% response in HCV genotype 1 pts. n=1095 in 1st study, n=833 in 2nd study (re-treatment study)
  • Gastroenterology 2011; 140: 746. Summary of results of boceprevir (used with IFN -alfa 2b 1.5/kg) & telaprevir (used with IFN -alfa 2a 180mcg). “Similar effectiveness” thus far. Telaprevir used for 12 weeks without lead-in period.  TVR: most frequent problem -rash & then anemia.  In practice, dosing in adults: Telaprevir will be used at 750mg TID in combination with IFN-2a 180mcg & RBV 1-1.2g/d. & used for 1st 12 weeks of Rx. This will allow ~50% of patients to have shorter Rx duration:  if HCV RNA RVR –>24week total vs 48week total in those w/o RVR.  Both drugs best for genotype 1.