1. Patient Information - Viral Hepatitis B (HBV)
Liver consequences and management
Patient information - HBV

2. What is Hepatitis B (HBV)?
In this Presentation
What is Hepatitis B (HBV)?
Epidemiology
Impact on the liver?
Liver Diagnosis: non invasive options
Patient information - HBV

3. Patient information - HBV
What is Hepatitis B?
Patient information - HBV

4. How is the virus transmitted?
Hepatitis B is the most common serious liver infection. It is caused by the Hepatitis B virus that attacks the liver
Hepatitis B virus is spread through contact with the blood or other body fluids of an infected person.
A person can become infected by:
contact with a mother’s blood and body fluids at the time of birth;
contact with blood and body fluids through
breaks in the skin such as bites, cuts, or sores;
contact with objects that could have blood or body fluids on them such as toothbrushes or razors;
having unprotected sex with an infected person;
sharing needles when injecting drugs;
being stuck with a used needle on the job.
Patient information - HBV

5. Patient information - HBV
Symptoms
Hepatitis B: “the silent infection”
Most people do not have symptoms
Most common manifestation are flu like symptoms
Only 1% have severe symptoms while their body attacks the virus
Flu like symptoms
Severe symptoms (Life threatening condition, requires medical attention)
Fever
Vomiting and mild nausea
Muscle or joint pain
Loss of appetite
Nausea and vomiting
Yellow eyes and skin (jaundice)
Bloated or swollen stomach
Patient information - HBV

6. Acute or Chronic? Acute (short-term) illness (90% of hep B cases) VS
Chronic (long-term) infection. (10% of hep B cases)
Clearance within 6 month
Virus remaining in blood for more than 6 month
This can lead to:
loss of appetite
diarrhea and vomiting
tiredness
jaundice (yellow skin or eyes)
pain in muscles, joints, and stomach
Can be very serious, and often leads to:
liver damage (cirrhosis)
liver cancer
death
More common in adults.
More common among infants and children.
Children usually do not have acute illness.
Infected people can spread HBV to others, even if they don’t appear sick.
Patient information - HBV

7. Epidemiology Who is infected?
Patient information - HBV

8. Hepatitis B - Epidemiology
To Remember
Over 300 millions infection cases worldwide
Hepatitis B remains to often undiagnosed : about 80%
About 1 out of 5 patients is treated after diagnosis
About 50% of treated patient don’t respond to treatment and continue to develop liver injury
Patient information - HBV

9. Hepatitis B - Epidemiology
To Remember
In 2005, about 51,000 people became infected with hepatitis B.
About 1.25 million people in the United States have chronic HBV infection.
Each year about 3,000 to 5,000 people die from cirrhosis or liver cancer caused by HBV.
Asia ( China) : 10% HBV , most of them not diagnosed
Patient information - HBV

10. Patient information - HBV
Hep B vaccine?
About vaccines
Prevents hepatitis B disease and its serious consequences like hepatocellular carcinoma (liver cancer). Therefore, this is the first anti-cancer vaccine.
Medical, scientific and public health communities strongly endorse using hepatitis B vaccine as a safe and effective way to prevent disease and death.
Scientific data show that hepatitis B vaccines are very safe for infants, children, and adults.
Persons allergic to yeast should not be vaccinated with vaccines containing yeast.
Patient information - HBV

11. Patient information - HBV
Impact on the liver?
Patient information - HBV

12. The Liver disease progression
Virus
Hep B
Liver
Inflammation
presence of inflammatory cells in the liver
change in liver structure
slowed blood circulation
Fibrosis
scarring of the liver due to excessive liver damage
most apparent clinical feature: hypertension
Cirrhosis
liver becomes permanently scarred
alteration of liver structure
liver function is impaired
NAFLD - What can we do?
Having acknowledged the limitations of our current knowledge about NAFLD therapy, certain pharmacotherapies do appear promising based on preliminary results. Insulin sensitizing agents are generally the most consistently helpful treatment. Trials of 3 different TZDs (troglitazone, rosaglitazone, pioglitazone) demonstrate improved aminotransferases and liver histology. Metformin’s effects on histology have been assessed less often, but 3 clinical trials demonstrate improved aminotransferases and one showed decreased liver fat on ultrasonography. Other agents have been tested in many fewer subjects but show some benefits on aminotransferases and/or liver histology. Surprisingly, although early, small studies of ursodeoxycholic acid suggested that this drug might be beneficial in NAFLD, a recent, larger randomized and placebo-controlled trial was unable to demonstrate a positive effect on liver histology. Life-style modification to reduce obesity and improve insulin sensitivity is a logical approach to the treatment of NAFLD because this strategy clearly benefits other components of the metabolic syndrome.
However, the utility of weight reduction in improving NAFLD remains uncertain. At this point, the optimal dietary composition (e.g., high or low fat/carbohydrate or protein, type of dietary fat) to lessen liver damage is unknown.
Concern about severe caloric restriction lingers because there is old evidence that hepatic decompensation accompanied rapid, extreme weight loss following jejunal-ileal bypass surgery for morbid obesity.
Because NAFLD is often obscure in the morbidly obese, many patients with unsuspected NAFLD have undergone more modern weight reducing surgeries, including gastric restriction with or without gastric bypass. Follow-up studies of patients who had NAFLD demonstrated on intra-operative liver biopsies are emerging. Results are conflicting. In general, gastric bypass seems to reduce hepatic steatosis but its effects on steatohepatitis and cirrhosis are less consistent. While the approach appears to be safer than jejeunal-ileal bypass surgery for morbid obesity, cases of post-op hepatic decompensation have been reported. Whether or not any of these outcomes are influenced by the type of surgery (restriction versus bypass) is also unknown.
Angulo P. Current best treatment for non-alcoholic fatty liver disease. Expert Opin Pharmacother 2003;4:
Medina J, Fernandez-Salazar LI, Garcia-Buey L, Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care 2004;27:
Caldwell SH, Hespenheide EE, Redick JA, al e. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastro 2001;96:
Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 2003;38:
Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004;39:
Marchesini G, Brizl M, Bianchi G, Tomasselli S, Zoll M, Melchlonda N. Metformin in non-alcoholic steatohepatitis. Lancet 2001;358:
Duseja A, Murlidharan R, Bhansali A, Sharma S, Das A, Das R, Chawla Y. Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis--a preliminary report. Indian J Gastroenterol 2004;23:12-15.
Nair S, Diehl AM, Wiseman M, Farr GH, Jr., Perrillo RP. Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 2004;20:23-28.
Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, Lymp JF, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004;39:
Chamberlain J, DeMouy J. Diet and exercise dramatically delay type 2 diabetes; diabetes medication, metformin, also effective. U.S. Department of Health and Human Services Press Release ;Sect.
Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. Jama 2003;289:
Scheen AJ. Management of the metabolic syndrome. Minerva Endocrinol 2004;29:31-45.
Lavine JE. Vitamin E treatment of non-alcoholic steatohepatitis in children: a pilot study. J Pediatr 2000;136:
Roberts EA. Nonalcoholic steatohepatitis in children. Curr Gastroenterol Rep 2003;5:
Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003;98:
Harrison SA, Ramrakhiani S, Brunt EM, Anbari MA, Cortese C, Bacon BR. Orlistat in the treatment of NASH: a case series. Am J Gastroenterol 2003;98:
Daubioul CA, Horsmans Y, Lambert P, Danse E, Delzenne NM. Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Eur J Clin Nutr 2005.
Vyberg M, Ravn V, Andersen B. Patterns of progression of liver injury following jejunoileal bypass for morbid obesity. Liver 1987;7:
Deitel M, Shahi B, Anand PK, Deitel FH, Cardinell DL. Long-term outcome in a series of jejunoileal bypass patients. Obes Surg 1993;3:
Dhabuwala A, Cannan RJ, Stubbs RS. Improvement in co-morbidities following weight loss from gastric bypass surgery. Obes Surg 2000;10:
Gholam PM, Kotler DP, Flancbaum LJ. Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg 2002;12:49-51.
Blackburn GL, Mun EC. Effects of weight loss surgeries on liver disease. Semin Liver Dis 2004;24:
Hepatic insufficiency/ Liver failure
Hepatocellular carcinoma (Liver cancer)
Hemorrhage
Patient information - HBV 12

13. The Liver disease progression
Virus
Hep B
Liver
Inflammation
presence of inflammatory cells in the liver
change in liver structure
slowed blood circulation
Fibrosis
scarring of the liver due to excessive liver damage
most apparent clinical feature: hypertension
Cirrhosis
liver becomes permanently scarred
alteration of liver structure
liver function is impaired
How to measure liver disease progression?
NAFLD - What can we do?
Having acknowledged the limitations of our current knowledge about NAFLD therapy, certain pharmacotherapies do appear promising based on preliminary results. Insulin sensitizing agents are generally the most consistently helpful treatment. Trials of 3 different TZDs (troglitazone, rosaglitazone, pioglitazone) demonstrate improved aminotransferases and liver histology. Metformin’s effects on histology have been assessed less often, but 3 clinical trials demonstrate improved aminotransferases and one showed decreased liver fat on ultrasonography. Other agents have been tested in many fewer subjects but show some benefits on aminotransferases and/or liver histology. Surprisingly, although early, small studies of ursodeoxycholic acid suggested that this drug might be beneficial in NAFLD, a recent, larger randomized and placebo-controlled trial was unable to demonstrate a positive effect on liver histology. Life-style modification to reduce obesity and improve insulin sensitivity is a logical approach to the treatment of NAFLD because this strategy clearly benefits other components of the metabolic syndrome.
However, the utility of weight reduction in improving NAFLD remains uncertain. At this point, the optimal dietary composition (e.g., high or low fat/carbohydrate or protein, type of dietary fat) to lessen liver damage is unknown.
Concern about severe caloric restriction lingers because there is old evidence that hepatic decompensation accompanied rapid, extreme weight loss following jejunal-ileal bypass surgery for morbid obesity.
Because NAFLD is often obscure in the morbidly obese, many patients with unsuspected NAFLD have undergone more modern weight reducing surgeries, including gastric restriction with or without gastric bypass. Follow-up studies of patients who had NAFLD demonstrated on intra-operative liver biopsies are emerging. Results are conflicting. In general, gastric bypass seems to reduce hepatic steatosis but its effects on steatohepatitis and cirrhosis are less consistent. While the approach appears to be safer than jejeunal-ileal bypass surgery for morbid obesity, cases of post-op hepatic decompensation have been reported. Whether or not any of these outcomes are influenced by the type of surgery (restriction versus bypass) is also unknown.
Angulo P. Current best treatment for non-alcoholic fatty liver disease. Expert Opin Pharmacother 2003;4:
Medina J, Fernandez-Salazar LI, Garcia-Buey L, Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care 2004;27:
Caldwell SH, Hespenheide EE, Redick JA, al e. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastro 2001;96:
Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 2003;38:
Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004;39:
Marchesini G, Brizl M, Bianchi G, Tomasselli S, Zoll M, Melchlonda N. Metformin in non-alcoholic steatohepatitis. Lancet 2001;358:
Duseja A, Murlidharan R, Bhansali A, Sharma S, Das A, Das R, Chawla Y. Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis--a preliminary report. Indian J Gastroenterol 2004;23:12-15.
Nair S, Diehl AM, Wiseman M, Farr GH, Jr., Perrillo RP. Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 2004;20:23-28.
Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, Lymp JF, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004;39:
Chamberlain J, DeMouy J. Diet and exercise dramatically delay type 2 diabetes; diabetes medication, metformin, also effective. U.S. Department of Health and Human Services Press Release ;Sect.
Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. Jama 2003;289:
Scheen AJ. Management of the metabolic syndrome. Minerva Endocrinol 2004;29:31-45.
Lavine JE. Vitamin E treatment of non-alcoholic steatohepatitis in children: a pilot study. J Pediatr 2000;136:
Roberts EA. Nonalcoholic steatohepatitis in children. Curr Gastroenterol Rep 2003;5:
Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003;98:
Harrison SA, Ramrakhiani S, Brunt EM, Anbari MA, Cortese C, Bacon BR. Orlistat in the treatment of NASH: a case series. Am J Gastroenterol 2003;98:
Daubioul CA, Horsmans Y, Lambert P, Danse E, Delzenne NM. Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Eur J Clin Nutr 2005.
Vyberg M, Ravn V, Andersen B. Patterns of progression of liver injury following jejunoileal bypass for morbid obesity. Liver 1987;7:
Deitel M, Shahi B, Anand PK, Deitel FH, Cardinell DL. Long-term outcome in a series of jejunoileal bypass patients. Obes Surg 1993;3:
Dhabuwala A, Cannan RJ, Stubbs RS. Improvement in co-morbidities following weight loss from gastric bypass surgery. Obes Surg 2000;10:
Gholam PM, Kotler DP, Flancbaum LJ. Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg 2002;12:49-51.
Blackburn GL, Mun EC. Effects of weight loss surgeries on liver disease. Semin Liver Dis 2004;24:
Hepatic insufficiency/ Liver failure
Hepatocellular carcinoma (Liver cancer)
Hemorrhage
Patient information - HBV 13

14. Non-Invasive liver diagnosis and staging
Patient information - HBV

15. Traditional method: the liver biopsy
Pro
Specific
Sensitive
Good diagnostic and prognostic information
Con
Invasive and painful (30% of cases)
Expensive
Associated morbidity (ex: haemorrhage: 3/1.000)
Associated mortality (3/10.000)
Not 100% reliable
variability due to sample quality
as analyses only 1/ of total liver tissue
Patient information - HBV
Siegel 2005; Ratziu 2005; Bateller 2005; Bravo 2001

16. The liver biopsy analyses only 1/50.000° of total liver tissue….
Minimal fibrosis F2
Moderate fibrosis F4
Cirrhosis
Patient information - HBV

17. Patient information - HBV
… clearly not enough!
The very same liver!!
Patient information - HBV
Bedossa et al, Hepatology 2003

18. The non invasive option: liver Biomarkers
New concept in liver diseases
Use of biomarkers validated for the most frequent chronic liver diseases
Public health interest :
SCREENING advanced fibrosis
Treatment efficacious , at least for HCV and HBV
USA: “FibroSure”
A new Solution to unmet clinical needs: FibroTest
Simple, least expensive
Accurate
Good diagnostic value
for every stage of fibrosis
Dynamic assessment: after successful/ failed therapy
Good prognostic value (as good as biopsy)
Universal fibrosis marker: validated in all common liver diseases (83 publications, 33 validations)
A Validated screening tool of at risk patients
Accepted use in clinical trials
Patient information - HBV

19. FibroTest in Hepatitis B
Virus
Hep B
Liver
Inflammation
presence of inflammatory cells in the liver
change in liver structure
slowed blood circulation
Fibrosis
scarring of the liver due to excessive liver damage
most apparent clinical feature: hypertension
Cirrhosis
liver becomes permanently scarred
alteration of liver structure
liver function is impaired
ActiTest/ ActiSure (usa)
(Part of FibroTest/FirboSure) Viral inflammation quantification
FibroTest/ FibroSure (usa)
Liver fibrosis measurement
Patient information - HBV

20. Simple. Reliable. Cost-effective.
How to? In 4 easy steps!
Simple. Reliable. Cost-effective.
Notes
Step 1: Patient goes to a prescribing doctor.
Step 2: With the prescription, goes to a validated lab (list on )
Step 3: Calculation algorithms and security controls are automatically performed
Step 4: Test results delivered within 24 hours
Patient information - HBV