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Table of Content - Volume 6 Issue 2 - May 2017


 

Acute fulminant Hepatitis B treated with entecavir

 

Jayvirsinh Atodariya1, Virendra C Patil2*, Tejas Rane3, Sandeep Patil4

 

{1Department of Medicine} {2Department of Gastroenterology} Krishna Institute of Medical Sciences (KIMS) Deemed university, Karad, Maharashtra, INDIA.

Email: drtejasrane@gmail.com

 

Abstract              Hepatitis B virus (HBV) infection constitutes a serious global health problem. Acute and subacute liver failure is common complications of viral hepatitis in India and HBV is reckoned to be the etiological agent in 42% and 45% of adult cases, respectively. Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. We present here a case of 25 year old lady affected by severe acute hepatitis B with progressive worsening of clinical Condition. The patient was treated with Entecavir. We observed rapid clinical and laboratory improvements. Entecavir should be carefully considered for the treatment of severe acute hepatitis B cases.

Key Words: Hepatitis B.

 

INTRODUCTION

The most widely accepted definition of ALF includes evidence of coagulation abnormality, usually an International Normalized Ratio (INR) 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of less than 26 weeks duration1. Patients with Wilson disease, vertically-acquired hepatitis B virus (HBV), or autoimmune hepatitis may be included in spite of the possibility of cirrhosis if their disease has only been recognized for less than 26 weeks. A number of other terms have been used for this condition, including fulminant hepatic failure and fulminant hepatitis or necrosis. ‘‘Acute liver failure’’ is a better overall term that should encompass all durations up to 26 weeks. Acute hepatitis B viral (HBV) infection can sometimes take a severe course, leading to liver failure due to hepatic necrosis with a death rate of 80%.2-3 Emergency liver transplantation is often the only therapeutic option available.4 There are many drugs approved for the treatment of chronic hepatitis B, that inhibit the replication of the HBV with a low toxicity and a good resistance profile such lamivudine, adefovir, tenofovir, entecavir and telbivudine. 2017 EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure suggest early treatment with antiviral therapy decreases the risk of progression to ALF5. Of note, the nucleoside analog lamivudine (and possibly other nucleos(t)ide analogues), used widely in the treatment of chronic hepatitis B, may be considered in patients with acute hepatitis B, although evidence of efficacy is equivocal6-7. The new guidelines endorsed by America Association for the study of liver diseases (AASLD) recommend- nucleos(t)ide analogues should be considered for hepatitis B-associated acute liver failure and for prevention of post-transplant recurrence.(III)

 

CASE REPORT

My patient 25 year old Indian Housewife residing at morgiri patan satara brought by relative in casualty at 10.30 pm with C/O Altered behaviour since evening

  • Patient was apparently alright one day prior to admission. Patient slept quietly for whole day. In the evening her behaviour was altered-confused and then she became rowdy. So patient was taken to local doctor from there was referred to our hospital for further management. Her history was negative for any major illness, drug abuse, alcohol, neuro-deficit, involuntary movement, chest pain, dyspnea, trauma. Her sleep pattern was altered with daytime sleepiness and having loss of appetite since few days. Patient was lactating mother with 6 months FTND with no complication. At hospital admission patient was drowsy with glass glow coma scale of 10. Examination showed a frank jaundice and ascites. The laboratory examinations showed bilirubin (t)- 12.1, SGOT-1676, SGPT-2000, ALT-457, Hb-12.9, TLC-15300, Plt 2.10, Pt/INR-4.3 ABG s/o metabolic acidosis with lactic acid levels of 2.8, serum ammonia levels of 1256.6. On strip HIV, HBsAg, HCV reports were negative USG s/o moderate ascitis, mild increase echo texture of liver. MRI brain studies were normal. Patient was given supportive treatment with adqueate hydration, lactulose solution with IV FFP tranfusion. The patient showed a progressive worsening of the clinical condition with fever, jaundice increased and became stuporous with preserved corneal reflexes, GCS 5. She was electively intubated, put on mechanical ventilation. Patients HbsAg, HCV, HAV, HEV were send on ElISA, of which HbsAg came reactive. Patients Ceruloplasmin, Hepatitis Be Antigen, Hepatitis Delta IgG antibodies, Hepatitis B viralLoad were sent.
  • At this stage, the patient presented criteria of severe acute hepatitis B, thus together with general supportive therapies, we started “ off label “ treatment with entecavir 0.5mg daily. The patient relative was informed that the drug was not approved for this indication and they gave consent for treatment. The ceruloplasmin was 0.16, HepatitisBe antigen was 0.26, Hepatitis Delta IgG antibodies were negative, Hepatitis B viral load was 29250. After three days of antiviral treatment the patient was conscious and obeying simple verbal commands, icterus and ascites reduced. One week after the start of entacavir treatment, the laboratory exams confirmed the improvement of hepatic function : bilirubin(t)- 7.2, SGOT-60, SGPT-221, ALT-187, and Pt/INR- 1.8
  • The patient was extubated after one week and a month from starting entecavir, ascitic effusion disappeared, coagulation parameters were normalised and jaundice reduced marginally. Therapy is continued with entecavir 0.5mg day. We have planned continued the treatment with antiviral until 3 months after HBsAg seroconversion or 6 months after HBeAg seroconversion with reference of Harrison’s text book of internal medicine.

 

RESULTS

Table 1:

Date

Units

22/6

24/6

28/6

2/7

4/7

HB

g/dl

12.9

11.1

8.5

9.1

 

TLC

/ul

15300

6400

8600

5000

 

PLT

Lakh/cumm

2.10

1.50

90000

1.05

 

PtINR

 

4.3

2.3

 

1.8

 

BSl

Mg/dl

59

86

123

89

 

BUN

Mg/dl

21

 

13

14

 

Cr

Mg/dl

1.0

 

0.8

.8

 

Na

mEq/dl

141

134

138

132

 

K

mEq/dl

4.2

4.1

2.9

3.1

 

Ca

Mg/dl

8.0

 

10.2

 

 

Mg

Mg/dl

1.5

 

1.8

 

 

PO4

Mg/dl

2.2

 

2.7

 

 

Bil(T)

Mg/dl

12.1

10.4

7.2

 

7.7

Direct

Mg/dl

5.8

4.0

3.2

 

4.7

Indirect

Mg/dl

6.3

6.4

4.0

 

3.0

S.G.O.T

IU/L

1676

273

60

 

86

S.G.P.T

IU/L

2000

1164

221

 

99

Alkaline phosphate

U/L

457

331

187

 

112

Serum proteins

g/dl

5.9

5.9

5.8

 

5.0

Albumin

g/dl

3.7

3.2

2.7

 

2.8

Globulins

g/dl

3.2

2.7

3.1

 

2.2

 


DISCUSSION

We observed rapid improvement of a severe acute hepatitis B treated with entecavir, in accordance with previous reports4,8,9. In medical literature there are divergent data regarding the use of antiviral drugs to treat acute severe hepatitis B. For instance, lamivudine has proved no better than placebo,10 while others showed a reduction of mortality rate8-11. Theoretically lamivudine or telbivudine might be a reasonable choice but unfortunately HBV-resistance to lamivudine is increasingly reported. Monotherapy with entecavir, a new generation drug, showed encouraging preliminary results in patients affected by acute severe hepatitis B4,8,9. Furthermore clinical trials of long-term entecavir treatment of chronic hepatitis B have shown a very low rate of resistance to this drug compared with other antiviral. So in severe acute hepatitis B, this drug seems to be a good reasonable choice when resistance profile is unknown.12 Tenofovir and adefovir may not be optimal because of their potential for nephrotoxicity12 The main concerns about the use of anti-HBV drugs during the acute phase are principally linked to two factors: first, the antiviral therapy is generally not necessary because more than 95% of acute infections solve spontaneously12. Second, early antiviral therapy theoretically may inhibit the production of neutralizing antibody in the early phase of the disease and delays the appearance of anti-HBs but studies did not observe significant differences13. In the reported case, HBsAg seroconversion haven’t appeared yet and she is still on entecavir 0.5mg once daily. The duration of antiviral treatment is not established; However, this issue is still controversial: EASL guidelines recommend therapy to be continued for at least 3 months after anti-HBs appearance, while AASLD ones until HBsAg clearance is confirmed7. Further studies are necessary to support the appropriateness and the duration of entecavir treatment in cases of acute severe hepatitis B. Studies indicates that early treatment with Entecavir could induce a prompt clinical, biochemical, serological, and virological response in patients with severe acute hepatitis B, and this could significantly decrease the incidence of liver failure and mortality of these patients, and a rapid decline of HBV DNA load is a good predictor for the outcome of the treatment[5,15,16] However, too early Entecavir administration hinders seroconversion. Thus, a further prospective study with a larger number of patients is needed. Further, more clinical trials and investigation of treatment of AHB with Entecavir and other agents are needed. In conclusion Entecavir is a powerful tool with which to treat severe acute hepatitis B. It reduces dramatically viral load with the rapid clinical and biochemical recovery with negligible side effects. The drug is cost effective and can be given orally. It may modify the immune status of patients and further multicentre trials are needed to see its effect on immune status and on overall survival benefits and whether it prevents the progression to CLD. Meanwhile the possible use of this drug should be considered for selected patients with acute hepatitis B.

 

CONCLUSION

  • Entecavir is an oral nucleoside analogue which inhibits reverse transcriptase of HBV. It can be given orally and is cost effective with minimal side effects.
  • Early treatment with Entecavir induces a prompt clinical, biochemical, serological, and virological response in patients with severe acute hepatitis B and may improve survival.
  • However it may alter the immune system as it may delay the seroconversion in severe acute hepatitis B for which further trials are needed.
  • Entecavir may decrease the incidence of liver failure and mortality in severe acute hepatitis B.
  • We recommend use of Entecavir in severe acute hepatitis B.

 

REFERENCES

  1. Trey C, Davidson CS. The management of fulminant hepatic failure. In: Popper H, Schaffner F, eds. Progress in Liver Diseases. New York: Grune and Stratton, 1970:282-298
  2. Wright TL, Lau JY. Clinical aspects of hepatitis B virus infection. Lancet. 1993; 342:1340-1344. doi:10.1016/0140- 6736(93)92250-W
  3. Antoniu E, Luca V. Features of clinical evolution of severe acute viral hepatitis. Series of 72 cases. Rev Med Chir Soc Med Nat Iasi. 2010; 114: 95-100. PMid:20509283
  4. De Socio GV, Mercuri A, Di Candilo F, Baldelli F. Entecavir to treat severe acute hepatitis B. Scand J Infect Dis. 2009; 41: 703-704. doi:10.1080/00365540903062705 PMid:19544224
  5. Jochum C, Gieseler RK, Gawlista I, Fiedler A, Manka P, Saner FH, et al. Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virus replication and potentially its sequelae. Digestion 2009;80:235–240
  6. Mindikoglu AL, Regev A, Schiff ER. Hepatitis B reactivation after cytotoxic chemotherapy: the disease and its prevention. Clin Gastroenterol Hepatol 2006:4:1076-81
  7. Lok ASF, McMahon BJ. AASLD Practice Guideline, Chronic Hepatitis B: Update of Recommendation 2009; 50:661-2.
  8. Girke J, Wedemeyer H, Wiegand J, Manns MP, Tillmann HL. Acute hepatitis B: is antiviral therapy indicated? Two case reports. Dtsch Med Wochenschr. 2008; 133:1178- 1782. doi:10.1055/s-2008-1077235 PMid:18491273
  9. Jochum C, Gieseler RK, Gawlista I, Fiedler A, Manka P, Saner FH, Roggendorf M, Gerken G, Canbay A. Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virus replication and potentially its sequelae. Digestion. 2009; 80:235-40. doi:10.1159/000236009 PMid:19828954
  10. Kumar M, Satapathy S, Monga R, Das K, Hissar S, Pande C, Sharma BC, Sarin SK. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology. 2007; 45:97-101. doi:10.1002/hep.21486 PMid:17187417
  11. Yu JW, Sun LJ, Zhao YH, Kang P, Li SC. The study of efficacy of lamivudine in patients with severe acute hepatitis B. Dig Dis Sci. 2010; 55: 775-783. doi:10.1007/s10620-009-1060-5 PMid:19957031
  12. Lok A S F, McMahon BJ. Chronic Hepatitis B: Update 2009. AASLD practice guideline update. Hepatology 2009; 50: 661-662. doi:10.1002/hep.23190 PMid:19714720
  13. Kumar M, Satapathy S, Monga R, Das K, Hissar S, Pande C, Sharma BC, Sarin SK. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology. 2007; 45:97-101. doi:10.1002/hep.21486 PMid:17187417
  14. EASL Clinical Practice Guidelines: management of chronic hepatitis B. European Association For The Study Of The Liver. J Hepatol. 2009; 50:227-42. doi:10.1016/j.jhep.2008.10.001 PMid:1905458
  15. De Socio GV, Sgrelli A, Tosti A, Baldelli F: Severe acute hepatitis B treated with entecavir. Mediterr J Hematol Infect Dis 2011, 3(1):e2011010
  16. Streinu-Cercel O, Streinu-Cercel A, Preotescu LL, Streinu-Cercel A: Entecavir as specific antiviral therapy in selected cases of severe acute hepatitis B. GERMS 2012, 2(1):18-22.

 


 


 


 


 

 

 


 


 



 


 

 


 

 

 


 


 









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