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Liver and Drugs<br />
Graham R Foster<br />
Professor of Hepatology<br />
Barts and The London School of<br />
Medicine
• Direct damage<br />
Liver and drugs<br />
• Indirect damage – the viruses<br />
• Opiates in cirrhosis
• Direct damage<br />
Liver and drugs<br />
• Indirect damage – the viruses<br />
• Opiates in cirrhosis
Illicit drugs that rot the liver<br />
• All drugs can cause liver damage<br />
• Some do it often, some do it rarely<br />
• The illegal drugs are no worse
Ecstasy and Liver Failure<br />
Rare but...<br />
• Ecstasy the second most common cause of<br />
liver injury in patients under the age of 25<br />
years (20%)<br />
• Patients had severe liver disease of acute<br />
onset, with jaundice, high peak of serum<br />
transaminases activity, hypoglycemia and low<br />
prothrombin activity, but no hepatic<br />
encephalopathy.<br />
• Hyperpyrexia is common<br />
J Hepatol 1998;29:394-397
Other drugs<br />
• Antidepressants (unusual with the new<br />
drugs)<br />
• Antibiotics (cholestasis with Augmentin)
• Direct damage<br />
Liver and drugs<br />
• Indirect damage – the viruses<br />
• Opiates in cirrhosis
• HBV<br />
• HCV<br />
The viruses in injectors
HBV<br />
• Acute HBV - unforgivable
Acute HBV When to worry….<br />
Abnormal INR<br />
Get on the phone
Acute HBV<br />
• 42 year old man went to Thailand<br />
• Drank a lot
Acute HBV<br />
• 42 year old man went to Thailand<br />
• Drank a lot<br />
• Came home unwell<br />
• Admitted to local hospital with ALT 1200
Acute HBV<br />
• 42 year old man went to Thailand<br />
• Drank a lot<br />
• Came home unwell<br />
• Admitted to local hospital with ALT 1200<br />
• Diagnosis – alcohol abuse
Acute HBV<br />
• 42 year old man went to Thailand<br />
• Drank a lot<br />
• Came home unwell<br />
• Admitted to local hospital with ALT 1200<br />
• Diagnosis – alcohol abuse<br />
• Bed bound, difficulty moving
Acute HBV<br />
• 42 year old man went to Thailand<br />
• Drank a lot<br />
• Came home unwell<br />
• Admitted to local hospital with ALT 1200<br />
• Diagnosis – alcohol abuse<br />
• Bed bound, difficulty moving<br />
• Referred to RLH with increasing creatinine
Acute HBV<br />
BEWARE –<br />
VACCINATE, VACCINATE, VACCINATE
ALT<br />
0<br />
Immunotolerant<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
HBV – The Disease<br />
Immunoactive<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
Immnunosurveillance<br />
Phase<br />
HBeAg -<br />
HBsAg +<br />
Immunoescape<br />
phase<br />
HBeAg -<br />
HBsAg +<br />
30<br />
Time (Years)<br />
Upper limit<br />
of normal
ALT<br />
0<br />
Immunotolerant<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
HBV – The Disease<br />
Immunoactive<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
Immnunosurveillance<br />
Phase<br />
HBeAg -<br />
HBsAg +<br />
Immunoescape<br />
phase<br />
HBeAg -<br />
HBsAg +<br />
30<br />
Time (Years)<br />
Upper limit<br />
of normal
ALT<br />
0<br />
Immunotolerant<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
HBV – The Disease<br />
Immunoactive<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
Immnunosurveillance<br />
Phase<br />
HBeAg -<br />
HBsAg +<br />
Immunoescape<br />
phase<br />
HBeAg -<br />
HBsAg +<br />
30<br />
Time (Years)<br />
Upper limit<br />
of normal
ALT<br />
0<br />
Immunotolerant<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
HBV – The Disease<br />
Immunoactive<br />
Phase<br />
HBsAg +<br />
HBeAg +<br />
Immnunosurveillance<br />
Phase<br />
HBeAg -<br />
HBsAg +<br />
Immunoescape<br />
phase<br />
HBeAg -<br />
HBsAg +<br />
30<br />
Time (Years)<br />
Upper limit<br />
of normal
Chronic HBV<br />
This virus kills people<br />
This virus lasts for many years<br />
This virus is easy to transmit
• HBV<br />
• HCV<br />
The viruses in injectors
Hepatitis C: The Basics<br />
• Blood borne virus<br />
• Common in injecting drug users<br />
• Causes very slowly progressive liver<br />
disease (30% have cirrhosis after 30<br />
years)
Hepatitis C – what does it do ?
SVR (%)<br />
Treating HCV overall<br />
Genotype non 1 – 40 KD PEG IFNα2a + Ribavirin<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
78% 78%<br />
73%<br />
24 weeks 48 weeks<br />
77%<br />
n=106 n=162 n=111 n=165<br />
PEG IFN<br />
RBV 800<br />
PEG IFN<br />
RBV 1000/1200<br />
Hadziyannis et al Ann Intern Med 2004:140;346-355<br />
PEG IFN<br />
RBV 800<br />
PEG IFN<br />
RBV 1000/1200
SVR (%)<br />
Treating HCV overall<br />
Genotype 1 – 40 KD PEG IFNα2a + Ribavirin<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
29%<br />
41% 40%<br />
24 weeks 48 weeks<br />
51%<br />
n=101 n=118 n=250 n=271<br />
PEG IFN<br />
RBV 800<br />
PEG IFN<br />
RBV 1000/1200<br />
Hadziyannis et al Ann Intern Med 2004:140;346-355<br />
PEG IFN<br />
RBV 800<br />
PEG IFN<br />
RBV 1000/1200
Treating Injectors - Response<br />
Compliant with<br />
therapy<br />
N=47<br />
(48 treatment<br />
episodes)<br />
Completed follow up<br />
N=36<br />
(37 treatment episodes)<br />
SVR<br />
n = 21 (57%)<br />
(7 geno 1,<br />
14 non-1)<br />
Completed therapy<br />
N= 58<br />
(60 treatment episodes)<br />
No SVR<br />
n = 16 (43%)<br />
(9 genot 1,<br />
7 non-1)<br />
SVR<br />
n = 4 (33%)<br />
(3 geno 1,<br />
1 non-1)<br />
Non-compliant<br />
N=11<br />
(12 treatment<br />
episodes)<br />
Completed follow up<br />
N=11<br />
12 treatment episodes)<br />
No SVR<br />
n = 8 (67%)<br />
(3 geno 1,<br />
5 non-1)<br />
50
Treating Injectors - Response<br />
Compliant with<br />
therapy<br />
N=47<br />
(48 treatment<br />
episodes)<br />
Completed follow up<br />
N=36<br />
(37 treatment episodes)<br />
SVR<br />
n = 21 (57%)<br />
(7 geno 1,<br />
14 non-1)<br />
Completed therapy<br />
N= 58<br />
(60 treatment episodes)<br />
No SVR<br />
n = 16 (43%)<br />
(9 genot 1,<br />
7 non-1)<br />
SVR<br />
n = 4 (33%)<br />
(3 geno 1,<br />
1 non-1)<br />
Non-compliant<br />
N=11<br />
(12 treatment<br />
episodes)<br />
Completed follow up<br />
N=11<br />
12 treatment episodes)<br />
No SVR<br />
n = 8 (67%)<br />
(3 geno 1,<br />
5 non-1)<br />
51
Treating Injectors - Response<br />
Compliant with<br />
therapy<br />
N=47<br />
(48 treatment<br />
episodes)<br />
Completed follow up<br />
N=36<br />
(37 treatment episodes)<br />
SVR<br />
n = 21 (57%)<br />
(7 geno 1,<br />
14 non-1)<br />
Completed therapy<br />
N= 58<br />
(60 treatment episodes)<br />
No SVR<br />
n = 16 (43%)<br />
(9 genot 1,<br />
7 non-1)<br />
SVR<br />
n = 4 (33%)<br />
(3 geno 1,<br />
1 non-1)<br />
Non-compliant<br />
N=11<br />
(12 treatment<br />
episodes)<br />
Completed follow up<br />
N=11<br />
12 treatment episodes)<br />
No SVR<br />
n = 8 (67%)<br />
(3 geno 1,<br />
5 non-1)<br />
52
Treating Injectors - Response<br />
Compliant with<br />
therapy<br />
N=47<br />
(48 treatment<br />
episodes)<br />
Completed follow up<br />
N=36<br />
(37 treatment episodes)<br />
SVR<br />
n = 21 (57%)<br />
(7 geno 1,<br />
14 non-1)<br />
Completed therapy<br />
N= 58<br />
(60 treatment episodes)<br />
No SVR<br />
n = 16 (43%)<br />
(9 genot 1,<br />
7 non-1)<br />
SVR<br />
n = 4 (33%)<br />
(3 geno 1,<br />
1 non-1)<br />
Non-compliant<br />
N=11<br />
(12 treatment<br />
episodes)<br />
Completed follow up<br />
N=11<br />
12 treatment episodes)<br />
No SVR<br />
n = 8 (67%)<br />
(3 geno 1,<br />
5 non-1)<br />
53
Treating Injectors - Response<br />
Compliant with<br />
therapy<br />
N=47<br />
(48 treatment<br />
episodes)<br />
Completed follow up<br />
N=36<br />
(37 treatment episodes)<br />
SVR<br />
n = 21 (57%)<br />
(7 geno 1,<br />
14 non-1)<br />
Completed therapy<br />
N= 58<br />
(60 treatment episodes)<br />
No SVR<br />
n = 16 (43%)<br />
(9 genot 1,<br />
7 non-1)<br />
SVR<br />
n = 4 (33%)<br />
(3 geno 1,<br />
1 non-1)<br />
Non-compliant<br />
N=11<br />
(12 treatment<br />
episodes)<br />
Completed follow up<br />
N=11<br />
12 treatment episodes)<br />
No SVR<br />
n = 8 (67%)<br />
(3 geno 1,<br />
5 non-1)<br />
54
• Common<br />
• Treatable<br />
HCV in Drug Users
• Direct damage<br />
Liver and drugs<br />
• Indirect damage – the viruses<br />
• Opiates in cirrhosis
YES<br />
Should we reduce opiates in<br />
cirrhosis?<br />
• We know they exacerbate encephalopathy<br />
• We know they are metabolised poorly
YES<br />
Should we reduce opiates in<br />
cirrhosis?<br />
• We know they exacerbate encephalopathy<br />
• We know they are metabolised poorly<br />
NO<br />
• Patients withdraw and take street gear,<br />
which is worse
Should we reduce opiates in<br />
• Talk to the patient<br />
cirrhosis?<br />
What I do<br />
• Reduce slowly – with the patients approval<br />
• Maintain a low dose of methadone
Liver and Drugs<br />
Summary<br />
• Direct drug damage is rate<br />
• Viral hepatitis is the big issue<br />
• Stop HBV with a vaccine, treat HCV<br />
• Modify opiate intake
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