1. Common Medical Problems in Opioid-Addicted Patients Diana L. Sylvestre, MD Assistant Clinical Professor of Medicine University of CA, San Francisco Executive Director Organization to Achieve Solutions in Substance-Abuse (O.A.S.I.S.) Oakland, CA

2. Case Discussion R.B., 53 y.o A.A. male, 26 yr. history of IDU, regular use 2 yr. Sober for 2 weeks after a recent 21-day methadone detox but now using small amounts of heroin again. Requesting buprenorphine therapy. Only medical problem: sometimes his BP is high, but never took medications. Only medication INH: 4 mo.? Brings records. Heavy drinker for about 5-10 years in his 30’s but none for 7 years, heroin is only drug currently used.

3. Case Discussion, cont. A review of his records is notable for: Platelets 126,000 (150-450) WBC 2,400 (3,500-10,000) Alkaline Phosphatase 128 (65-110) AST 46 (20-45) ALT 67 (30-50) 6 mo ago, 39 1 yr ago

4. Case Discussion, cont. Summary: healthy 53 yo IDU on INH with mild thrombocytopenia, leukopenia, and hepatic inflammation who would like to start buprenorphine. What are the most likely diagnoses?

5. Differential Diagnosis Hepatitis C  Often asymptomatic  60-94% of IDU’s have been exposed  70-85% have chronic, active infection  10% cirrhosis after 2 decades  Mild transaminitis is common, although LFTs are often normal  Thrombocytopenia, neutropenia related to portal hypertension

6. Differential Diagnosis 2. INH: TB  Mild LFT abnormalities in 10-20%  Increased with HCV?  Alcoholism exacerbates 1. Hepatitis C

7. Differential Diagnosis 3. HIV  15-20% of long-term IDU’s are infected  The majority of HIV-infected IDU’s are coinfected with HCV  Abnormal LFT’s, leukopenia  Thrombocytopenia not uncommon 1. Hepatitis C 2. INH

8. Differential Diagnosis 4. Hepatitis B  Serologic evidence of HBV infection is found in 72-89% of IDU’s  Chronic infection develops in 5%  65% of HBV infections are subclinical  Transmission by parenteral, sexual, or perinatal routes 1. Hepatitis C 2. INH 3. HIV

9. Differential Diagnosis 5. Alcoholic Hepatitis  High rates of comorbid alcoholism in opioid-dependent patients  Liver toxicity exacerbated by HCV  AST>ALT 1. Hepatitis C 2. INH 3. HIV 4. Hepatitis B

10. The Need for Vigilance As this case indicates, the majority of long- term IDUs presenting for buprenorphine therapy will have a number of potential comorbid medical conditions that need to be addressed. What are the screening recommendations?

11. Hepatitis C Hepatitis C antibody indicates exposure, not active disease: ~25% remit spontaneously LFT’s persistently normal in 1/4 PCR testing to diagnose active disease (>$100) Genotype: best predictor of treatment response (genotype 1=40%, genotype 2,3 =80%) (>$250) Vaccinate for HBV, HAV SCREEN: HCV Ab, LFT’s, CBC

12. Hepatitis B Infection-related immunity: surface antibody and core antibody (HBSAb+ and HBcAb+) Immunization leads to HBSAb+ alone Lone HBcAb +: loss of SAb or low-level infection HBV surface antigen is positive with active infection. Confirm with HBV DNA. Treatment: high-dose IFN, lamivudine Vaccinate non-immune IDUs for HBV (3 shots) SCREEN (at least): HBSAb, HBSAg

13. HIV HIV antibody positivity confirmed with Western Blot analysis AIDS= CD4 <200 or AIDS-defining diagnosis Follow infection with CD4 and HIV viral load HAART therapy standard: 3 drugs RT’s, NNRTI’s, PI’s HCV an opportunistic infection in HIV SCREEN: HIV Ab

14. Tuberculosis More common in patients with IDU, ethnic minorities, homeless, HIV, and alcoholism Multi-drug resistance problematic PPD+: 1 cm (HIV-),.5 cm (HIV+) CXR if +, hospitalize if active pulmonary TB PPD+ treatment is 6 mo INH/B6 (12 mo HIV+), watch for hepatotoxicity Initial therapy for active TB is 4 drugs SCREEN: Annual PPD

15. Other Considerations STD’s: higher rates of syphilis, HPV, chlamydia, GC Bacterial infections: soft tissue, endocarditis COPD: cigarettes, pneumonia Hepatitis A: offer vax if HCV+ SCREEN: annual RPR, physical exam, refer for preventive health care

16. Case Discussion, cont. Based on screening recommendations, R.B. has the following testing performed: CBC, Chem panel with LFT’s HBV Surface Ab, Ag HCV Ab HIV Ab RPR No PPD needed in previous reactor

17. Results Hct and WBC wnl, platelets 137,000 (>150,000) Chem panel and LFT’s normal RPR + at 1:4, FTA negative HBV SAb and SAg negative HIV negative HCV Ab: repeatably positive

18. Case Discussion, cont. You tell R.B. that his testing indicates that he has been exposed to hepatitis C, but that he will need further testing in order to determine whether he is actively infected. You counsel him about the importance of alcohol abstinence, indicating that the low platelet count suggests liver damage. Because of your concerns about the extent of liver damage, you refer R.B. for additional evaluation prior to starting buprenorphine.

19. Results HCV RNA PCR 749,000 IU/ml Genotype 1a HAV IgG negative Abdominal ultrasound: enlarged heterogeneous liver, mild splenomegaly

20. Outcome R.B.’s regular physician is willing to consider hepatitis C treatment, but only if he is sober. On the basis of a normal albumin, bilirubin, and PT, she believes that his liver function appears adequate, and agrees that buprenorphine therapy is indicated. She vaccinates him for HAV and HBV.

21. Follow-up After a 3 month stabilization on buprenorphine, RB was referred for liver biopsy, which showed grade 3 inflammation and stage 3 fibrosis. Based on these results, R.B. is undergoing a 48- week course of pegylated interferon and ribavirin. Aside from interferon-related depression that has required treatment with an SSRI, he is tolerating the therapy nicely, and a 12-week viral load showed undetectable virus. He remains drug-free on buprenorphine.

22. Summary Chronic medical conditions, especially infectious diseases, are common in IDUs. The office-based buprenorphine practitioner may be the IDU’s only contact with the medical system

23. Summary (cont.) Therefore, all office-based buprenorphine patients need: 1. A full annual physical examination 2. Screening for: HCV HBV HIV TB Syphilis

24. Summary (cont.) *** IDU’s can be difficult patients and are complicated to manage medically. If you will be referring your patients for medical treatment, develop your physician referrals with great care, and interact liberally with them.