Michelle B. Moreno, M.D.

1. To present a case of a young patient with hypertension

2. To discuss hepatitis C, its prevalence, diagnosis, evaluation, prevention and extrahepatic manifestations

3. To present the treatment option for this case

G.P. 29 year old male Filipino Elevated blood pressure

4 months PTA Hypertension Imidapril + HCTZ 10/12.5

ODwith good compliance

BP persistently elevated (150/80 – 180/90)

Admission

No headache, blurring of visionNo skin lesionsNo chest pain, palpitations, difficulty of

breathing, easy fatigabilityNo cough, colds, fever, night sweatsNo abdominal pain, dysuria(+) grade 2 bipedal edema 3 weeks ago

No Diabetes MellitusNo Asthma(+) Allergy to IbuprofenNo previous surgery or hospitalizationNo history of blood transfusion

(+) Hypertension – motherNo Diabetes MellitusNo AsthmaNo hepatitis

Smoker 7 pack yearsAt present, consumes 8-10 sticks per day

Occasional alcoholic drinker1 sexual partner(+) tattoo on left leg and arm x 1 yearNo illicit drug use

Conscious, coherent, not in respiratory distress

BP 160/110 HR 86 RR 17 T 36.9Good skin turgor, no skin lesions, Anicteric sclerae, pink palpebral

conjunctivae, no lymphadenopathy, no masses, no neck vein distention, JVP 8, no carotid bruit

Symmetrical chest expansion, no intercostal retractions, clear breath sounds

Adynamic precordium, PMI at 5th ICS LMCL, no heaves, no thrills, normal rate, regular rhythm, distinct S1 and S2, no murmurs, no S3, no S4

Flat, normoactive bowel sounds, no bruit, soft, no tenderness, no organomegaly, no masses,

Pulses full and equal, no edema, (+) tattoo on left leg and arm

29,M uncontrolled blood pressure Known Hypertensive BP 160/110 HR 86 (+) grade 2 bipedal edema 3 weeks ago

Hypertension stage IIR/O Secondary causes

Secondary Hypertension Renal artery stenosis Primary renal disease Pheochromocytoma Primary Aldosteronism Coarctation of aorta Hypothyroidism Primary Hyperparathyroidism

BP 160/110 150/80 Clonidine (Catapres) 75 mcg SL Normal CBC, chest xray

Urinalysis 11/14Color Yellow

Transparency Hazy

pH 6.0

Specific gravity 1.025

Sugar Negative

Protein +3Ketones Negative

Nitrites Negative

Leucocyte esterase Negative

Blood +3RBC 19WBC 4

Epithelial cells 6

Bacteria 9

Uric acid crystals moderate

11/14Na 141K 3.3Ca 8.18Corrected Ca 10.02SGOT 40SGPT 55Alk phos 78Total bili 0.30Uric acid 7.0Total protein 5.3Albumin 1.7Cholesterol 245.87

BUN 28.99Creatinine 2.8Glucose 97.01Globulin 3.6A/G Ratio 0.47HDL 42.95Triglycerides 186.2LDL 147.41

Proteinuria, HypoalbuminemiaHyperlipidemiaActive urinary sedimentsHistory of edema

Nephrology referralImpression: Nephrotic syndrome

Acute GN vs chronic GN R/O RPGN

KUB ultrasound24 hour urine collectionESR, CRP, ASO, ANA, C3, HbsAg, Anti Hbs, Anti HCV, anti HIV

• KUB Ultrasound: Bilateral renal parenchymal disease. Normal urinary bladder.

• 24 hour urine collectionUrine Creatinine: 105.4 mgs% = 1370.20

mgs/24hrsUrine protein: 740.2 mgs% = 9622.60

mgs/24hrsTotal volume 1300ml/24hrsSp.gr. 1.020

ESR 60 CRP negative ASO less than 200 ANA negative C3 normal Anti HIV negative

CT scan guided kidney biopsy (+) Anti HCV GI referral Ultrasound of upper abdomen

Minimal ascites. Gallbladder polyp. Normal liver, biliary tree, pancreas and spleen.

RNA virus

WHO, the global prevalence averages 3%, 170M worldwide

6 genotypes ◦ Genotype 1: longer

duration of treatment

Intravenous drug use / needle stick injury Blood transfusion Intranasal cocaine use Hemodialysis HCV-positive mother Sexual transmission History of tattooing and/or body

piercing

HCV genotype

Exposure

Acute Infection

Chronic hepatitis C(50-80%)

Spontaneous resolution(20-50%)

Chronic hepatitis C

Cirrhosis Extrahepatic

Hepatocellular carcinoma(1-4% per

year)

Extrahepatic

Hematologic

diseases

Diabetes Mellitus

Dermatologiccondition

Autoimmune

disordersRenal disease

There is a strong and likely causal association between chronic hepatitis C virus (HCV) infection and glomerular disease

3 types: Mixed Cryoglobulinemia Membranoproliferative glomerulonephritis

(MPGN) Membranous nephropathy

Discharged Pending kidney biopsy, HCV RNA, and HCV

genotype results Home meds:

Atorvastatin 20 mg daily at bedtimeAmlodipine 10 mg dailyPrednisone 10 mg 3 x day

BP 140/90 (+) grade 2 bipedal edema Repeat SGPT: normal Creatinine 2.3 Proteinuria +3, Hematuria +3 HCV RNA: 9,737,233 IU/mL HCV genotype: genotype 1

The presence of subepithelial electron-dense deposits and tubuloreticular structure in this biopsy with strong C1q staining in glomeruli suggests a diagnosis of lupus nephritis. Other conditions with tubuloreticular structures include viral infections (hepatitis and HIV) and alpha-interferon treatment.

(1) Membranous Glomerulopathy, stage I(2) Acute and chronic tubulointerstitial nephritis

29, M Hypertension Hepatitis C glomerulonephritis HCV RNA: 9,737,233 IU/mL HCV genotype: genotype 1 Normal SGPT Estimated creatinine clearance 31 ml/min

Ribavirin anemia gout nasal congestion itchiness

Pegylated Interferon influenza like

symptoms thrombocytopenia leukopenia depression thyroiditis

Goal: viral clearance

Pegylation refers to the cross-linking of polyethylene glycol (PEG) molecules to the interferon molecule, which delays renal clearance.

Advantage of pegylation is that it permits less frequent dosing (once weekly versus three times a week with non-pegylated interferon)

Nucleoside analog which has a broad spectrum of antiviral activity.

It inhibits the replication of RNA viruses in cell culture. It appears to decrease hepatitis C virus infectivity in a dose-dependent manner

Pt M 29 GN, NS Negative

Pt Membranous nephropathy

Pt 1 Peginf-alfa-2b + ribavirin

6 patients became HCV RNA PCR negative and 4 of 7 have maintained both virological and renal remission. 1 of 7 has maintained virological and partial renal

remission 1 patient did not tolerate interferon, but is in

renal remission with low dose ribavirin

Bruchfeld, A. et al. Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant (2003) 18: 1573-1580

1 vasculitis patient responded with complete remission but relapsed virologically and had a minor vasculitic flare after 9 months

1 patient with vasculitis had low dose immunosuppresion in addition to antiviral therapy

serum HCV RNA HCV genotype Baseline liver biochemistry, renal function,

CBC, thyroid function Psychiatric evaluation Pregnancy test

Blood counts and aminotransferases: weeks 1, 2, and 4 and at 4- to 8-week intervals thereafter.

At 24 weeks: aminotransferase levels and HCV RNA. If HCV RNA still present, stop therapy. In patients with genotype 1, stop therapy if HCV

RNA is still positive. Continue therapy for a total of 48 weeks if HCV RNA is negative, and retesting for HCV RNA at the end of treatment.

strict birth control during therapy and for 6 months thereafter.

thyroid-stimulating hormone levels every 3 to 6 months

End of therapy: HCV RNA

• aminotransferases every 2 months for 6 months.• Six months after stopping therapy, test for HCV RNA by PCR.

Peg Intron (peginterferon alfa-2b

Pegasys(peginterferon alfa-2a)

P 730,200Rebetol (Ribavirin) 1200mg dailyP 890,050

PEG-Intron plus Rebetol

(peginterferon alfa-2b + ribavirin)

P 1,620,250

P 698,400Copegus (Ribavirin)1200 mg dailyP 510,400

Pegasys plus Copegus

(peginterferon alfa-2a + ribavirin)

P 1,208,800

No vaccine or immune globulin products available

Screening and testing of blood, plasma, organ, tissue and semen donors

Adequate sterilization of reusable material such as surgical or dental instruments

Needle and syringe exchange programs

Centers for Disease Control and Prevention (CDCP)◦ Ever injected illegal drugs◦ Received clotting factors made before 1987◦ Received blood/organs before July 1992◦ Were ever on chronic hemodialysis◦ Have evidence of liver disease

National Institutes of Health (NIH)◦ multiple sexual partners◦ spouses or household contacts of HCV-infected

patients◦ those who share instruments for intranasal

cocaine use

Hepatitis C related GlomerulonephritisHypertension stage IIDyslipidemias/p kidney biopsy