Michelle B. Moreno, M.D.

To present a case of a young patient with hypertensionTo discuss hepatitis C, its prevalence, diagnosis, evaluation, prevention and extrahepatic manifestationsTo present the treatment option for this case

G.P.29 year old maleFilipinoElevated 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 dayOccasional alcoholic drinker1 sexual partner(+) tattoo on left leg and arm x 1 yearNo illicit drug use

Conscious, coherent, not in respiratory distressBP 160/110HR 86RR 17T 36.9Good skin turgor, no skin lesions, Anicteric sclerae, pink palpebral conjunctivae, no lymphadenopathy, no masses, no neck vein distention, JVP 8, no carotid bruitSymmetrical 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 S4Flat, 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,Muncontrolled blood pressureKnown HypertensiveBP 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 SLNormal CBC, chest xray

Urinalysis11/14ColorYellowTransparencyHazypH6.0Specific gravity1.025SugarNegativeProtein+3KetonesNegativeNitritesNegativeLeucocyte esteraseNegativeBlood+3RBC19WBC4Epithelial cells6Bacteria9Uric acid crystalsmoderate

11/14Na141K3.3Ca8.18Corrected Ca10.02SGOT40SGPT55Alk phos78Total bili0.30Uric acid7.0Total protein5.3Albumin1.7Cholesterol245.87

BUN28.99Creatinine2.8Glucose97.01Globulin3.6A/G Ratio0.47HDL42.95Triglycerides186.2LDL147.41

Proteinuria, HypoalbuminemiaHyperlipidemiaActive urinary sedimentsHistory of edemaNephrology 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 60CRPnegativeASOless than 200ANAnegativeC3normalAnti HIV negative

CT scan guided kidney biopsy(+) Anti HCV GI referralUltrasound of upper abdomenMinimal 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 injuryBlood transfusionIntranasal cocaine useHemodialysisHCV-positive motherSexual transmissionHistory of tattooing and/or body piercing

HCV genotype

ExposureAcute InfectionChronic hepatitis C(50-80%)

Spontaneous resolution(20-50%)

Chronic hepatitis CCirrhosisExtrahepaticHepatocellular carcinoma(1-4% per year)

ExtrahepaticHematologic diseasesDiabetes MellitusDermatologicconditionAutoimmune disordersRenal disease

There is a strong and likely causal association between chronic hepatitis C virus (HCV) infection and glomerular disease3 types: Mixed Cryoglobulinemia Membranoproliferative glomerulonephritis (MPGN) Membranous nephropathy

DischargedPending kidney biopsy, HCV RNA, and HCV genotype resultsHome meds:Atorvastatin 20 mg daily at bedtimeAmlodipine 10 mg dailyPrednisone 10 mg 3 x day

BP 140/90(+) grade 2 bipedal edemaRepeat SGPT: normalCreatinine 2.3Proteinuria +3, Hematuria +3HCV RNA: 9,737,233 IU/mLHCV 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, MHypertensionHepatitis C glomerulonephritisHCV RNA: 9,737,233 IU/mLHCV genotype: genotype 1Normal SGPTEstimated 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

PtM 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 RNAHCV genotype Baseline liver biochemistry, renal function, CBC, thyroid functionPsychiatric 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 availableScreening and testing of blood, plasma, organ, tissue and semen donorsAdequate sterilization of reusable material such as surgical or dental instrumentsNeedle and syringe exchange programs

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

National Institutes of Health (NIH)multiple sexual partnersspouses or household contacts of HCV-infected patientsthose who share instruments for intranasal cocaine use

Hepatitis C related GlomerulonephritisHypertension stage IIDyslipidemias/p kidney biopsy

****************Corrected Ca 10.02*******Risk is quite small, estimated at one in 1.9 million

*****Other glomerular lesions have been reported including focal segmental glomerular sclerosis, proliferative Glomerulonephritis, and fibrillary and immunotactoid glomerulopathies.In some patients, glomerular disease may be clinically silent

********, The desired end-point of treatment of HCV infection is, as indicated by non-detectability of HCV-RNA.*Both are Type I alfa interferons, but differ in size and structure of the interferonand polyethylene glycol molecules, as well as in pharmacokinetic properties (Table 2).16 Onepegylated interferon consists of 31-kilodalton (kDa) interferon alfa-2b conjugated to 12-kilodalton (kDa) polyethylene glycol (trade name PEG-intron). The other consists ofrecombinant 20-kDa interferon alfa-2a linked to 40-kDa polyethylene glycol (trade namePegasys). The dosing schedule is fixed for pegylated interferon alfa-2a and is based on weightfor pegylated interferon alfa-2b.*********In the study, the average daily Ribavirin dose was 200 800 mg The recommended dose for patients with normal renal function is 800 1200 mg

*****Effective birth control should be continued for at least 6 months for patients who have taken ribavirin.If HCV RNA still negative, the chance for a long-term "cure" is excellent; relapses have rarely been reported after this point.

*Doses are 50 g, 80 g, 120 g and 150 g. For simplicity we will use one dose for Peg-Intron (150 g), since the average patient with hepatitis C in the United States weighs between 86-105 Kg (188-231 lbs) and 150 g is the recommended dose for this weight range, plus a fixed dose of Rebetol (1200 mg daily). For Pegasys the amount will be 180 g (all body weights) and for Copegus, 1200 mg daily, for a treatment period of one year, in order to compare the costs of these two combinations.Wholesale Acquisition Cost (WAC), 48 weeks of therapy for Peg-Intron (the standard period of time for treating genotype 1 patients, which is the majority of people with HCV in the United States)

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