Ambulatory ConferenceAmbulatory Conference

Vishal Tiwari PGY 2Vishal Tiwari PGY 2

Thursday 22 May 2008Thursday 22 May 2008

Q Q A 44-year-old man was recently found to have abnormal serologic test results A 44-year-old man was recently found to have abnormal serologic test results for viral hepatitis when he attempted to donate blood. The patient is for viral hepatitis when he attempted to donate blood. The patient is asymptomatic. He used injection drugs and drank alcohol excessively for 2 asymptomatic. He used injection drugs and drank alcohol excessively for 2 years 25 years ago but has not used either drugs or alcohol since. Medical years 25 years ago but has not used either drugs or alcohol since. Medical history is otherwise unremarkable, and he takes no medications. history is otherwise unremarkable, and he takes no medications.

Physical examination discloses a BMI of 23, no stigmata of chronic liver disease, Physical examination discloses a BMI of 23, no stigmata of chronic liver disease, and a normal-sized liver.and a normal-sized liver.

Laboratory StudiesLaboratory StudiesSerum aspartate aminotransferase 53 U/LSerum aspartate aminotransferase 53 U/LSerum alanine aminotransferase 64 U/L Serum alanine aminotransferase 64 U/L Serum alkaline phosphatase 89 U/LSerum alkaline phosphatase 89 U/LSerum total bilirubin 0.9 mg/dL (15.39 Serum total bilirubin 0.9 mg/dL (15.39

μmol/L)μmol/L)Hepatitis B surface antigen (HbsAg) NegativeHepatitis B surface antigen (HbsAg) NegativeAntibody to hepatitis B surface antigen (anti-HBs ) Positive Antibody to hepatitis B surface antigen (anti-HBs ) Positive IgG antibody to hepatitis B coreantigen (IgG anti-HBc) Positive IgG antibody to hepatitis B coreantigen (IgG anti-HBc) Positive IgM antibody to hepatitis B core antigen (IgM anti-HBc) NegativeIgM antibody to hepatitis B core antigen (IgM anti-HBc) NegativeAntibody to hepatitis C virus (anti-HCV) PositiveAntibody to hepatitis C virus (anti-HCV) Positive

Abdominal ultrasonography is normalAbdominal ultrasonography is normal..

Which of the following diagnostic studies Which of the following diagnostic studies should be done next?should be done next?

A Hepatitis B e antigen (HBeAg) A Hepatitis B e antigen (HBeAg)

B Hepatitis B virus DNA (HBV DNA)B Hepatitis B virus DNA (HBV DNA)

C Hepatitis C virus RNA (HCV RNA) C Hepatitis C virus RNA (HCV RNA)

D IgM antibody to hepatitis A virus (IgM D IgM antibody to hepatitis A virus (IgM anti-HAV)anti-HAV)

Source of presentationSource of presentation

Data supported approach, based onData supported approach, based on1.1. A formal review and analysis of recently A formal review and analysis of recently

published world literature topic (medline)published world literature topic (medline)2.2. ACP Manual for assessing health practices ACP Manual for assessing health practices

and designing practice guidelinesand designing practice guidelines3.3. AASLD guideline policiesAASLD guideline policies4.4. Medstudy and MKSAP 14Medstudy and MKSAP 14 Presentation article is fully endorsed by Presentation article is fully endorsed by

the AASLD, IDSA and American College of the AASLD, IDSA and American College of GastroenterologyGastroenterology

Hepatitis C is the leading cause of Hepatitis C is the leading cause of Chronic liver disease Chronic liver disease

CDC estimates at least 3.2 million CDC estimates at least 3.2 million people in US have chronic HCV infectionpeople in US have chronic HCV infection

Hepatitis C is the leading cause of death Hepatitis C is the leading cause of death from liver disease in USfrom liver disease in US

Hepatitis C is the leading indication for Hepatitis C is the leading indication for liver transplantation in the United States liver transplantation in the United States

Hepatitis CHepatitis C

ScreeningScreening IVDA in the recent and remote past, including those whose injected once and don’t IVDA in the recent and remote past, including those whose injected once and don’t

consider themselves to be IVDAconsider themselves to be IVDA Persons with conditions associated with a high prevalence of HCV infection includingPersons with conditions associated with a high prevalence of HCV infection including - HIV infection- HIV infection - Hemophilics who received clotting factor concentrate before 1987 - Hemophilics who received clotting factor concentrate before 1987 - Ever on Hemodialysis- Ever on Hemodialysis - Unexplained abnormal aminotransferase levels- Unexplained abnormal aminotransferase levels Prior recipients of transfusion or organ transplants,inclPrior recipients of transfusion or organ transplants,incl - blood product recepient who later notified with donor tested - blood product recepient who later notified with donor tested positive for HCV infectionpositive for HCV infection - Transfusion of blood or blood products before July 1992- Transfusion of blood or blood products before July 1992 - Organ transplant before July 1992- Organ transplant before July 1992 Children born to HCV infected motherChildren born to HCV infected mother Health care, emergency medical and public safety workers after a needle stick injury Health care, emergency medical and public safety workers after a needle stick injury

or mucosal exposure to HCV positive bloodor mucosal exposure to HCV positive blood Current sexual partners of HCV infected persons ( - ve test for partner reassurance, Current sexual partners of HCV infected persons ( - ve test for partner reassurance,

making testing of sexual partners of benefit in clinical practice)making testing of sexual partners of benefit in clinical practice)

““Rule of 2’s”Rule of 2’s”

2% of US population2% of US population2% risk of needlestick transmission 2% risk of needlestick transmission

(?5%)(?5%)2% risk of neonatal transmission (?2% risk of neonatal transmission (?

5%)5%)2% risk of spousal transmission2% risk of spousal transmission2% cirrohotics with Hep C develop 2% cirrohotics with Hep C develop

Hepatoma each yearHepatoma each year

Q. A 38-year-old man with HIV infection and hepatitis C is Q. A 38-year-old man with HIV infection and hepatitis C is evaluated after moving to a new city. HIV infection and hepatitis evaluated after moving to a new city. HIV infection and hepatitis C were diagnosed 1 year ago, at which time his CD4 cell count C were diagnosed 1 year ago, at which time his CD4 cell count was 523/μL (0.523 × 109/L), and his plasma HIV RNA viral load was 523/μL (0.523 × 109/L), and his plasma HIV RNA viral load was 8522 copies/mL. The patient has remained asymptomatic, was 8522 copies/mL. The patient has remained asymptomatic, and his previous physician did not recommend antiretroviral and his previous physician did not recommend antiretroviral therapy. therapy.

On physical examination at today's visit, he appears well. His On physical examination at today's visit, he appears well. His liver is not enlarged, his spleen is not palpable, and there are no liver is not enlarged, his spleen is not palpable, and there are no signs of liver disease. The remainder of the examination is signs of liver disease. The remainder of the examination is normal.normal.

Laboratory StudiesLaboratory Studies

CD4 cell count 449/μL (0.449 × 109/L)CD4 cell count 449/μL (0.449 × 109/L) Plasma HIV RNA viral load 12,220 copies/mLPlasma HIV RNA viral load 12,220 copies/mL Liver chemistry studies NormalLiver chemistry studies Normal Serum albumin NormalSerum albumin Normal Prothrombin time NormalProthrombin time Normal

Which of the following is the most Which of the following is the most appropriate management of this appropriate management of this patient's hepatitis C at this time? patient's hepatitis C at this time?

A Qualitative hepatitis C virus RNA viral A Qualitative hepatitis C virus RNA viral

load testing load testing

B Liver biopsy B Liver biopsy

C Pegylated interferonC Pegylated interferon

D Pegylated interferon and ribavirinD Pegylated interferon and ribavirin

Lab TestingLab Testing

Initially anti HCV ( EIA/ELISA) is tested.Initially anti HCV ( EIA/ELISA) is tested.Diagnostic “Gold Standard” HCV RNA Diagnostic “Gold Standard” HCV RNA Quantitative RNA-useful in monitoring Quantitative RNA-useful in monitoring

treatment.treatment.Qualitative HCV RNA is more sensitive Qualitative HCV RNA is more sensitive

* some experts use qualitative test as the primary test or to confirm a positive anti HCV test* some experts use qualitative test as the primary test or to confirm a positive anti HCV test

A negative qualitative RNA test in the A negative qualitative RNA test in the presence of HCV antibodies most presence of HCV antibodies most likely indicate that HCV infection has likely indicate that HCV infection has resolvedresolved

Anti HCV DOES not confer immunity Anti HCV DOES not confer immunity (as does the HBV Ab to HB)(as does the HBV Ab to HB)

Assays for HCV RNAAssays for HCV RNA

Qualitative AssaysQualitative Assays HCV RNA can be detected in the blood HCV RNA can be detected in the blood

using amplification techniques such as using amplification techniques such as PCR or TMA ( transcription mediated PCR or TMA ( transcription mediated amplication)amplication)

Quantitative AssaysQuantitative Assays Ascertain the quantity of HCV RNA in blood Ascertain the quantity of HCV RNA in blood

using either target amplification using either target amplification (PCR,TMA) or signal amplification (PCR,TMA) or signal amplification techniques ( branched DNA assay)techniques ( branched DNA assay)

..

HCV GenotypingHCV Genotyping

There are 6 major genotypesThere are 6 major genotypesAlthough genotype does not predict Although genotype does not predict

the outcome of infection, it does the outcome of infection, it does predict the likelihood of treatment predict the likelihood of treatment response, and, in many cases, response, and, in many cases, determines the duration of treatmentdetermines the duration of treatment

Most HCV infection in US are Most HCV infection in US are Genotype 1Genotype 1

Liver BiopsyLiver Biopsy

Role is currently debatedRole is currently debated Bx is NOT necessary for diagnosisBx is NOT necessary for diagnosis Bx is helpful in assessing disease severityBx is helpful in assessing disease severity Bx can aid in decisions about treatment and Bx can aid in decisions about treatment and

surveillancesurveillance Normal LFTs does not preclude a liver Normal LFTs does not preclude a liver

biopsy.biopsy. But Biopsy in not mandatory in order to But Biopsy in not mandatory in order to

initiate Rx. ( Sero marker for cirrhosis in initiate Rx. ( Sero marker for cirrhosis in process)process)

Utility of Liver BiopsyUtility of Liver Biopsy

Liver BiopsyLiver Biopsy A- Portal stage 1 fibrosisA- Portal stage 1 fibrosis

B- Peri-portal stage 2 fibrosisB- Peri-portal stage 2 fibrosis

C-Septal stage 3 fibrosisC-Septal stage 3 fibrosis D- Bridging fibrosis with nodular D- Bridging fibrosis with nodular

regenerationregeneration

Genotype and liver BiopsyGenotype and liver Biopsy

HCV genotype-1 infectionHCV genotype-1 infectionLiver biopsy to guide Liver biopsy to guide

recommendations for treatment.recommendations for treatment.

HCV genotype-2 & 3HCV genotype-2 & 3Have a high likelihood of Rx responseHave a high likelihood of Rx responseTreatment regardless of severity of Treatment regardless of severity of

liver disease without liver biopsy.liver disease without liver biopsy.

Characteristics of persons for Characteristics of persons for whom therapy is widely whom therapy is widely

acceptedaccepted Age at least 18 yearsAge at least 18 years

Abnormal ALT valuesAbnormal ALT values

Liver Bx showing chronic Hepatitis with significant fibrosisLiver Bx showing chronic Hepatitis with significant fibrosis

Compensated liver disease Compensated liver disease (Bili <1.5 g/dl, INR<1.5 Alb>3.4 g/dl, Plt ct > 75K and no evidence of Hepatic Encephalopathy or ascitis)(Bili <1.5 g/dl, INR<1.5 Alb>3.4 g/dl, Plt ct > 75K and no evidence of Hepatic Encephalopathy or ascitis)

Acceptable Hematological and biochemical indicesAcceptable Hematological and biochemical indices (Hb>13 for Men and > 12g/dl for women, Neutrophil > 1.5k/mm3 Cr<1.5 mg/dl)(Hb>13 for Men and > 12g/dl for women, Neutrophil > 1.5k/mm3 Cr<1.5 mg/dl)

Treated previously for HCV infectionTreated previously for HCV infection

History of depression but the condition is well controlledHistory of depression but the condition is well controlled

Willing to be treated and to conform to Rx requirementWilling to be treated and to conform to Rx requirement

Note: All patients have detectable HCV RNANote: All patients have detectable HCV RNA

Treatment RecommendationsTreatment Recommendations

Peginterferon + RibavarinPeginterferon + Ribavarin Indicated in those with more than Indicated in those with more than

portal fibrosis, if histology available.portal fibrosis, if histology available. Rx is individualized based onRx is individualized based on

Severity of liver diseaseSeverity of liver disease Potential of serious side effectsPotential of serious side effects Likelihood of treatment responseLikelihood of treatment response Presence of comorbid conditionsPresence of comorbid conditions

Optimal HCV treatmentOptimal HCV treatment

Combination Peginterferon Regimens with RibavarinCombination Peginterferon Regimens with Ribavarin

Peginterferon alfa-2a(40 kd) 180 mcg SQ q weekly Peginterferon alfa-2a(40 kd) 180 mcg SQ q weekly

regardless of weightregardless of weight

Peginterferon alfa-2b(12kd) 1.5 mcg/kg SQ q weeklyPeginterferon alfa-2b(12kd) 1.5 mcg/kg SQ q weekly

Ribavarin 800 – 1200 mg PO dailyRibavarin 800 – 1200 mg PO daily

( in 2 divided doses), ( in 2 divided doses),

dose depending on infection, dose depending on infection,

genotype, and patientgenotype, and patient weightweight

Genotype 1 HCV infectionGenotype 1 HCV infection

Peginterferon + Ribavarin for 48 Peginterferon + Ribavarin for 48 weeks, ribavarin doses 1 gm for weeks, ribavarin doses 1 gm for those <= 75 kg those <= 75 kg

1.2 gm those >= 75 kg1.2 gm those >= 75 kg

Quantitative serum HCV RNA at the Quantitative serum HCV RNA at the initiation of, or shortly before initiation of, or shortly before treatment and at week 12 of therapy.treatment and at week 12 of therapy.

Genotype-2 or Genotype -3 Genotype-2 or Genotype -3 infectioninfection

Peginterferon + ribavarin for 24 wks, Peginterferon + ribavarin for 24 wks, ribavarin dose of 800 mg.ribavarin dose of 800 mg.

Measure qualitative HCV RNA.Measure qualitative HCV RNA. If -ve,retest for HCV RNA in 24 wks to If -ve,retest for HCV RNA in 24 wks to

document Sustained Virologic document Sustained Virologic Response.Response.

Q A 36-year-old asymptomatic woman who is a phlebotomist is Q A 36-year-old asymptomatic woman who is a phlebotomist is evaluated 12 weeks after having sustained a needlestick injury while evaluated 12 weeks after having sustained a needlestick injury while drawing blood from a patient known to be infected with hepatitis C drawing blood from a patient known to be infected with hepatitis C virus. After the injury, baseline laboratory studies showed the patient virus. After the injury, baseline laboratory studies showed the patient to be negative for hepatitis C virus and HIV. She has a history of to be negative for hepatitis C virus and HIV. She has a history of hypothyroidism and self-limited depression 5 years ago after the hypothyroidism and self-limited depression 5 years ago after the sudden death of her father; her only current medication is sudden death of her father; her only current medication is levothyroxine.levothyroxine.

On physical examination, her vital signs are normal. There is mild On physical examination, her vital signs are normal. There is mild

diffuse enlargement of the thyroid gland; the liver span is normal, and diffuse enlargement of the thyroid gland; the liver span is normal, and there is no splenomegaly or stigmata of chronic liver disease. there is no splenomegaly or stigmata of chronic liver disease.

Laboratory StudiesLaboratory Studies

Complete blood count NormalComplete blood count NormalAlbumin 4.1 g/dL (41 g/L)Albumin 4.1 g/dL (41 g/L)Thyroid-stimulating hormone 3.5 μU/mL (3.5 mU/L)Thyroid-stimulating hormone 3.5 μU/mL (3.5 mU/L)Alanine aminotransferase 900 U/LAlanine aminotransferase 900 U/LBilirubin, total 1.7 mg/dL (29.1 Bilirubin, total 1.7 mg/dL (29.1

μmol/L)μmol/L)Anti-HCV PositiveAnti-HCV PositiveHCV RNA 60,000 IU/MlHCV RNA 60,000 IU/Ml HCV genotype 1bHCV genotype 1bAnti-HBs PositiveAnti-HBs Positive

The INR is normal; HBsAg, anti-HBc, and HIV are all negativeThe INR is normal; HBsAg, anti-HBc, and HIV are all negative

Which of the following is the most Which of the following is the most appropriate next step in the appropriate next step in the management of this patient?management of this patient?

A Therapy with entecavirA Therapy with entecavirB Remeasurement of HCV RNA in 6 B Remeasurement of HCV RNA in 6

monthsmonthsC Hepatic ultrasonography and C Hepatic ultrasonography and

measurement of serum α-fetoprotein measurement of serum α-fetoprotein D Therapy with pegylated interferon D Therapy with pegylated interferon E Hepatitis C recombinant immunoblot assay E Hepatitis C recombinant immunoblot assay

(RIBA)(RIBA)

Adverse Events : Interferon AlfaAdverse Events : Interferon Alfa

HematologicHematologicNeutropeniaNeutropeniaThrombocytopeniaThrombocytopeniaAplastic anemiaAplastic anemia

AutoimmuneAutoimmuneITPITPTTPTTP

EndocrineEndocrineHypothyroidismHypothyroidismHyperthyroidismHyperthyroidism

Neuro-PsychNeuro-PsychDepressionDepressionIrritability Irritability Concentration and memory Concentration and memory

disturbancesdisturbancesVisual disturbancesVisual disturbancesFatigueFatigueMuscle achesMuscle achesHeadachesHeadachesNausea vomitingNausea vomiting

RibavarinRibavarin

Hemolytic anemiaHemolytic anemiaFatigueFatigue ItchingItchingRashRashSinusitisSinusitisBirth defectsBirth defectsGoutGout

Adverse EventsAdverse Events

DeathsDeaths reported with INF-Alfa and reported with INF-Alfa and Ribavarin include Suicide, MI, Sepsis Ribavarin include Suicide, MI, Sepsis and Strokeand Stroke

Q. An 84-year-old man comes for a follow-up visit after being diagnosed with Q. An 84-year-old man comes for a follow-up visit after being diagnosed with hepatitis C. Liver chemistry tests are abnormal, and serum HCV RNA is hepatitis C. Liver chemistry tests are abnormal, and serum HCV RNA is positive. Medical history is significant for ischemic cardiomyopathy with an positive. Medical history is significant for ischemic cardiomyopathy with an ejection fraction of 15%. The patient had a blood transfusion 20 years ago at ejection fraction of 15%. The patient had a blood transfusion 20 years ago at the time of coronary artery bypass graft surgery. He has no history of the time of coronary artery bypass graft surgery. He has no history of excessive alcohol intake. excessive alcohol intake.

On physical examination, he appears chronically ill. Pulse rate is 80/min, On physical examination, he appears chronically ill. Pulse rate is 80/min,

and blood pressure is 90/60 mm Hg. There are no stigmata of chronic liver and blood pressure is 90/60 mm Hg. There are no stigmata of chronic liver disease. Jugular venous distention is present. Bibasilar crackles and a disease. Jugular venous distention is present. Bibasilar crackles and a prominent S3 are auscultated. The liver is pulsatile and slightly enlarged. prominent S3 are auscultated. The liver is pulsatile and slightly enlarged. There is no ascites, but mild pedal edema is noted.There is no ascites, but mild pedal edema is noted.

Laboratory StudiesLaboratory Studies Complete blood count NormalComplete blood count NormalSerum aspartate aminotransferase 73 U/LSerum aspartate aminotransferase 73 U/LSerum alanine aminotransferase 84 U/LSerum alanine aminotransferase 84 U/LSerum alkaline phosphatase 132 U/LSerum alkaline phosphatase 132 U/LSerum total bilirubin 1.0 mg/dL (17.1 μmol/L)Serum total bilirubin 1.0 mg/dL (17.1 μmol/L)

Abdominal ultrasonography shows mild hepatomegaly, a normal-sized spleen, Abdominal ultrasonography shows mild hepatomegaly, a normal-sized spleen, and no ascites.and no ascites.

Which of the following is most appropriate Which of the following is most appropriate for managing this patient's hepatitis C at for managing this patient's hepatitis C at this time?this time?

A Liver biopsy A Liver biopsy

B HCV genotyping B HCV genotyping

C Pegylated interferon C Pegylated interferon

D Pegylated interferon and ribavirin D Pegylated interferon and ribavirin

E No further testing or treatmentE No further testing or treatment

Contraindications for Contraindications for TreatmentTreatment

Major, uncontrolled depressive illnessMajor, uncontrolled depressive illness Renal, Heart or Lung transplant recipientRenal, Heart or Lung transplant recipient Autoimmune Hepatitis or other condition known Autoimmune Hepatitis or other condition known

to be exacerbated by interferon and ribavarinto be exacerbated by interferon and ribavarin Untreated HyperthyroidismUntreated Hyperthyroidism Pregnant or unwilling/unable to comply with Pregnant or unwilling/unable to comply with

adequate contraceptionadequate contraception Severe concurrent disease such as severe Severe concurrent disease such as severe

hypertension, heart failure, significant CAD, hypertension, heart failure, significant CAD, poorly controlled DM, Obstructive pulmonary dspoorly controlled DM, Obstructive pulmonary ds

Under 3 years of ageUnder 3 years of age Known hypersensitivity to drugs used to treat Known hypersensitivity to drugs used to treat

HCVHCV

Q. A 22-year-old woman with hepatitis C becomes pregnant for the first Q. A 22-year-old woman with hepatitis C becomes pregnant for the first time. She is at 10 weeks gestation, and the pregnancy has been time. She is at 10 weeks gestation, and the pregnancy has been uneventful. Hepatitis C was diagnosed 5 years ago and was believed uneventful. Hepatitis C was diagnosed 5 years ago and was believed to be acquired following blood transfusions when the patient was 3 to be acquired following blood transfusions when the patient was 3 years old and was being treated for hemolytic uremic syndrome. The years old and was being treated for hemolytic uremic syndrome. The patient is HCV genotype 1 and has an HCV RNA viral load of 3 million patient is HCV genotype 1 and has an HCV RNA viral load of 3 million copies/mL. Liver biopsy 6 months ago showed grade 1 (mild) copies/mL. Liver biopsy 6 months ago showed grade 1 (mild) inflammation and stage 0 (no) fibrosis. inflammation and stage 0 (no) fibrosis.

Physical examination is normal.Physical examination is normal.

Laboratory StudiesLaboratory Studies

Complete blood count NormalComplete blood count NormalLiver enzyme studies NormalLiver enzyme studies NormalSerum albumin NormalSerum albumin NormalINR NormalINR NormalHIV antibody NegativeHIV antibody NegativeHepatitis B surface antigen (HBsAg) NegativeHepatitis B surface antigen (HBsAg) NegativeAntibody to hepatitis B surface antigen (anti-HBs) PositiveAntibody to hepatitis B surface antigen (anti-HBs) Positive

Which of the following is most appropriate?Which of the following is most appropriate?

A Administer pegylated interferon and ribavirin to A Administer pegylated interferon and ribavirin to the mother now the mother now

B Administer pegylated interferon to the mother B Administer pegylated interferon to the mother now now

C Administer pegylated interferon and ribavirin to C Administer pegylated interferon and ribavirin to the infant soon after birth the infant soon after birth

D Check the serum HCV RNA in the infant 4 D Check the serum HCV RNA in the infant 4 months after birthmonths after birth

Steps in managing and treating Steps in managing and treating HCV Genotype 1 SVRHCV Genotype 1 SVR

Steps in managing and treating Steps in managing and treating HCV Genotype 2/3 SVR, ETRHCV Genotype 2/3 SVR, ETR

CounselingCounseling Avoid sharing toothbrushes and dental or shaving equipment Avoid sharing toothbrushes and dental or shaving equipment Cautioned to cover any bleeding wound in order to keep their blood Cautioned to cover any bleeding wound in order to keep their blood

away from othersaway from others Stop using illicit drugs, if continues then should be counseled to Stop using illicit drugs, if continues then should be counseled to

avoid reusing or sharing syringes, needles, water and cotton or avoid reusing or sharing syringes, needles, water and cotton or other paraphernaliaother paraphernalia

Risk of sexual transmission is low and that the infection itself is not Risk of sexual transmission is low and that the infection itself is not a reason to change sexual practices if in long term relationshipa reason to change sexual practices if in long term relationship

Not to donate blood, body organs other tissues or semenNot to donate blood, body organs other tissues or semen

Adapted from CDC recommendations for prevention and control of HCV infectionAdapted from CDC recommendations for prevention and control of HCV infection

Q. A 40-year-old woman has a lower extremity rash that has been Q. A 40-year-old woman has a lower extremity rash that has been present for several months. The patient used injection drugs 18 present for several months. The patient used injection drugs 18 years ago. She was once told that her liver enzyme values were years ago. She was once told that her liver enzyme values were abnormal but did not return for follow-up studies. Medical history abnormal but did not return for follow-up studies. Medical history is otherwise noncontributory.is otherwise noncontributory.

Physical examination is normal except for a palpable purpuric rash Physical examination is normal except for a palpable purpuric rash on her lower extremities. on her lower extremities.

Laboratory StudiesLaboratory Studies

Serum aspartate aminotransferase 63 U/LSerum aspartate aminotransferase 63 U/LSerum alanine aminotransferase 84 U/LSerum alanine aminotransferase 84 U/LSerum alkaline phosphatase 74 U/LSerum alkaline phosphatase 74 U/LHepatitis B surface antigen (HBsAg) NegativeHepatitis B surface antigen (HBsAg) NegativeAntibody to hepatitis B surface antigen (anti-HBs) PositiveAntibody to hepatitis B surface antigen (anti-HBs) PositiveIgG antibody to hepatitis B core antigen (IgG anti-HBc) PositiveIgG antibody to hepatitis B core antigen (IgG anti-HBc) PositiveIgM antibody to hepatitis B core antigen (IgM anti-HBc) IgM antibody to hepatitis B core antigen (IgM anti-HBc)

NegativeNegativeAntibody to hepatitis C virus (anti-HCV) PositiveAntibody to hepatitis C virus (anti-HCV) Positive

Which of the following diagnostic Which of the following diagnostic studies should be done next?studies should be done next?

A Mesenteric angiography A Mesenteric angiography

B Measurement of serum and urine B Measurement of serum and urine porphyrinporphyrin

C Antinuclear antibody assay C Antinuclear antibody assay

D Measurement of serum cryoglobulin D Measurement of serum cryoglobulin

Extra-hepatic complications of Extra-hepatic complications of HCVHCV

Small vessel vasculitis with GN and Small vessel vasculitis with GN and NeuropathyNeuropathy

Mixed cryoglobulinemia- Purple Mixed cryoglobulinemia- Purple purpurapurpura

Porphyria cutanea tardaPorphyria cutanea tarda

ThanksThanks

Dr MathewDr Mathew