Disease Awareness Detailer:

Fatigue, pruritus, jaundice, nausea, right upper-quadrant pain

Hepatocellular Carcinoma (HCC)
Hepatitis: inflammation of liver, body response to injury/pathogen (release of
chemicals, swelling, redness)
Chronic hepatitis: low level of inflammation, persistent, preceded by acute hepatitis
(less than 6 months)
Hep A: more acute, self-limiting, vaccine available
Hep B: 5% progress to chronic, vaccine available
Hep C: 85% progress to chronic, vaccine not available
Hep D: satellite infection; propagate only in presence of Hep B
Hep E: not common
Chronic infection: typically no symptoms but may have fatigue
Acute Infection: most have no discernible symptoms
Raised ALT, 2-3x ULN
ALT indicate underlying injury
Advanced Chronic Infection (ESLD): portal hypertension, ascites, encephalopathy,
gastrointestinal bleeding
Transmission: IV drug use, transfusion, hemodialysis
Asia: HCV prevalence 1-3%
Middle East: Genotype 4
Mongolia: 11%
Hepacivirus, RNA virus
Hep B is DNA virus
HCV is a positive sense, single stranded RNA virus
Non-structural proteins (NS)
NS5A-5B: replication complex

NS3/4A: protease
Serine protease inhibitor: previr
NS5A polymerase inhibitor: pasvir, tasvir
NS5B polymerase inhibitor: buvir
Non-nucleoside analogs: less potent, prone to resistance
Daclatasvir: nucleoside analog
Sofosbuvir: nucleoside analog
Viekira: contraindicated in decompensated liver disease
Annual physical examination, attempted blood donation
Hepatocellular, cholestatic (bilirubin), mixed pattern
ALT more specific than AST
Cholestatic: Alkaline phosphatase, GGT
Anti-HCV negative, HCV RNA positive: acute infection (antibodies not synthesized
yet)
Liver biopsy
F0: no fibrosis
F4: cirrhosis, nodules
Fibroscan, Fibrotest/Fibrosure
FIbroscan: transient elastography
RVR: HCV RNA negative <50IU/ml at treatment week 4
Null response: <2 log decrease in HCV RNA
Partial response: >=2 log decrease in HCV RNA
Viral Breakthrough: reappearance of HCV RNA while still on therapy after virologic
response
Relapse: reappearance of HCV RNA in serum after therapy is discontinued, before
SVR12

Pan-genotypic:
PI (ABT-493)
NS5A (ABT-530)
Treatment-nave, non-cirrhotic patients: easy to treat
-Sapphire-I: 631 patients, SVR12 (12 weeks after discountinue of treatment)
Intention to treat analysis vs per protocol analysis
Any AEs compared to placebo
SAEs: pregnant, death/life-threatening, hospitalization, disability
Any AEs leading to discontinuation of study drug is very low
Hyperbilirubinemia w/o ALT increasing, indirect cause of hyperbilirubinemia
Pearl-III: treatment-nave, non-cirrhotic, genotype Ib, +/- ribavirin
Pearl-IV: treatment-nave, non-cirrhotic, genotype Ia, +/- ribavirin
Ritonavir increase concentration of tacrolimus and cyclosporine
Reducing dose of ribavirin to treat anemia
Turquoise-I: HIV co-infection, receiving raltegravir or atazanavir
Ruby-I: renal impaired, 200 mg ribavirin for genotype Ia (to reduce anemia).
Kidney impaired patients: low erythropoietin
Sofosbuvir cannot be used in renal impaired
GT3 is difficult to treat
Harvoni does not interact with immunosuppressant