Ann IM 2002;136:747; 2000;132:296; Nejm 2001;345:41
Cause:Hepatitis C RNA virus, several genotypes, 1a and 1b most common in US
Pathophys:No protective antibody response develops
1.8% prevalence of antibodies in the US, 4 million infected (Nejm 1999;341:556), but up to 5+% in Africa and Middle East.
Over 50% of cases due to iv drug use; 50-80% of iv drug users contract within 1st yr of use. 97% of post-transfusion hepatitis in US (Nejm 1991;325:1325)
Transfusions, incidence = 1/100 000 transfusions using screened blood (Nejm 1996;334:1685), 18/10 000 using unscreened blood (Nejm 1992;327:369)
Post-organ transplant, eg, renal (Nejm 1992;326:454)
Sexual transmission rates are low but real, eg, 1% annual infection rate in monogamous couples, 2-3% annual incidence in wives of infected hemophiliacs (Ann IM 1994;120:748; 1991;115:764)
Neonatal transmission rate low, 2.5% (Ann IM 1992;117:881, 887) to 5% (Nejm 1994;330:744) as is intrafamilial rate (Jama 1995;274:1459)
Chronic carrier state develops in 85+% after acute infection and lasts years even with normal LFTs (Nejm 1992;327:1899); 75-90% with hep C antibody have viremia (Nejm 1990;323:1107)
Sx:2- to 20-wk incubation, average 6-7 wk; 80% are anicteric
Mixed cryoglobulinemia (Cryoglobulinemia);
B cell non-Hodgkins lymphoma, reversible w rx of Hep C (Nejm 2002;347:89)
CHRONIC HEPATITIS(Nejm 2006;355:2444) in 80% over 10+ yr, 5-15% of whom go on to cirrhosis over 20+ yr; hepatocellular carcinoma 1-4%/yr after onset of cirrhosis; liver biopsy shows fibrosis with bridging between hepatic lobules but pathologic picture waxes and wanes; typically used to guide treatment
Vasculitis of various types
r/o other causes of chronically elevated LFTs: hemochromatosis, Wilson's disease, 
1-antitrypsin deficiency (Nejm 1981;304:558), drug-induced hepatitis from various drugs, primary biliary cirrhosis (Primary Biliary Cirrhosis), alcohol and other toxins, diabetes, myxedema, myopathies
Lab:
Chem:Elevated LFTs, esp SGPT (ALT), but not 100% sens (Ann IM 1995;123:330)
Serol:(Jama 2007;297:724): Anti-hep C virus IgG antibody levels (ELISA) 1st detectable 10-50 wk after exposure and 4-6 wk after LFT elevations appear; hep C viral RNA titer correlates with infectivity and persistence as chronic hepatitis, tested for by PCR (target amplification) method, or more inconsistent branched-chain DNA (signal amplification) assay (Ann IM 1995;123:321) used primarily to monitor rx
Cryoglobulins in 50%
Rx:
Prevent by avoiding high-risk behaviors (iv drugs, sexual promiscuity), body fluid precautions, and by screening donors for anti-HCV levels will prevent 60% (Nejm 1990;323:1107) to 85% of cases; a small % of donors will be infectious but won't yet be antibody positive. Barrier methods of BC probably not necessary in monogamous couples given 1-3% lifetime risk (MMWR 1998;47:1). Prophylaxis with immune globulin is ineffective
Prevent hepatocellular carcinoma w 45 mg po qd vit K2 (menaquinone) impressively effective in initial Japanese study (Jama 2004;292:358)
of disease (Ann IM 2000;133:665) (elevated ALT, viremia and/or cirrhosis on bx); use long-acting interferon and ribavirin, +/or telaprevir; genotype to predict response and determine duration of tx; perhaps w telaprevir? (Nejm 2009;360:1827):
- Interferon-2a or b (Peg-Intron/Pegasys) (Nejm 2009;361:580) q 1 wk w ribavirin, 30% eradication in HIV pts rather than <14%, and 55-65% eradication in immunocompetent pts, $1000/mo, alone × 6 mo in acute disease may prevent chronic hep C infection (Nejm 2001;345:1452)
- Ribavirin (Med Let 1999;41:53; Am J Med 1999;107:112; Lancet 1998;352:1426) (sold w interferon-2b as Rebetron; ways to give w peg-2a available soon) × 6-12 mos depending on hep C genotype (Ann IM 2004;140:346, 370), many side effects and $8000/6 mo, but helps over 50% cost effectively (Am J Med 2000;108:366); not useful alone (Am J Gastroenterology 2006;101:842)
- Protease inhibitors: boceprevir or telaprevir imprdove interferon cure rates (Nejm 2011;364:1195, 1207, 1272; 2010;362:1292; 2009;360:1827)
other options: liver transplant; hep A and B vaccination if not immune already, to prevent frequently fatal hepatitis in chronic hep C (Nejm 1998;338:286)
other notes on rx treatment: decreases incidence of hepatoma × 50% (Ann IM 2005;142:105; 1999;131:174); much more effective in the 25% w a susceptibility gene (Nejm 1996;334:77), much less effective in blacks (19%) than whites (52%) (Nejm 2004;350:2265); NIH CDC suggests checking ALT and RNA levels after 12 weeks rx and stopping if not markedly improved (Ann IM 1997;127:855, 866, 918; Hepatol 1996;24:778). Can reverse cirrhotic fibrosis (Ann IM 2000;132:517)