According to the World Health Organization, 170 million individuals throughout the world are infected with HCV. An estimated 1.8% of the population in the United States is positive for HCV antibodies (anti-HCV) or 3.9 million persons nationwide. Infection due to HCV accounts for 20% of all cases of acute hepatitis, an estimated 30,000 new acute infections, and 15,000 deaths each year in the United States.  No vaccine is available.  Fortunately, most deaths occur many years after initial infection.

Medical care costs associated with the treatment of HCV infection in the United States are estimated to be more than $600 million per year and rapidly increasing due to the high cost of treatment.  Most patients infected with HCV have chronic liver disease, which may progress to cirrhosis and hepatocellular carcinoma. Chronic infection with HCV is one of the most important causes of chronic liver disease. Currently, liver failure from chronic hepatitis C is the most common indication for liver transplantation in the United States.

HCV is spread primarily by IV drug abuse (60%) due to needle sharing.  Tattooing, even in established tattoo parlors, is a significant risk factor. Screening of blood donors since 1990 has decreased the risk of HCV to less than 1 case in 103,000 transfused units. The risk is even lower with the use of more sensitive assays with the polymerase chain reaction (PCR) to screen blood.  In 10% of cases, there are no reported risk factors for infection.  About 5% of infants contract it from their hep C positive mothers at birth.  Intranasal cocaine users can contract it by sharing equipment.  High risk sexual behavior, STDs, and multiple partners are lesser risk factors.  In monogamous couples, the rate of spread for the positive partner is less than 1% per year. 

HCV also may be transmitted by acupuncture, and sharing razors. Needlestick injuries in the health care setting result in a 3% risk of HCV transmission. However, the prevalence of hepatitis C among health care workers is similar to that of the general population. Patient-to-patient transmission has occurred by use of a contaminated colonoscope, dialysis, and surgery, including organ transplantation before 1992. Uncommon routes of transmission of HCV affecting no more than 5% of the individuals at risk, include high-risk sexual activity and maternal-fetal transmission. Casual household contact and contact with the saliva of those infected are inefficient modes of transmission. No risk factors are identified in approximately 10% of cases.

Of those infected with HCV, 70-80% develop chronic infections.  Severe progression of hepatitis C to cirrhosis occurs in approximately 20% of patients who have chronic infection usually taking 10-20 years. Hepatocellular carcinoma develops in 1-4% of patients with cirrhosis each year usually taking 20-40 years after time of infection.  HIV infection and alcoholism each markedly increase the risk of cirrhosis in HCV patients. The number of deaths due to HCV has increased from 9,000 in 1992 to 15,000 in 1999 and is expected to continue to increase due to an increasing rate of chronic infections.

The viral load detected with quantitative assays can be used to predict the outcome of anti-HCV therapy but not the likelihood of disease progression.  The alanine aminotransferase (ALT) level may be elevated in patients with acute hepatitis C, and the ALT level is useful for helping monitor the effectiveness of therapy for HCV infection.  Patients with genotype 1 infection usually are treated for 12 months, compared with 6 months in patients with genotypes 2 and 3. 

Therapy with pegylated IFN alfa (Peg-intron) and the nucleoside analog ribavirin (Rebetol) is the current standard of care in patients who are anti-HCV and HCV RNA positive with elevated liver enzymes and cirrhosis on biopsy.  Peg is polyethylene glycol and INF alfa is recombinant interferon alfa-2b.  Patients with HCV genotype 1 have a less favorable response to therapy and are treated for 12 months, compared with patients infected with genotypes 2 and 3, in whom a 6-month course of therapy is sufficient.  If viremia is present after 6 months, additional therapy has a negligible incremental benefit and treatment should be stopped in all patients regardless of the viral genotype.  Cure rates are about 50%.

The Centers for Disease Control and Prevention estimates that within a decade there will be a 279% increase in the incidence of liver damage nationwide due to hepatitis C, a 528% increase in the need for transplants and a 223% increase in the liver-related death rate.

Vitamin K reduced deaths from liver cancer in hepatitis B and C victims in a recent Japanese study.  There are many lab and animal studies supporting this finding.  I recommend vitamin K to all of my hepatitis B and C patients, whether or not they have had peg-intron and ribirin treatment.  Buy the K-1 with K-2 capsules from iherb.com for $20.21 for 90 capsules or $6.74/month or $84/year.  Coffee also appears to help: drink at least 4 cups a day.  Decaf and tea don't work.  Milk Thistle ($168/year), selenium (200 mcg/day)($16/year), and melatonin (12 mg/night)($50/year) are all probably worthwhile, but have less evidence.  Acetyl-L-carnitine is low in hepatitis C, since it is normally made by the liver.  Supplementation might prevent liver cancer in those with active hepatitis as well as increasing energy.  I recommend 1 gram/day if fatigue is present ($108/year). 

Smoking and alcohol are very bad for HCV patients.  

Hepatitis C Blocks Interferon Regulatory Factor-3, Key to Chronicity: As HCV begins to replicate, it manufactures proteases to transform viral proteins into their functional forms. One, NS3/4A, specifically inhibits a key immune system molecule, interferon regulatory factor-3 (IRF-3). IRF-3 orchestrates a range of antiviral responses. Without this master switch, antiviral responses never begin, and HCV can gain a foothold and persist in its host. Researchers applied a protease inhibitor to human cells containing modified HCV. This prevented the virus from making functional NS3/4A and restored the cells' IRF-3 pathway. Follow-up studies have shown that once restored, the immune response reduced viral levels to nearly undetectable levels within days. University of Texas Southwest, 4/19/03

Peg-interferon & Ribavarin for HCV: Of the 1 million HIV-infected Americans, about 300,000 are also infected with HCV. In a DB PC study, 133 HIV-positive adults took peg-interferon or interferon for 48 weeks. All took ribavirin, a standard antiviral therapy for hepatitis C. With peg-interferon, 27% had no detectable HCV in their blood 24 weeks after completing treatment (sustained response) vs. 12% with interferon. One third of those who failed to clear HCV showed improvement in their liver biopsies. Industry funded. Raymond T. Chung, MGH. NEJM 7/29/04.

Interferon No Benefit for Older HCV Cirrhosis Patients: In a 24-month randomized controlled trial of 102 HCV cirrhosis patients (average age 60), prolonged IFN alfa-2a treatment was of no benefit. During the follow-up evaluation, the complication rate was 24.5%: HCC occurred in 12 and decompensation unrelated to HCC occurred in 13 patients. The number of HCC patients was similar in both groups. The probability of complication-free survival was not significantly different between treated and untreated patients (98% and 72.3% vs 90% and 70.7% at 12 and 24 mo, respectively, P = .59). The median time until complication occurrence was 17.1 months in the treated group vs 13.6 months in the untreated group (P = .2). Effect of Prolonged Interferon Therapy on the Outcome of Hepatitis C Virus-Related Cirrhosis: A Randomized Trial. Fartoux L, et al. Universite Pierre et Marie Curie, Paris, France. Clin Gastroent Hepatol 2007 Jan 26. Ed: This amazing lack of benefit contrasts with major benefit from vitamin K in a similar population.

Cirrhosis More Common After Transplant in Those Treated with Interferon: Up to 30% of HCV patients develop cirrhosis only 5 years after LT in the absence of antiviral therapy. In 105 patients having a transplant, 70 were pre-treated with interferon and/or ribavirin. Recipients with fibrosis >2 (13% at 10 years) had a significantly reduced survival rate (63% vs. 87% at 10 years, P = 0.03). In a multivariate analysis, recipient male gender (P = 0.04), antiviral treatment before LT (P = 0.001), and initial immunosuppressive regimen without azathioprine (P = 0.03) were associated with progression of fibrosis. Factors influencing the progression of fibrosis in patients with recurrent hepatitis C after liver transplantation under antiviral therapy: A retrospective analysis of 939 liver biopsies in a single center. Walter T, et al. Hopital Edouard Herriot, Lyon, France. Liver Transpl 13:294-301, 2007. 

Interferon: Retreatment of Failures is of Margin Benefit: In a study of 20 patients (age 50, 95% genotype 1, 35% cirrhosis, 60% had no prior treatment for Hepatitis C before the first PEG/RBV) who were treated with PEG IFN alpha-2b plus RBV and PEG IFN alpha-2a plus RBV but didn't achieve a sustained response (an early virologic response by week 12 or presence of detectable HCV RNA at week 24 or after completion of PEG-IFN + RBV therapy), after a second course of PEG IFN plus RBV, only 10% achieved a sustained virologic response. These results suggest marginal benefit of retreatment of patients with chronic HCV with another course of PEG IFN plus RBV after they have not responded to an initial course of PEG IFN plus RBV. Pegylated Interferon and Ribavirin Failures: Is Retreatment an Option? Cheruvattath R, et al. Mayo Clinic, Scottsdale, Arizona. Dig Dis Sci 2007 Jan 26.

Interferon: Relapsers Better in Retreatment, But Not Non-Responders: In a study of 101 non-responders and 53 relapsers to standard combination therapy, of those retreated with peginterferon alfa-2b 1.5mug/kg/wk plus ribavirin 1000-1200mg/day during 48 weeks, 29% achieved sustained virological response (SVR). Rapid (week 4) and early (week 12) virological response had high negative predictive values of SVR (94% and 97%, respectively); however positive predictive values were relatively low (52% and 49%, respectively). Relapsers had higher SVR rates (58%) than non-responders (13%) p<0.0001. In non-responders, SVR raised to 50% in patients with genotype non-1 and mild or moderate fibrosis. High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy. Moucari R, et al. Universite Paris VII, France. J Hepatol 2006 Nov 27.

Interferon: Side-Effects of Treatment: Most patients receiving treatment suffer some side-effects with fatigue (68%), headache (63%), and sore muscles (61%) most common.  Other very common side-effects are fever (37%), nausea (38%), insomnia (39%), depression (32%), and joint pain (30%).  In addition to these, hair loss (28%), loss of appetite (27%), irritability (23%), itching (21%) and rash (20%) are quite common.  Difficulty breathing (19%), dizziness (17%), heartburn (14%), vomiting (11%), and difficulty concentrating are also common.  Hemolytic anemia is the big side-effect of treatment and can lead to fatal heart attacks, so hemoglobin levels are monitored closely, especially early in treatment.  Many other side-effects can occur including suicidal thoughts and behavior (1%).  Pancreatitis and pneumonia are less common severe side-effects.  Auto-immune disorders may be aggravated.  Treatment should be done with great caution with patients with pre-existing psychiatric problems with close monitoring.  Pregnant females and male partners of pregnant females cannot use the treatment due to serious risks of birth defects.  Most side-effects are due to the weekly Peg-intron injections rather than due to the twice daily ribavirin pills. (PDR 2005).

Alcohol Major Cause of Early Death From HCV; Worse for Females: Using national mortality data, compared with deaths of HCV without heavy alcohol use (HAU), the mean age of death was shortened for deaths of HCV plus HAU (from 55.1 to 50.0 years among males, and from 61.0 to 49.1 years among females). The cumulative probability of death before age 65 was much higher for the latter than the former group (0.91 vs 0.68 among males, and 0.88 vs 0.47 among females). Alcohol and hepatitis C mortality among males and females in the United States: a life table analysis. Chen CM, et al. CSR, Incorporated, Arlington, Virginia. Alc Clin Exp Res 2007 Feb;31(2):285-92.

Don't Take Ibuprofen; Use Low Dose Tylenol or Glucosamine/Chondroitin for Joint Pain: Hepatitis C victims often have joint pain. Thomas Riley, III, of Penn State's College of Medicine reported three cases of ibuprofen-induced hepatotoxicity in Hepatitis C victims. Am J Gastroenterology 9/98. According to Riley, acetaminophen (Tylenol) 500 mg up to every six hours is a safer treatment for acute pain. Glucosamine and Chondroitin is actually a still safer and much more effective remedy for arthritis (See Arthritis).

Depression Common in HCV Treatment: Interferon-alpha (IFN-alpha) plus ribavirin is used to treat hepatitis C virus (HCV) infection and is associated with a high rate of depression. In a study of 162 HCV-infected patients at baseline and after 24 weeks of treatment with pegylated IFN alpha-2b (PEG IFN) plus weight-based (N = 86) versus standard dose (N = 76) ribavirin, 39% experienced moderate to severe depressive symptoms at some point during therapy. Baseline depression scores significantly predicted severity of depressive symptoms during PEG IFN/ribavirin treatment (p < .0001). In addition, assignment to weight-based ribavirin treatment increased depression risk 170% and history of depression increased the risk 230% (OR = 2.7, p < .01, and OR = 3.3, p < .01). Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. Raison CL, Borisov AS, et al. Emory University. J Clin Psychiatry. 2005 Jan;66(1):41-8.

Etanercept Helped in Small Study as Add-On: In a DB PC study of 50 patients with chronic HCV to receive interferon alfa-2b and ribavirin, HCV RNA was absent in 63% etanercept patients compared to 32% on placebo  (P=0.04). Those on etanercept had lower frequency of most adverse events categories compared to placebo. Etanercept as an adjuvant to interferon and ribavirin in treatment-naive patients with chronic hepatitis C virus infection: a phase 2 randomized, double-blind, placebo-controlled study. Zein NN; Etanercept Study Group. Mayo Clinic, Rochester, MN. J Hepatol. 2005 Mar;42(3):315-22. Ed: It is sad to see the Mayo Clinic researching the very expensive etanercept, very likely funded by the industry, but neglected to research vitamin K.  Thank goodness, medical schools in other countries are not as strong controlled by drug industry funding as are American schools.

Interferon Viral Response Markedly Lowers Liver Cancer: A meta-analysis of eight European follow up studies of interferon treatment for chronic hepatitis C found a total of 286 sustained virological responders and 50 biochemical responders (detectable virus but normal alanine aminotransferase levels). They were followed up for 59 months. The late virological relapse rate after five years of follow up was 4.7% among sustained virological responders; all late relapses occurred within four years after treatment. Among sustained virological responders, the rate of decompensation after five years of follow up was 1.0% and none developed hepatocellular carcinoma (HCC). Survival was comparable with the general population, matched for age and sex. Clinical outcome of patients with cirrhosis was similar to other sustained virological responders. For biochemical responders, the rates of development of decompensation and HCC during long term follow up were 9.1% and 7.1%, respectively. Veldt B, Saracco G, et al. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy. Rotterdam, The Netherlands. Gut. 2004; 53: 1504-1508.

Risk Factors for Liver Cancer: Of 463 patients with cirrhosis of the liver, 38 of whom ultimately developed hepatocellular cancer (HCC). An increased risk of developing HCC included: age 5 or older, antibodies to hepatitis C, lower platelet and lower prothrombin (75% or less). Velazquez R, Rodriguez M, et al. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Spain. Hepatology. 2003;37:520-527. Ed: This study seems to support vitamin K treatment, since vitamin K increases prothombin.

high sustained virological responses can be obtained: >80% in genotypes 2 and 3 and >50% in genotype 1. Treatment in genotypes 2 and 3 should be considered in all patients, whereas in genotype 1 the decision has to be based on the presence of fibrosis in the liver biopsy and general patient characteristics. Hepatitis C should be excluded in all patients with elevated liver enzymes. In risk groups with a high prevalence of hepatitis C, the infection should be looked for even when liver enzymes are normal.

Amantidine May Prevent Interferon/Ribavirin Depression: In a randomized, controlled trial with 14 hepatitis C virus-infected patients, treated with pegylated interferon alfa-2a 180 microg/wk plus ribavirin 1.200 mg/d, 8 were randomized to receive amantadine 200 mg/day. No significant increase in mean Hospital Anxiety and Depression Scale scores of depressive symptoms were seen in amantadine group (P = 0.142), while there was a statistical increase of depression scores in the control group (P = 0.001). Effect of amantadine on depressive symptoms in chronic hepatitis C patients treated with pegylated interferon: a randomized, controlled pilot study. Quarantini LC, et al. Federal University of Bahia, Brazil. . Clin Neuropharmacol 2006 May-Jun;29(3):138-43.

Coffee Appears to Protect Against Cirrhosis Including Viral: Coffee use has consistently been associated with lower serum liver enzyme levels and a reduced risk of liver cirrhosis. Cohort and case-control studies also suggest a decreased risk of hepatocellular carcinoma (HCC) among coffee drinkers. In 209 HCC cases and three different controls (1308 community controls, 275 hospital controls, and 381 patients with chronic liver disease [CLD] without HCC), after adjustment for sex, age, heavy alcohol use, smoking status and hepatitis virus markers (except for community controls), coffee use during the last 1-2 years was associated with a decreased risk against any control group. For coffee use 10 years before, comparison between HCC cases and either community controls or CLD patients revealed a decreased risk; adjusted odds ratios for occasional use, 1-2 cups/day and >/=3 cups/day compared with no use were 0.33, 0.27 and 0.22 (P trend < 0.001), respectively, against community controls, and 0.86, 0.62 and 0.53 (P trend = 0.05), respectively, against CLD patients. Inverse association between coffee drinking and the risk of hepatocellular carcinoma: a case-control study in Japan. Tanaka K, et al. Saga University, Japan. Cancer Sci 2007; 98: 214-218.

Diabetes Increased by Hep C and High Ferritin: In a study of 170 patients positive for Hep C vs. 137 controls, 13% had diabetes with viral RNA, 9.3% in the infected patients without RNA and 3.9% in the controls. The average of the ferritin level for the infected patients was 256 mg/l and for the controls was 151 mg/l (p = 0.01). The diabetic patients had ferritin levels of 346 mg/l and non-diabetic patients had 218 mg/l (p = 0.038). The presence of HCV-antibodies showed a 2.78 odds ratio for diabetes risk. epatitis C as a risk factor of diabetes mellitus type 2. Virseda Chamorro I, et al. Hospital Central de la Defensa Gomez Ulla, Madrid, Espana. . Rev in Esp 2006 Apr;206(4):167-71.

Milk Thistle Sizeable Apparent Benefit in Studies, But Larger Studies Necessary to Prove It: Thirteen randomized clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C liver diseases. Only 23% of the trials reported adequate allocation concealment and only 46% were considered double blind. MT versus placebo or no intervention for a median duration of 6 months had no significant effects on all-cause mortality although mortality was 22% lower with milk thistle (RR 0.78, 95% CI: 0.53-1.15), complications of liver disease, or liver histology. Liver-related mortality was significantly reduced (50%) by MT in all trials (RR 0.50), but not in high-quality trials (43% reduced but no statistically significant (RR 0.57, 95% CI 0.28-1.19). MT was not associated with a significantly increased risk of adverse events. Adequately conducted randomized clinical trials on MT versus placebo may be needed. Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic cochrane hepato-biliary group review with meta-analyses of randomized clinical trials. Rambaldi A, et al. Copenhagen University Hospital, Denmark. Am J Gastroenterol 2005 Nov;100(11):2583-91. Ed: While the author put down milk thistle as ineffective, the decreased mortality was actually quite sizeable.  If larger studies found a similar result, it would be an excellent outcome and valuable therapy.  

Milk Thistle No Help in Small Hepatitis C Study: In a DB PC crossover study of 24 patients with hepatitis C, 12 weeks of Silymarin marianum (either 600 mg or 1200 mg/day) had no significant effect on HCV RNA titers, serum ALT levels or Short Form-36 scores. There was no significant change in mean State-Trait Anxiety Inventory State-Anxiety scores on S. marianum. Adverse events were similar with S. marianum and placebo. Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C. Gordon A, et al. The Alfred Hospital, Victoria, Australia. J Gastroenterol Hepatol 2006 Jan;21(1 Pt 2):275-80. However, silibinin was effect against hepatitis B hepatoma cells in vitro. Clin Cancer Res 2005 Dec 1;11(23):8441-8.

Obesity Worsens Hep C and Makes Harder to Treat: Obesity and the metabolic syndrome have hepatic manifestations, including steatosis and progression of fibrosis. In individuals with chronic hepatitis C, obesity is associated with inflammation, insulin resistance, steatosis, progression of fibrosis, and nonresponse to treatment with interferon or peginterferon alpha and ribavirin. Patients with both hepatitis C and obesity-related nonalcoholic fatty liver disease are at greater risk for more advanced liver disease. Charlton, et al. Mayo Clinic. Hepatology 2006 Jun;43(6):1177-86.

4% of Americans Developing Hep C: 15,079 participants in the National Health and Nutrition Examination Survey between 1999 and 2002. The prevalence of anti-HCV in the United States was 1.6% or 4.1 million anti-HCV-positive persons nationwide; 1.3% or 3.2 million had chronic HCV infection. Peak prevalence of anti-HCV (4.3%) was ages 40-49. 48.4% of anti-HCV-positive had a history of injection drug use. Other significant risk factors included 20 or more lifetime sex partners and blood transfusion before 1992. Abnormal serum ALT levels were found in 59% of HCV RNA-positive persons. History of injection drug use is the strongest risk factor for infection. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Armstrong GL, et al. CDC. . Ann Intern Med 2006 May 16;144(10):705-14.

Flavastatin may improve response to Peg-Interferon.

Smoking Increases Cirrhosis: Smokers with hep C were 50% more likely to have high hepatic fibrosis scores. Clin Gastroenterol Hep 2006 Jun;4(6):797-801.

Selenium and Zinc Low in Hep C: World J Enterol 2005 Aug 14;11(30):4697-702. and Biol Trace Elem Res 2006 Jan;109(1):15-24 and J Hepatol 2002 Jun;36(6):805-11.  Lipid peroxidation is increased, suggesting melatonin might help. HCC patients have lower selenium levels. Am J Epidem 1999 Aug 15;150(4):367-74.

Vitamins C, E, and Selenium No Impact in Very Small Study: In a 6-month DB PC study of 23 hepatitis C patients, no significant benefit was found. Eur J Gastrolentol Hepatol 2006 Sep;18(9):985-9.