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5 Highest Rated Articles

Afdhal NH, Dieterich DT, Pockros PJ, et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: A prospective, double-blind, randomized controlled study. Gastroenterology. 2004;126:1302-11.

Hepatitis C affects nearly 3 million in the United States and untold millions around the world. Although many hepatitis C virus (HCV)-infected individuals will live a normal life without dramatic signs or symptoms of infection or of cirrhosis, in approximately 20% advanced liver disease will occur. Many will die from end-stage cirrhosis or from development of hepatocellular carcinoma. Eradication of HCV by antiviral treatment appears to arrest liver disease progression. In some, reversal of fibrosis and even cirrhosis may be seen. Risk of hepatocellular carcinoma is also dramatically reduced.

The goal of antiviral treatment in HCV infection is eradication of measurable virus in the blood. When virus is absent 6 months after treatment is stopped, a sustained virologic response (SVR) has occurred and the patient appears cured. Unfortunately, many who undergo therapy do not achieve SVR status. Multiple factors are associated with a reduced likelihood of SVR, including HCV genotypes 1 or 4, obesity, advanced fibrosis on biopsy, human immunodeficiency virus co-infection, and African genealogy. Another factor influencing the likelihood of an SVR is the ability to take antiviral therapy without dosage reduction.

Unfortunately, dosage reductions are often prompted either by side effects or the effects of medication on hematopoietic cells. Anemia may be produced by interferon, but ribavirin, which produces a hemolytic anemia in many, is most likely to cause significant anemia. When this happens, quality of life suffers, dosage reductions are often necessary, and the result is a lowered chance for SVR. Steps to reduce anemia during treatment of HCV are clearly needed. Administration of erythrocyte stimulating factor is a logical choice to ameliorate the anemia caused by hemolysis. This elegant study by Afdhal et al shows the benefit of administration of epoetin alfa over 8 weeks in a prospective randomized trial of HCV patients treated with interferon and ribavirin. The full dosage of ribavirin was maintained in 88% of those randomized to receive epoetin alfa, compared with 60% in those who were not. This was associated with a much improved quality-of-life score.

Study criteria called for epoetin alfa when the hemoglobin dropped below 12 g/dL. In the routine clinical practice, it would be reasonable to let patient symptoms dictate when to add this expensive support. The impact on hemoglobin correlates with improved quality of life. Not demonstrated (yet) by this study is actual improvement in SVR in those who were treated.

Shiffman ML, Di Bisceglie AM, Lindsay KL, et al. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology. 2004;126:1015-23.

Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346-55.

Pegylated interferon together with ribavirin is the best available treatment for HCV. Ribavirin increases the side-effect profile of treatment, mainly by inducing anemia. Reduction in cost, side effects, and potentially outcome, measured as virus absent from blood 6 months after the end of treatment (ie, a sustained virologic response), is currently the goal of therapy.

Could we get by using lower dosages of ribavirin? This large prospective randomized controlled trial provides the answer. Those with genotype 1 HCV infection who received the standard weight-based dosage of ribavirin (either 1,000 mg or 1,200 mg per day) had a higher SVR than those who received only 800 mg per day. However, for those with genotypes 2 or 3 HCV, there was no difference in outcome with the low dose compared to the standard dose.

Tailoring treatment to the patient and HCV genotype is complex and demanding, but worthwhile. Those with genotypes 2 or 3 HCV can be treated with 24 weeks of pegylated interferon and only 800 mg of ribavirin. This reduced dosage will substantially improve tolerability of treatment.

Camma C, Di Bona D, Schepis F, et al. Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data. Hepatology. 2004;39:333-42.

The goal of antiviral therapy in HCV is sustained elimination of virus from the blood?a sustained virologic response (SVR). This goal, of course, is not identical with what the patient wants, namely, a normal liver. Many large prospective trials demonstrate the superiority of pegylated interferon in establishing SVR. Today, pegylated interferon given with ribavirin is the best antiviral therapy available for HCV.

This meta-analysis from Italy seeks to determine the improvement, if any, that pegylated interferon affords in the histopathology of HCV infection through three randomized prospective trials in which pegylated interferon was compared with non-pegylated interferon. The effect on liver histology was the primary goal of this analysis.

The effect of pegylated interferon is powerful. The mean fibrosis score of paired pre-treatment and post-treatment biopsies shows a significant reduction in fibrosis scores compared with non-pegylated interferon. Not surprisingly, those who achieved SVR were also more likely to have reduction in liver fibrosis. The benefit was seen both in those with and without cirrhosis.

The very good news regarding treatment of HCV continues. Not only can we eliminate the virus, but also the scar within the liver is diminished in those who respond to treatment.

Monto A, Patel K, Bostrom A, et al. Risks of a range of alcohol intake on hepatitis C-related fibrosis. Hepatology. 2004;39:826-34.

Conventional wisdom in the field of hepatitis is that alcohol and viral hepatitis B or hepatitis C simply do not mix. Most hepatologists advise their patients with hepatitis C to stop drinking altogether. This advice is based on a number of studies from the late 1990s, which show a clear association between alcohol intake and the degree of fibrosis on liver biopsy. Cirrhosis is over-represented in HCV-infected individuals who drink. Most of these studies, however, use a rather high intake of alcohol (eg, 40 grams per day) as a threshold for the definition of drinking. Others have used a cumulative lifetime intake of alcohol. Little data exist that critically examine the relationship between hepatic fibrosis and lesser intakes of alcohol.

The study by Monto is a large and well-designed study of patients coming to three large academic centers for liver biopsy for HCV staging. Detailed patient assessments were done, including drinking patterns. Univariate and multivariate analyses were performed to determine which clinical or laboratory features were most associated with degree of fibrosis on liver biopsy.

The results were surprising. Overall, very little effect of alcohol intake on degree of fibrosis was identified. Only the highest amounts (more than 50 grams per day) of alcohol intake were positively associated with fibrosis. On multivariate analysis, age, alanine aminotransferase level, and inflammatory score were associated with fibrosis but not alcohol intake. The results applied equally to men and women with hepatitis C.

There are no criticisms of design of the current study that do not apply equally to other published reports. It is, of course, very difficult to know with precision how much an individual drinks. Even when purposeful concealment is not a factor, alcohol intake is not a constant in most people's lives. Considerable variability over time may be expected, and many simply do not inventory their lives in this way. So, it is possible that this study, which measures people's self-reporting of alcohol intake, was widely off the mark. It seems unlikely, however, that underestimation of alcohol intake is a major influence on these findings. Even those who self-reported a large amount of daily alcohol intake were largely spared from higher fibrosis scores.

What does this mean for our patients with HCV? It seems to this reviewer that the stern warnings we have previously given about the possible dire consequences of even modest alcohol intake now must be tempered. Alcohol abstinence may be the safest course of action, but an occasional drink appears not to harm the liver in those infected with HCV.

American Journal of Gastroenterology
Rating	Article Title
	Sterling RK, Hofmann CM, Luketic VA. Treatment of chronic hepatitis C virus in the virginia department of corrections: can compliance overcome racial differences to response? Am J Gastroenterol. 2004;99:866-72.
	Coverdale SA, Khan MH, Byth K, et al. Effects of interferon treatment response on liver complications of chronic hepatitis C: 9-year follow-up study. Am J Gastroenterol. 2004;99:636-44.
	Hu KQ, Kyulo NL, Lim N, Elhazin B, Hillebrand DJ, Bock T. Clinical significance of elevated alpha-fetoprotein (AFP) in patients with chronic hepatitis C, but not hepatocellular carcinoma. Am J Gastroenterol. 2004;99:860-5.
	Formann E, Stauber R, Denk DM, et al. Sudden hearing loss in patients with chronic hepatitis C treated with pegylated interferon/ribavirin. Am J Gastroenterol. 2004;99:873-7.
Annals of Internal Medicine
Rating	Article Title
	U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: recommendation statement. Ann Intern Med. 2004;140:462-4.
	Chou R, Clark EC, Helfand M; U.S. Preventive Services Task Force. Screening for hepatitis C virus infection: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2004;140:465-79.
	Zeuzem S. Heterogeneous virologic response rates to interferon-based therapy in patients with chronic hepatitis C: who responds less well? Ann Intern Med. 2004;140:370-81.
Gastroenterology
Rating	Article Title
	Pawlotsky JM, Dahari H, Neumann AU, et al. Antiviral action of ribavirin in chronic hepatitis C. Gastroenterology. 2004;126:703-14.
	Shintani Y, Fujie H, Miyoshi H, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology. 2004;126:840-8.
	Disson O, Haouzi D, Desagher S, et al. Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology. 2004;126:859-72.
Hepatology
Rating	Article Title
	Nomura H, Sou S, Tanimoto H, et al. Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial. Hepatology. 2004;39:1213-9.
	Brau N, Rodriguez-Torres M, Prokupek D, et al. Treatment of chronic hepatitis C in HIV/HCV-coinfection with interferon alpha-2b+ full-course vs. 16-week delayed ribavirin. Hepatology. 2004;39:989-98.
	Zickmund S, Hillis SL, Barnett MJ, Ippolito L, LaBrecque DR. Hepatitis C virus-infected patients report communication problems with physicians. Hepatology. 2004;39:999-1007.
	Ducoulombier D, Roque-Afonso AM, Di Liberto G, et al. Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes. Hepatology. 2004;39:817-25.
	Casiraghi MA, De Paschale M, Romano L, et al. Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology. 2004;39:90-6.
	Sud A, Hui JM, Farrell GC, et al. Improved prediction of fibrosis in chronic hepatitis C using measures of insulin resistance in a probability index. Hepatology. 2004;39:1239-47.
	Walsh MJ, Vanags DM, Clouston AD, et al. Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury. Hepatology. 2004;39:1230-8.
	Dalgard O, Egeland A, Skaug K, Vilimas K, Steen T. Health-related quality of life in active injecting drug users with and without chronic hepatitis C virus infection. Hepatology. 2004;39:74-80.
	Helbig KJ, Ruszkiewicz A, Semendric L, Harley HA, McColl SR, Beard MR. Expression of the CXCR3 ligand I-TAC by hepatocytes in chronic hepatitis C and its correlation with hepatic inflammation. Hepatology. 2004;39:1220-9.
	Choi J, Lee KJ, Zheng Y, Yamaga AK, Lai MM, Ou JH. Reactive oxygen species suppress hepatitis C virus RNA replication in human hepatoma cells. Hepatology. 2004;39:81-9.
	McMahon BJ, Hennessy TW, Christensen C, et al. Epidemiology and risk factors for hepatitis C in Alaska Natives. Hepatology. 2004 Feb;39(2):325-32.
	Grattagliano I, Russmann S, Palmieri VO, et al. Low membrane protein sulfhydrils but not G6PD deficiency predict ribavirin-induced hemolysis in hepatitis C. Hepatology. 2004;39:1248-55.
Journal of Acquired Immune Deficiency Syndrome
Rating	Article Title
	For the Hepatitis Resource Network Clinical Trials Group. Daily Versus Thrice-Weekly Interferon Alfa-2b Plus Ribavirin for the Treatment of Chronic Hepatitis C in HIV-Infected Persons: A Multicenter Randomized Controlled Trial. Acquir Immune Defic Syndr. 200;35:464-472.
Liver Transplantation
Rating	Article Title
	Russo MW, Galanko J, Beavers K, Fried MW, Shrestha R. Patient and graft survival in hepatitis C recipients after adult living donor liver transplantation in the United States. Liver Transpl. 2004;10:340-6.
	Casanovas-Taltavull T, Ercilla MG, Gonzalez CP, et al. Long-term immune response after liver transplantation in patients with spontaneous or post-treatment HCV-RNA clearance. Liver Transpl. 2004;10:584-94.
	Neff GW, O'Brien CB, Cirocco R, et al. Prediction of sustained virological response in liver transplant recipients with recurrent hepatitis C virus following combination pegylated interferon alfa-2b and ribavirin therapy using tissue hepatitis C virus reverse transcriptase polymerase chain reaction testing. Liver Transpl. 2004;10:595-8.
	Zekry A, Gleeson M, Guney S, McCaughan GW. A prospective cross-over study comparing the effect of mycophenolate versus azathioprine on allograft function and viral load in liver transplant recipients with recurrent chronic HCV infection. Liver Transpl. 2004;10:52-7.
	Khalili M, Lim JW, Bass N, Ascher NL, Roberts JP, Terrault NA. New onset diabetes mellitus after liver transplantation: the critical role of hepatitis C infection. Liver Transpl. 2004;10:349-55.
	Mas VR, Maluf DG, Stravitz R, et al. Hepatocellular carcinoma in HCV-infected patients awaiting liver transplantation: genes involved in tumor progression. Liver Transpl. 2004;10:607-20.
	Machicao VI, Krishna M, Bonatti H, et al. Hepatitis C recurrence is not associated with allograft steatosis within the first year after liver transplantation. Liver Transpl. 2004;10:599-606.