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Highest Rated Articles

Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128:636-41.

Factors associated with a less favorable response to HCV therapy include high viral load, advanced degrees of hepatic fibrosis, genotype 1 or 4 HCV, obesity, and African-American race. This study explores markers of insulin resistance (HOMA-IR) as a marker of resistance to therapy for HCV. The investigators found an inverse correlation between insulin resistance and response to HCV therapy. Moreover, clearance of HCV with treatment was associated with improvement in insulin resistance. It cannot be determined from this study whether or not it is appropriate or useful to add measures of insulin resistance to the clinical evaluation of HCV-infected patients considered for therapy. Further studies are needed to answer this question and the equally intriguing question as to whether treating insulin resistance prior to antiviral therapy will improve response rates to antiviral therapy.

Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, Arakawa Y, Hashimoto E, Hirota K, Yoshida H, Ohashi Y, Omata M; Tokyo-Chiba Hepatitis Research Group. Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival. Ann Intern Med. 2005;142:105-14.

This report indicates that successful treatment of hepatitis C virus (HCV) in those with cirrhosis provides some protective effect from subsequent development of hepatocellular carcinoma (HCC). It joins at least 20 other studies of interferon for prevention of HCC. (See Craxi A, Camma C. Prevention of hepatocellular carcinoma. Clin Liver Dis. 2005;9:329-346). Craxi's meta-analysis of 4,659 patients in 20 controlled clinical trials reveals a marked heterogeneity in the magnitude of the preventive effect of interferon therapy on the risk of HCC. Moreover, the effect of interferon on HCC prevention in pooled data does suggest a slight beneficial effect. The current study is small, and the findings are consistent with Craxi's meta-analysis. Treatment in this group not only conferred an apparently lower risk of HCC; mortality was considerably lower as well.

Fartoux L, Chazouilleres O, Wendum D, Poupon R, Serfaty L. Impact of steatosis on progression of fibrosis in patients with mild hepatitis C. Hepatology. 2005;41:82-7.

The liver with two injuries is more likely to develop fibrosis. Those with HCV with minimal liver disease (eg, normal or near normal ALT values, bland liver biopsies) and no other liver insult (eg, excess alcohol, fatty liver, iron overload) generally do not develop progressive liver disease. This carefully designed study elegantly confirms the specific effect hepatic steatosis has on the evolution of mild HCV. Eighty-four percent of 135 patients with mild HCV at the outset had no progression of fibrosis at a mean follow-up of over 5 years. The minority who developed progressive fibrosis had a much higher degree of hepatic steatosis than those without progression (and were more likely to have genotype 3 HCV). The authors' conclusions are well supported by their data. An individual with significant hepatic steatosis should be considered for antiviral therapy even if the ALT is normal or nearly so, and even if the initial biopsy shows lack of significant fibrosis.

Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, Darriet M, Couzigou P, De Ledinghen V. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-50.

Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48-54.

There continues to be a great deal of interest in methods to determine the extent of fibrosis in patients with liver disease. Liver biopsy remains the most accurate tool, but its many limitations are well chronicled. FibroScan is a vibrator device coupled to an ultrasound system (Echosens, Paris, France) for detection of hepatic fibrosis and cirrhosis. The signal from this device allows a calculation of stiffness of scanned tissue. Two studies of similar design are reported. The devices in each were provided by the manufacturer. Disclosures of potential conflicts of interest are not provided in either report.

In the study by Castera et al, FibroScan in HCV-infected individuals was compared to liver biopsy and to Fibrotest (a proprietary test of liver fibrosis using a number of serologic tests and patient characteristics to predict hepatic fibrosis), singly and in combination.

In both studies, the range of FibroScan values in each stage of fibrosis revealed considerable overlap. Only very high or very low values make it possible to predict the presence or absence of cirrhosis. In the Castera study, agreement between FibroScan and Fibrotest results produced the best predictor of hepatic fibrosis on liver biopsy; however, even here the overlap in values is considerable.

Data presented in these and similar publications advocating the value of noninvasive means of predicting hepatic fibrosis lack clinical clarity. The white blood cell count, platelet count, bilirubin, albumin, presence or absence of cirrhosis, varices, and enlarged spleen in the 25% and 20%, respectively, of patients with cirrhosis in these studies is not presented. The Ziol study excluded those with ascites. Receiver operator characteristics (ROC) curves are statistically interesting but lack clear clinical relevance when presented without reference to other important markers of cirrhosis. Only after excluding patients with "obvious" cirrhosis by these clinical markers can one ascertain the true clinical value of any test to predict cirrhosis. Moreover, important information derived from a liver biopsy goes beyond determination of the degree of fibrosis. An emerging need is accurate assessment of degree of steatosis that has an important impact on the likelihood of progressive liver injury (see below). It is premature to conclude that either FibroScan or Fibrotest are superior in performance to careful selection of patients for liver biopsy in HCV.

Radkowski M, Gallegos-Orozco JF, Jablonska J, et al. Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. Hepatology. 2005;41:106-14.

The end-point of antiviral therapy is a sustained virologic response (SVR)-absence of detectable virus in serum 6 months after cessation of therapy. Such an outcome augurs well for the patient. Follow-up studies for 5 years indicate sustained absence of virus in 98%, with concomitant evidence of histologic improvement and, in many studies, a somewhat lessened risk of liver cancer. However, this study confirms that the HCV-infected patient who achieves SVR still has evidence of HCV in macrophages, lymphocytes, and in the liver for nearly a decade after SVR has been achieved. It seems likely that these reservoirs of HCV are responsible for the 2% to 8% relapse rate seen in SVR achievers. It may also predict relapses of HCV hepatitis in individuals who become immune suppressed in later years due to intercurrent diseases.

Duberg AS, Nordstrom M, Torner A, et al. Non-Hodgkin's lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection. Hepatology. 2005;41:652-9.

It is estimated that more than 170 million people world-wide are infected with HCV. Clearly, all who do not succumb to HCV will develop other medical problems, including non-Hodgkin's lymphoma (NHL) and other malignancies. Therefore, finding many patients with HCV and another disease such as NHL does not imply cause and effect. Only through careful epidemiologic studies can cause and effect be reasonably inferred. This elegant report utilizes a closed medical system in Sweden where the lifetime medical history of nearly all citizens can be mapped. More than 27,000 patients with HCV were studied. An association between HCV and subsequent development of B-cell NHL and multiple myeloma after 15 years of HCV was established. The magnitude of the risk was relatively modest. It is intriguing to speculate on how HCV may promote these malignancies. The presence of HCV in immunologic cells is a tantalizing place to begin.

Mehta SH, Thomas DL, Torbenson M, et al. The effect of antiretroviral therapy on liver disease among adults with HIV and hepatitis C coinfection. Hepatology. 2005;41:123-31.

The interrelationship of HCV, human immunodeficiency virus (HIV), and drugs given to combat each infection is complicated indeed. This study seems to absolve antiretroviral therapy (ART) (which may cause acute liver injury in 5% to 10%) of playing a significant role in the development of hepatic fibrosis or cirrhosis. Just as there was no apparent deleterious effect, there was no beneficial effect on fibrosis scores in those who received ART. On the other hand, less necroinflammation was seen in those who received long-term ART and who had HIV suppression. This study also found a surprisingly high percentage (about 33%) of coinfected patients had no evidence of fibrosis. Although this study is retrospective, it provides encouragement fors the utility and safety of ART in those with HIV/HCV.

American Journal of Gastroenterology
Rating	Article Title
	Zein, Claudia O., Levy, Cynthia, Basu, Ananda, Zein, Nizar N. Chronic Hepatitis C and Type II Diabetes Mellitus: A Prospective Cross-Sectional Study. Am J Gastro. Jan. 2005;100:48-55.
	Kramer JR, Giordano TP, Souchek J, Richardson P, Hwang LY, El-Serag HB. The Effect of HIV Coinfection on the Risk of Cirrhosis and Hepatocellular Carcinoma in U.S. Veterans with Hepatitis C. Am J Gastro. 2005;100:56-63.
	Rulyak SJ, Eng SC, Patel K, McHutchison JG, Gordon SC, Kowdley KV. Relationships between hepatic iron content and virologic response in chronic hepatitis C patients treated with interferon and ribavirin. Am J Gastroenterol. 2005;100:332-7.
	Daniel S. Chronic Hepatitis C Treatment Patterns in African American Patients: An Update. Am J Gastroenterol. 2005;100:716-22.
	Sterling RK, Brown RS Jr, Hofmann CM, et al. The spectrum of chronic hepatitis C virus infection in the Virginia Correctional System: development of a strategy for the evaluation and treatment of inmates with HCV. Am J Gastroenterol. 2005;100:313-21.
	Chapko MK, Sloan KL, Davison JW, et al. Cost Effectiveness of Testing Strategies for Chronic Hepatitis C. Am J Gastroenterol. 2005;100:607-15.
European Journal of Gastroenterology & Hepatology
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	Thomopoulos KC, Theocharis GJ, Tsamantas AC, et al. Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol. 2005;17:149-53.
Gastroenterology
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	Sherman KE, Shire NJ, Rouster SD, et al. Viral kinetics in hepatitis C or hepatitis C/human immunodeficiency virus-infected patients. Gastroenterology. 2005;128:313-27.
	Otani K, Korenaga M, Beard MR, et al. Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells Gastroenterology. 2005;128:96-107.
	Dharancy S, Malapel M, Perlemuter G, et al. Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. Gastroenterology. 2005;128:334-42.
	Marshall A, Rushbrook S, Davies SE, et al. Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection. Gastroenterology. 2005;128:33-42.
	Honda M, Shimazaki T, Kaneko S. La protein is a potent regulator of replication of hepatitis C virus in patients with chronic hepatitis C through internal ribosomal entry site-directed translation. Gastroenterology. 2005;128:449-62.
Hepatology
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	Weston SJ, Leistikow RL, Reddy KR, et al. Reconstitution of hepatitis C virus-specific T-cell-mediated immunity after liver transplantation. Hepatology. 2005;41:72-81.
	Dominitz JA, Boyko EJ, Koepsell TD, et al. Elevated prevalence of hepatitis C infection in users of United States veterans medical centers. Hepatology. 2005;41:88-96.
	Chalasani N, Manzarbeitia C, Ferenci P, et al. Peginterferon alfa-2a for hepatitis C after liver transplantation: Two randomized, controlled trials. Hepatology. 2005;41:289-98.
	Lindahl K, Stahle L, Bruchfeld A, Schvarcz R. High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology. 2005;41:275-9.
	Lavillette D, Tarr AW, Voisset C, et al. Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology. 2005;41:265-74.
	Rousselet MC, Michalak S, Dupre F, et al. Sources of variability in histological scoring of chronic viral hepatitis. Hepatology. 2005;41:257-64.
	Schwegler EE, Cazares L, Steel LF, et al. SELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma. Hepatology. 2005;41:634-42.
	Kamegaya Y, Hiasa Y, Zukerberg L, et al. Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis. Hepatology. 2005;41:660-7.
	Rothman AL, Morishima C, Bonkovsky HL, et al. Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C. Hepatology. 2005;41:617-25.