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Highest Rated Articles

Cammà C, Bruno S, Di Marco V et al. Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C. Hepatology. 2006;43:64-71.

Many with HCV, especially those with genotype 3 HCV, high BMI, or fibrosis exhibit hepatic steatosis. The central role of insulin resistance in non-alcoholic fatty liver disease is increasingly recognized. Data are conflicting about whether insulin resistance in the absence of obesity (or other features of metabolic syndrome) are operative in steatosis seen with non- genotype 3 HCV. This prospective study was designed to look at insulin in nondiabetic patients with genotype 1 HCV. The "homeostasis model assessment" (HOMA), one of several validated ways of measuring insulin resistance was used. The 291 evaluable patients did not have diabetes, were all HCV treatment naïve, had elevated ALT levels, and had a liver biopsy performed with the 6 months preceding enrollment. Fewer than 1 in 5 had moderate or severe steatosis. The authors claim that high a HOMA score was associated with steatosis, yet their data provides only the slimmest evidence. Of a statistical relationship that has very limited power. The odds ration, after all, was merely 1.076. Univariate analysis showed a significant relationship between higher HOMA scores and moderate/severe steatosis, but the overlap was substantial. And the logistic regression model to predict moderate/severe steatosis indicates that gender and GGT are 50% - 150% more powerful than HOMA score. Finally HOMA score did not enter into multivariate analysis in predicting fibrosis score. Based on this data HCV infected individuals with compensated liver disease and without features of metabolic syndrome or significant alcohol intake, infrequently have steatosis (20%) which is only weakly associated with insulin resistance as measured by HOMA score. Even more important clinically, insulin resistance in this group is not related to fibrosis.

Raimondo G, Brunetto MR, Pontisso P et al. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-coinfected patients. Hepatology. 2006;43:100-107.

Coinfection with hepatitis B and hepatitis C should come as no surprise, given shared risk factors. HBV/HCV coinfection is most often expressed as a positive anti HCV in the presence of HBsAg. More rapid progression of fibrosis to cirrhosis, and higher rates of development of hepatocellular carcinoma are consequences. Conflicting data from reports about the effect of HCV on HBV, and vice versa defy easy resolution. The current study followed a large group of HBV/HCV co-infected patients (of which 23% were triple-infected [HBV/HDV/HCV]). Considering only cases without evidence of Hepatitis D, the commonest virologic pattenr (seen in 48%) was a relatively low (<10⁵ copies/ml) levels of HBV DNA, and high levels (> 600,000 IU/ml) of HCV RNA, thus confirming previous reports that HCV tends to inhibit HBV replication. However, 24% had active HBV and HCV simultaneously, and significant numbers had high levels of HBV DNA but low levels of HCV RNA. More important, the pattten was not stable over time. It is difficult to know the current clinical relevance of these findings, but they must be taken into account in study designs of treatment for HBV/HCV co-infected patients. At the very least, it seems logical that approaches to antiviral therapy might need to be tailored to the specific profile of the patient, and possibly modified as the profile changes.



Smith M, Walters KA, Korth M et al. Gene expression patterns that correlate with hepatitis C and early progression to fibrosis in liver transplant recipients. Gastroenterology. 2006;130(1):179-187.

These clever investigators chose to study patterns of gene expression from serial liver biopsy specimens in patients who received a liver transplant due to hepatitis C. Control liver biopsy specimens were included. A unique pattern of gene expression indicating up-regulation of stress response proteins and coagulation was seen only in transplant patients (regardless of HCV status). Another pattern of gene expression seen in most HCV infected samples, was absent in the subgroup who developed early fibrosis. If these findings are validated, and particularly if these patterns hold true for the non-transplant HCV infected population, a powerful new tool will become available. Commercial testing kits could be developed to provide clinicians better tools for sorting out which HCV infected patients are and are not at risk for development of progressive liver disease.

Uberti-Foppa C, De Bona A, Galli L et al. Liver fibrosis in HIV-positive patients with hepatitis C virus: role of persistently normal alanine aminotransferase levels. J Acquir Immune Defic Syndr. 2006;41(1):63-67.

This retrospective study extends observations well-known to apply to the HCV mono-infected patient to those with HCV/HIV coinfection. Coinfected patients, like monoinfected patients, are more likely to have less fibrosis on biopsy if their ALT values are persistently normal. Unfortunately, reliance on normal ALT values will underestimate fibrosis in coinfected patients (just as in moninfected patients). The study design in this and most other studies is limited in its power to exclude second liver diseases to account for the fibrosis seen in those with persistently normal liver enzymes. Although the authors excluded heavy alcohol consumption (> 50 gm per day for > 2 years), lesser amounts of alcohol, particularly in women, and in HCV infected patients, may be associated with significant fibrosis. Morevover, the role of obesity, metabolic syndrome as a risk factor for fibrosis was not addressed. Is the glass three-quarters empty, or one-quarter full? The authors" emphasis is on the 25% with normal liver enzymes who had significant fibrosis. The follow up observation of 24 patients with initially normal enzymes reveals that 1/3 lost their favored status and developed elevated transaminases. One developed decompensated cirrhosis, and another died of liver cirrhosis.

de Ledinghen V, Douvin C, Kettaneh A et al. Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr. 2006;41(2):175-179.

The train is coming down the track. The need for liver biopsy to determine the degree of hepatic fibrosis in HCV has been dogma for decades. Its primacy is increasingly challenged by non-invasive means to assess liver fibrosis. It is intuitive that a liver with significant fibrosis will be less supple (stiffer) than one without. Ultrasonographic techniques for acquiring information related to stiffness are available. Termed transient elastography, this technique will become routine in the years to come. This study demonstrates good correlation between the stiffness quotient of livers in those with HIV/HCV coinfection and the degree of fibrosis by biopsy. The test is most useful in distinguishing frank cirrhosis (stage 4 fibrosis) from all other stages. Expect much more literature about this non-invasive test in the months and years to come.

Firpi RJ, Zhu H, Morelli G, Abdelmalek MF et al. Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation. Liver Transpl. 2006;12(1):51-57.

Currently, transplantation of the HCV infected patient is followed almost universally by HCV recurrence. Although the short- term and intermediate term implications of this infection are not great, some develop rapid fibrosis and cirrhosis. It is reasonable to ask what role, if any, specific immunosuppression regimens have on HCV in the liver graft. Moderate success in treating HCV in the liver transplant recipient has been achieved. This retrospective study suggests that SVR was nearly twice as likely to occur in patients receiving cyclosporine, compared to those receiving tacrolimus. Moreover, in vitro studies showed a dose-related inhibition of HCV replicon RNA replication by cyclosporine, but not by tacrolimus. The results of this study is intriguing. Despite the obvious limitation posed by the retrospective nature of the main portion of this study, these observations need to be taken seriously. It is discomforting to view table 2 and the text in the paper; the mortality rate was 23% in cyclosporine-treated patients but only 10% in those receiving tacrolimus (P = 0.05). The authors opine that the reason for the higher death rate was likely related to the longer follow up in the cyclosporine treated group. An actuarial survival calculation would help to determine if this is the case. More and better data are needed.

Clinical Infectious Disease
Rating	Article Title
	Pearlman BL. Hepatitis C virus infection in African Americans. Clin Infect Dis. 2006; Jan 1;42(1):82-91. Epub 2005 Nov 29.
	Verma S, Wang CH, Govindarajan S, Kanel G, Squires K, Bonacini M. Do type and duration of antiretroviral therapy attenuate liver fibrosis in HIV-hepatitis C virus-coinfected patients? Clin Infect Dis. 2006; Jan 15;42(2):262-70. Epub 2005 Dec 2.
	Scott JD, McMahon BJ, Bruden D et al. High rate of spontaneous negativity for hepatitis C virus RNA after establishment of chronic infection in Alaska Natives. Clin Infect Dis. 2006; Apr 1;42(7):945-52. Epub 2006 Feb 28.
	Hagan H, Latka MH, Campbell JV et al. Eligibility for treatment of hepatitis C virus infection among young injection drug users in 3 US cities. Clin Infect Dis. 2006; Mar 1;42(5):669-672. Epub 2006 Jan 20.
	Barreiro P, Martin-Carbonero L, Nunez M et al. Predictors of liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HCV) infection: assessment using transient elastometry and the role of HCV genotype 3. Clin Infect Dis. 2006; Apr 1;42(7):1032-1039. Epub 2006 Feb 21.
European Journal of Gastroenterology and Hepatology
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	Obrador BD, Prades MG, Gomez MV et al. A predictive index for the diagnosis of cirrhosis in hepatitis C based on clinical, laboratory, and ultrasound findings. Eur J Gastroenterol Hepatol. 2006; Jan;18(1):57-62.
	Robaeys G, Van Vlierberghe H, Mathei C, Van Ranst M, Bruckers L, Buntinx F; BASL Steering Committee; Benelux Study Group. Similar compliance and effect of treatment in chronic hepatitis C resulting from intravenous drug use in comparison with other infection causes. Eur J Gastroenterol Hepatol. 2006; Feb;18(2):159-166.
	Condat B, Asselah T, Zanditenas D et al. Fatal cardiomyopathy associated with pegylated interferon/ribavirin in a patient with chronic hepatitis C. Eur J Gastroenterol Hepatol. 2006; Mar;18(3):287-289.
	Tahrani A, Bowler L, Singh P, Coates P. Resolution of diabetes in type 2 diabetic patient treated with IFN-alpha and ribavirin for hepatitis C. Eur J Gastroenterol Hepatol. 2006; Mar; 18(3):291-293.
Gastroenterology
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	Volkov Y, Long A, Freeley M et al. The hepatitis C envelope 2 protein inhibits LFA-1-transduced protein kinase C signaling for T-lymphocyte migration. Gastroenterology. 2006; Feb;130(2):482-492.
Hepatology
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	Iwasaki Y, Ikeda H, Araki Y et al. Limitation of combination therapy of interferon and ribavirin for older patients with chronic hepatitis C. Hepatology. 2006;43:54-63.
	Tarr AW, Owsianka AM, Timms JM et al. Characterization of the hepatitis C virus E2 epitope defined by the broadly neutralizing monoclonal antibody AP33. Hepatology. 2006; Feb 22;43(3):592-601.
	Martínez-Bauer E, Crespo J, Romero-Gómez M et al. Development and validation of two models for early prediction of response to therapy in genotype 1 chronic hepatitis C. Hepatology. 2006;43:72-80.
	Huang Y, Chen XC, Konduri M et al. Mechanistic link between the anti-HCV effect of interferon gamma and control of viral replication by a Ras-MAPK signaling cascade. Hepatology. 2006;43:81-90.
	Umemura T, Wang RY, Schechterly C, Shih JW, Kiyosawa K, Alter HJ. Quantitative analysis of anti-hepatitis C virus antibody-secreting B cells in patients with chronic hepatitis C. Hepatology. 2006;43(1):91-99.
	Feld JJ, Liang TJ. Hepatitis C - identifying patients with progressive liver injury. Hepatology. 2006;43;S194-S206.
	Pawlotsky JM. Therapy of hepatitis C: From empiricism to eradication. Hepatology. 2006;43:S207-S220.
	Patel K, Norris S, Lebeck L et al. HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C. Hepatology. 2006;43:241-249.
	Nahmias Y, Casali M, Barbe L, Berthiaume F, Yarmush ML. Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes. Hepatology. 2006;Feb;43(2):257-265.
	Blasco A, Forns X, Carrion JA et al. Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation. Hepatology. 2006;Feb 22;43(3):492-499.
	Neumann-Haefelin C, McKiernan S, Ward S et al. Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. Hepatology. 2006;43:563-572.
	Morishima C, Paschal DM, Wang CC et al. Decreased NK cell frequency in chronic hepatitis C does not affect ex vivo cytolytic killing. Hepatology. 2006;43:573-580.
	Kennedy PT, Urbani S, Moses RA et al. The influence of T cell cross-reactivity on HCV-peptide specific human T cell response. Hepatology. 2006;43(3):602-611.
	Appel N, Bartenschlager R. A novel function for a micro RNA: Negative regulators can do positive for the hepatitis C virus. Hepatology. 2006;43(3):612-615.
	Evans JD, Seeger C. Cardif: A protein central to innate immunity is inactivated by the HCV NS3 serine protease. Hepatology. 2006;43(3):615-617.
Journal Acquired Immune Deficiency Syndrome
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	Luetkemeyer A, Hare CB, Stansell J et al. Clinical presentation and course of acute hepatitis C infection in HIV-infected patients. J Acquir Immune Defic Syndr. 2006;41(1):31-36.
	Torti C, Lapadula G, Puoti M et al. Influence of genotype 3 hepatitis C coinfection on liver enzyme elevation in HIV-1-positive patients after commencement of a new highly active antiretroviral regimen: results from the EPOKA-MASTER Cohort. J Acquir Immune Defic Syndr. 2006;41:180-185.
Liver Transplantation
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	Watt KD, Lyden ER, Gulizia JM, McCashland TM. Recurrent hepatitis C posttransplant: early preservation injury may predict poor outcome. Liver Transpl. 2006;12(1):134-139.
	Powers KA, Ribeiro RM, Patel K, et al. Kinetics of hepatitis C virus reinfection after liver transplantation. Liver Transpl. 2006;12(2):207-216.
	Kimball P, Baker M, Fisher RA. Allograft TNF beta and IL16 polymorphisms influence HCV recurrence and severity after liver transplantation. Liver Transpl. 2006; Feb;12(2):247-252.
	Golden-Mason L, Rosen HR. Natural killer cells: Primary target for hepatitis C virus immune evasion strategies? Liver Transpl. 2006;12(3):363-372. [Epub ahead of print].