Hepatitis: Younossi ZM

Younossi ZM. · No affiliation provided · Cleve Clin J Med. · Pubmed #11068358 No free full text.

This publication has no abstract.

Baranova A, Younossi ZM. · No affiliation provided · Hepatology. · Pubmed #18220279 No free full text.

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Younossi ZM, McCullough AJ. · Inova Fairfax Hospital, Falls Church, VA, USA. · Liver Int. · Pubmed #19187068 No free full text.

Abstract: Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disease ranging from simple steatosis to non-alcoholic steatohepatitis, is increasingly recognized as the hepatic manifestation of metabolic syndrome and is an important cause of liver-related morbidity and mortality. It is among the most common forms of liver disease. NAFLD reflects abnormal partitioning of fat, such that fat deposition is increased in the liver, and provides a link between NAFLD and the metabolic syndrome, a constellation of metabolic disorders that can also be associated with visceral fat or central adiposity. Together, the features of the metabolic syndrome presage overt diabetes and increase cardiovascular risk. Hepatitis C virus (HCV) appears to exacerbate the metabolic syndrome by eliciting increased insulin resistance (IR) and promoting truncal obesity. Moreover, the concomitant presence of HCV and NAFLD is associated with an increased likelihood of diabetes, hypertension and/or hypertriglyceridaemia. Metabolic abnormalities have been shown to influence response to treatment such that the presence of IR or obesity reduces the likelihood of a sustained virological response (SVR); conversely, SVR has been demonstrated to ameliorate IR and improve beta-cell function. Clinically, these data suggest that attention must be paid not only to optimizing antiviral response but also to screening for and treatment of the various components of the metabolic syndrome.

Rafiq N, Younossi ZM. · Center for Liver Diseases at Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072356 No free full text.

Abstract: Nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent liver diseases in the Western world. NAFLD represents a wide spectrum of histologic subgroups, with nonalcoholic steatohepatitis as the most aggressive form. The risk of developing NAFLD is strongly associated with metabolic syndrome and insulin resistance. The pathogenesis of NAFLD is a multiple-hit process resulting from hepatic fat deposition that is related to several conditions, including insulin resistance and central obesity. Additional hits, such as oxidative stress or adipocytokines produced by white adipose tissue, can further enhance liver damage leading to nonalcoholic steatohepatitis or fibrosis. Although NAFLD is often the primary liver disease of metabolic conditions, it can also exacerbate other liver diseases such as hepatitis C (HCV); indeed, more than 50% of patients with HCV have hepatic steatosis. Hepatic steatosis can be related to host factors (e.g., obesity, metabolic syndrome or insulin resistance) or to the genotype of virus (e.g., HCV genotype 3). Increasing evidence suggests that hepatic steatosis, insulin resistance and obesity in the setting of HCV have a negative impact on the efficacy of treatment and hepatic progression of fibrosis.

Rafiq N, Younossi ZM. · Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia 22042, USA. · Semin Liver Dis. · Pubmed #18956298 No free full text.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases worldwide, affecting men, women, and children. This is due, in part, to the obesity epidemic, which is associated with increased prevalence of NAFLD. The NAFLD spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which is the potentially progressive form. NAFLD is associated with metabolic syndrome and insulin resistance. Treatment recommendations include weight reduction through both diet and physical activity, and weight-loss surgery for extreme obesity. Most medical regimens target components of the metabolic syndrome or oxidative stress associated with the pathogenesis of NASH. These include antiobesity regimens, insulin sensitizers, antihyperlipidemics, and antioxidants. Bariatric surgery is effective for achieving and maintaining weight loss and reversing the complications of metabolic syndrome. On the other hand, the literature lacks well-designed, randomized control trials that assess the efficacy of anti-obesity regimens on histologic and long-term outcomes of NAFLD.

Bondini S, Kleiner DE, Goodman ZD, Gramlich T, Younossi ZM. · Center for Liver Diseases at Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA. · Clin Liver Dis. · Pubmed #17544969 No free full text.

Abstract: Non-alcoholic fatty liver disease (NAFLD) represents one of the most common forms of liver disease and is considered the hepatic manifestation of the metabolic syndrome. Within the NAFLD spectrum, simple steatosis is considered benign, whereas non-alcoholic steatohepatitis (NASH) may progress to cirrhosis. The distinction can be made only by liver biopsy. There is not complete agreement on criteria for diagnosis or the features used for grading and staging lesions. This article reviews some of the studies dealing with the histopathology of NAFLD, with attempts to develop a standardized pathologic scoring system for NASH.

Ong JP, Younossi ZM. · Center for Liver Diseases, Inova Fairfax Hospital, 3289 Woodburn Road, Annadale, VA 22003, USA. · Clin Liver Dis. · Pubmed #17544968 No free full text.

Abstract: Understanding of the epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) has increased; it is the most common form of chronic liver disease in the Western world and increasing in importance in other parts of the world. Prevalence is expected to increase as obesity and diabetes epidemics evolve. The natural history of NAFLD depends on the histologic subtype. Those who have simple hepatic steatosis or nonspecific inflammation generally have a benign long-term prognosis, whereas non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. NASH-related cirrhosis may have a similar prognosis as cirrhosis from other causes, leading to liver failure or hepatocellular carcinoma.

Bondini S, Younossi ZM. · Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia 22042, USA. · Minerva Gastroenterol Dietol. · Pubmed #16557185 No free full text.

Abstract: Non-alcoholic fatty liver disease (NAFLD) is now recognized as one of the most important causes of chronic liver disease in Western Countries, and is the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD has increased with the global epidemic of obesity and type 2 diabetes mellitus. The pathophysiological hallmark of NAFLD is insulin resistance, associated with mediators of oxidative stress and inflammatory cytokines. Although simple steatosis by itself is generally benign, patients with histologically proven non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. Hepatitis C (HCV) is another common cause of liver disease with some potential for progression to cirrhosis. Steatosis is present in almost 50% of patients infected by HCV. Hepatic steatosis in the setting of another liver disease (such as HCV) is associated liver disease progression. In particular, significant fibrosis is observed in patients with HCV whose liver biopsies show significant steatosis or superimposed NASH. This article reviews the host and viral factors potentially involved in the interaction between NAFLD and HCV. These factors include mediators of metabolic syndrome such as adipokines, inflammatory cytokines, factors associated with oxidative stress, lipid peroxidation products, as well as apoptosis and hepatic stellate cell activation with the resultant deposition of extracellular matrix. In addition to the mediators of metabolic syndrome (host factors), hepatic steatosis can be influenced by viral factors. The most important viral factor is HCV genotype 3, which has been independently associated with hepatic steatosis. Finally, superimposed NAFLD and visceral fat are associated with lower response rates to antiviral therapy in non-genotype 3 patients. Furthermore, viral clearance is associated with the resolution of hepatic steatosis in HCV genotype 3 but not other HCV genotypes. In these genotypes, hepatic steatosis and its impact on response to therapy are related to metabolic syndrome. Thus, the management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression as well as improving the efficacy of antiviral therapy.

Spiegel BM, Younossi ZM, Hays RD, Revicki D, Robbins S, Kanwal F. · Division of Gastroenterology, VA Greater Los Angeles Healthcare System, USA. · Hepatology. · Pubmed #15791608 No free full text.

Abstract: Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF-36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel concluded that the SF-36 vitality scale was most relevant in patients with HCV, and generated a mean MCID of 4.2 points on this scale. In conclusion, patients with HCV have a clinically significant decrement in HRQOL versus controls, and physical HRQOL improves in patients achieving SVR but not in those without SVR. The data further suggest that traditional outcomes fail to capture the full spectrum of illness related to chronic HCV. A difference of 4.2 points on the SF-36 vitality scale can be used as an estimate of the MCID in HCV, and this value may be used as the basis for power calculations in clinical trials evaluating HRQOL. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Collantes RS, Younossi ZM. · Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, VA 22042, USA. · J Clin Gastroenterol. · Pubmed #15597026 No free full text.

Abstract: Hematologic side effects (anemia, neutropenia, and thrombocytopenia) of combination therapy with pegylated (PEG)-interferon alfa and ribavirin are commonly encountered during antiviral therapy for chronic hepatitis C (HCV). An important consequence of these side effects is dose modification of PEG-interferon alfa, ribavirin, or both. Dose modification (including discontinuation) diminishes the efficacy of optimal treatment regimen for HCV and may have a negative impact on sustained virologic response. Additionally, fatigue associated with anemia may impair patients' quality of life. The clinical implications of neutropenia or thrombocytopenia are less clear than for anemia; nevertheless, severe infection and bleeding are uncommon. Dose adjustments effectively treat these hematologic side effects, but the resulting suboptimal dosing and potential impact on virologic response are major concerns. Recent attempts to maximize adherence to the optimal treatment regimen have used hematopoietic growth factors rather than dose adjustment to treat side effects. Research on growth factor support has focused on anemia and neutropenia. Epoetin alfa and darbepoetin alfa are erythropoietic growth factors that effectively increase hemoglobin while maintaining the optimal ribavirin dose and improving patients' quality of life. Preliminary work suggests that filgrastim, granulocyte colony stimulating factors, may be an effective treatment of interferon-induced neutropenia. Although this early work shows tremendous promise for managing hematologic side effects of combination therapy for HCV, and potentially enhancing adherence, further research is needed to clarify the efficacy, safety, and cost-effectiveness of growth factors in the management of patients with chronic HCV.

Ong JP, Younossi ZM. · Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA. · Cleve Clin J Med. · Pubmed #15468613 links to  free full text

Abstract: Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common cause of dose reduction or discontinuation. Bone marrow suppression also contributes to the anemia and is the predominant mechanism for interferon-induced neutropenia and thrombocytopenia. Although dose reduction or discontinuation of combination therapy can reverse these abnormalities, they may reduce virologic response. Hematopoietic growth factors may provide a useful alternative for managing these hematologic side effects without reducing the optimal dose of the combination antiviral regimen. Treatment of anemia also may improve patients' health-related quality of life and their adherence to combination antiviral therapy. The impact of growth factors on sustained virologic response and their cost-effectiveness in patients with chronic hepatitis C need further assessment.

Siatkosky LL, Shermock KM, Younossi ZM. · Department of Pharmacy, Spectrum Health, Grand Rapids, MI, USA. · Expert Opin Investig Drugs. · Pubmed #12225249 No free full text.

Abstract: Liver disease can cause significant morbidity and mortality. Few pharmacological options exist for these diseases, however, new agents are in development and older agents are being evaluated for new indications. Several new nucleoside and nucleotide analogues are being developed to treat hepatitis B virus infection. Pegylated interferons have been developed for hepatitis C infection. Ursodeoxycholic acid has recently been implicated in the treatment of liver disease, including non-alcoholic steatohepatitis and primary sclerosing cholangitis.

Younossi ZM, Diehl AM, Ong JP. · Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA 22042, USA. · Hepatology. · Pubmed #11915019 No free full text.

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Younossi ZM, Temple ME, Shermock KM. · I.H. Page Center for Health Outcomes Research & Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042-3300, USA. · Expert Opin Pharmacother. · Pubmed #11336580 No free full text.

Abstract: In the recent years, advances in the treatment of chronic hepatitis B and C have shown that newer, more expensive therapy may result in higher sustained viral response rates. In light of this, the pertinent question for healthcare decision-makers centres around whether this increase in efficacy 'justifies' the additional cost. Pharmacoeconomics is dedicated to helping answer these types of questions. In this article, we will discuss the clinical aspects of hepatitis B and C, recent advances in treatment and studies of the cost-effectiveness of these treatments.

Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. · Schwartz Center for Metabolism and Nutrition, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA. · Semin Liver Dis. · Pubmed #11296693 No free full text.

Abstract: Nonalcoholic steatohepatitis, along with other forms of nonalcoholic fatty liver disease, is a chronic liver disease that is attracting increasing significance. It is a clinicopathologic syndrome that was originally described in obese, diabetic females who denied alcohol use but in whom the hepatic histology was consistent with alcoholic hepatitis. This typical patient profile has been expanded and is now recognized to occur even in normal weight males without overt abnormalities in carbohydrate metabolism. Although originally believed to be a benign clinical entity, nonalcoholic steatohepatitis is now recognized as a cause of progressive fibrotic liver disease with adverse clinical sequelae. It is important to emphasize that nonalcoholic steatohepatitis is best considered one type of a larger spectrum of nonalcoholic fatty liver disease that is a consequence of insulin resistance and ranges from fat alone to fat plus inflammation, fat plus ballooning degeneration, and nonalcoholic steatohepatitis, the latter being the most serious form. As with any disease, the clinical importance of nonalcoholic steatohepatitis is related to its prevalence and natural history. Recent studies using different methodologies indicate that in the general population the prevalence of fatty liver and nonalcoholic steatohepatitis is approximately 20% and 3%, respectively. These prevalence rates are increased in certain subpopulations such as obesity and type II diabetes. Of greater concern is the recognition that cirrhosis and liver-related deaths occur in approximately 20% and 8% of these patients, respectively, over a 10-year period. Risk factors for these adverse clinical symptoms include patients older than the age of 45, the presence of diabetes or obesity, an aspartate aminotransferase/alanine aminotransferase ratio > 1 and hepatic histology. However, a number of important unresolved issues must be clarified before the true natural history of this disease can be fully understood.

Younossi ZM. · The Cleveland Clinic Foundation, Department of Gastroenterology, Desk S-40, 9500 Euclid Avenue, Cleveland, OH 44195, USA. · Curr Gastroenterol Rep. · Pubmed #10980928 No free full text.

Abstract: The definition of nonalcoholic fatty liver disease has evolved in recent years. Today, it is considered a nonspecific term encompassing several clinicopathologic entities (steatosis alone, steatonecrosis, steatohepatitis and histologic alcoholic-like hepatitis) that are similar to alcoholic liver disease. Studies of nonalcoholic fatty liver disease have come to conflicting conclusions about the course of the disease. It can be argued that the disparate results are largely the result of nonuniform definitions. When histologic features such as hepatocyte ballooning, necrosis, and Mallory hyaline are seen, nonalcoholic fatty liver disease has been shown to be associated with an aggressive outcome. Steatosis alone, in contrast, appears to be benign. The current understanding of nonalcoholic fatty liver disease, the limited treatments available, and two theories of the pathogenesis of the disease are also reviewed here.

Zdilar D, Franco-Bronson K, Buchler N, Locala JA, Younossi ZM. · Department of Psychiatry and Psychology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. · Hepatology. · Pubmed #10827143 No free full text.

This publication has no abstract.

Sarbah SA, Younossi ZM. · Metrohealth Medical Center, Cleveland, Ohio, USA. · J Clin Gastroenterol. · Pubmed #10730918 No free full text.

Abstract: Hepatitis C virus (HCV) currently infects an estimated 2-3 million people in the United States and 175 million people globally. Over 80% of infected patients go on to develop chronic disease. Most patients remain asymptomatic despite silent, insidious progression of the disease. The sequelae of HCV-induced chronic liver disease accounts for 8,000-10,000 deaths annually in the United States and is currently the leading indication for liver transplantation. The cost of this epidemic to the United States was estimated in 1991 at $600 million in terms of medical expenses (excluding costs related to liver transplantation) and work lost. Over the last decade, since the viral genome of HCV was first sequenced in 1989, there has been a great increase in understanding of this infection. This review summarizes current knowledge about the hepatitis C epidemic with particular reference to epidemiology of infection, viral characteristics, risk factors for disease, diagnostic testing, clinical manifestations, and current, as well as potential, therapeutic options.

Younossi ZM, Perrillo RP. · Department of Gastroenterology, Cleveland Clinic Foundation, Ohio 44195, USA. · Semin Liver Dis. · Pubmed #10349697 No free full text.

Abstract: Although alpha interferons are currently the standard treatments for chronic hepatitis C, they are effective in only 15% to 20% of patients. This low success rate has prompted research into new approaches for maximizing responses to alpha interferons. A variety of drugs have been investigated alone or in combination with alpha interferons. Of these agents, ribavirin is currently the most promising adjuvant, and the combination therapy of ribavirin plus recombinant interferon alfa-2b is reviewed in detail elsewhere in this issue (see Davis article, pp. 49-55; and McHutchison article, pp. 57-65). This article reviews the literature concerning studies of amantadine, rimantadine, ursodeoxycholic acid (UDCA), and nonsteroidal anti-inflammatory drugs (NSAIDs), which are the most commonly used alternatives to ribavirin. As of this writing, virologic response rates have been unsatisfactory when these agents are used as monotherapies. Furthermore, combining alpha interferons with either UDCA or NSAIDs does not appear to improve sustained virologic response rates. However, combination regimens composed of an alpha interferon plus amantadine, or an alpha interferon plus rimantadine, or triple therapy with either amantadine or rimantadine plus an alpha interferon and ribavirin, warrant further investigation.

Younossi ZM, Nader FH, Bai C, Sjogren R, Ong JP, Collantes R, Sjogren M, Farmer D, Ramsey L, Terra K, Gujral H, Gurung C, Srishord M, Fang Y. · Center for Liver Diseases, Inova Fairfax Hospital, Annandale, VA 22003-6800, USA. · J Viral Hepat. · Pubmed #18194172 No free full text.

Abstract: Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors. This phase II clinical trial assesses the dose, efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus (HCV). Chronic hepatitis C patients (n = 101) received pegylated interferon alpha-2b (1.5 mug/kg once weekly) and ribavirin (800-1400 mg once daily). Patients with anaemia [haemoglobin (Hb) </= 10.5 g/dL] received darbepoetin alpha (3 mug/kg once every 2 weeks); the dose was titrated to achieve a Hb level of 12.0 g/dL. Patients with neutropenia [absolute neutrophil count (ANC) </= 0.75 x 10(9)/L] received filgrastim with the dose titrated from 150 mug QW to 300 mug thrice weekly to maintain ANC >/= 0.75 x 10(9)/L and <10 x 10(9)/L. During antiviral therapy, 52% of patients required darbepoetin alpha, filgrastim or both. Hb at the time of darbepoetin alpha initiation was 10.2 +/- 0.4 g/dL. After 81 days of darbepoetin alpha, Hb increased by 1.9 +/- 1.0 g/dL to 12.1 +/- 1.1 g/dL (P < 0.0001). Filgrastim resulted in a significant increase in ANC [0.75 +/- 0.16 x 109/L to 8.28 +/- 5.67 x 10(9)/L (P < 0.0001)]. In treatment-naïve patients, 48% achieved sustained virological response (SVR), whereas 27% of patients previously treated with a course of pegylated interferon alpha achieved SVR. Low viral load, nongenotype 1 and treatment with growth factors were independently associated with SVR. Mild and severe anaemia were associated with quality of life impairments. Darbepoetin alpha resulted in an improvement in the Vitality domain of Short Form-36. No significant adverse events were related to growth factors. During anti-HCV therapy, filgrastim improved neutropenia and darbepoetin alpha improved both anaemia and quality of life. Future randomized clinical trials are needed to establish the impact of growth factors in improving sustained virological response.

Dan AA, Crone C, Wise TN, Martin LM, Ramsey L, Magee S, Sjogren R, Ong JP, Younossi ZM. · Center for Liver Diseases, DepT. of Psychiatry, Inova Fairfax Hospital, Annandale, VA 22003-6800, USA. · Psychosomatics. · Pubmed #17478591 links to  free full text

Abstract: The authors examined anger among hepatitis C (HCV) patients and its relationship to health-related quality of life (HRQL) and depression. Eighty-seven HCV patients who received pegylated interferon-alpha(2b) and ribavirin were included. Patients' mean age was 48 years; 42% were women, and 60% were white. Patients experienced moderate anger while undergoing HCV treatment. Angry feelings increased during treatment in some domains, specifically, Control Over Anger and Angry Reaction. Greater anger was associated with more depression and poorer HRQL. Findings point to the importance for physicians to screen for a wide range of neuropsychiatric side effects of interferon, including anger.

Younossi ZM, McCullough AC, Barnes DS, Post A, Ong JP, O'Shea R, Martin LM, Bringman D, Farmer D, Levinthal G, Mullen KD, Carey WD, Tavill AS, Ferguson R, Gramlich T. · Inova Fairfax Hospital, Center for Liver Diseases, Department of Medicine, Falls Church, Virginia 22042, USA. · Dig Dis Sci. · Pubmed #15906777 No free full text.

Abstract: In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon alpha-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed. In this open-label pilot study, two separate patient populations with chronic hepatitis C and viremia were enrolled: treatment-naive and those who had failed a previous course of treatment. Patients were started on pegylated interferon alpha-2b at a dose of 1.5 microg/kg weekly with ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for 4 weeks, followed by pegylated interferon alpha-2b, 0.5 microg/kg weekly, ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for another 20 weeks. Patients with undetectable HCV RNA at week 24 continued this regimen for a total of 48 weeks and were followed for another 24 weeks. Patients with undetectable virus (<50 IU/mL) after 24 weeks of follow-up were considered to have SVR. Health-related quality of life and safety data were also collected. Sixty-nine treatment-naive and 99 nonresponder patients with chronic hepatitis C were enrolled in the study. Of all patients enrolled, 74% were male, aged 47.27+/-5.76 years; their body mass index (BMI) was 28.87+/-5.05 kg/m2, 79.4% were white, 85% had HCV genotypes 1 and 4, and 36% had cirrhosis. Their baseline HCV RNA was 689,242+/-698,030 IU/mL, with a baseline ALT of 107.25+/-79.08. Of the entire cohort, 35 (21%) discontinued early due to side effects or loss to follow-up. Significant anemia (hemoglobin, < 10 g/dL) occurred in 11% (19/168), while severe anemia (hemoglobin, <8.5 g/dL) occurred in 0.6% (1/168). In the treatment-naive group, sustained virologic response (SVR) was 34.3%, versus 19.4% for the group who had previously failed to respond to a course of treatment (P = 0.01). For both groups combined, virologic response after 24 weeks of therapy was 40.5%, with an end-of-treatment virologic response of 35.7% and a SVR of 26.2%. Patients with genotypes 1 and 4 had lower response rates than those with genotypes 2 and 3 (SVR, 21 vs. 46%; P = 0.001). Patients with advanced fibrosis (Metavir stages 3 and 4) tended to have lower response rates than those with minimal or mild fibrosis (Metavir stages 0-2) (SVR, 10 vs. 30%; P = 0.08). African-American patients with HCV had lower response rates than Caucasians or other ethnic groups (SVR, 4 vs. 29 vs. 20%; P = 0.04). Age, gender, and BMI did not affect SVR. The addition of amantadine to pegylated interferon alpha-2b and ribavirin does not seem to increase the efficicacy of this regimen.

Younossi ZM, Mullen KD, Zakko W, Hodnick S, Brand E, Barnes DS, Carey WD, McCullough AC, Easley K, Boparai N, Gramlich T. · Department of Gastroenterology, Biostatistics and Anatomic Pathology, the Cleveland Clinic Foundation, OH, USA. · J Hepatol. · Pubmed #11211889 No free full text.

Abstract: BACKGROUND/AIMS: Interferon-based regimens (alone or with ribavairin) are standard therapies for chronic hepatitis C. The aim of this study was to compare a 24-week regimen of interferon alpha-2b + ribavirin (IFN + RIBA) to interferon alpha-2b + amantadine (IFN + AMANT) in non-responders to previous interferon monotherapy. METHODS: In a multi-center, double-blind clinical trial, 118 patients (non-responders to previous interferon monotherapy) were equally randomized into the two arms: interferon alpha-2b (3 MU thrice weekly) and ribavirin (800 mg daily) vs. interferon alpha-2b (3 MU thrice weekly) and amantadine (200 mg daily). RESULTS: After 24 weeks of therapy, HCV RNA became undetectable in 34.8% (95% CI: 23.7-49.2) of IFN + RIBA and 19.6% (95% CI: 10.6-34.7) of IFN + AMANT (P = 0.10). This response was sustained in 3.9% (95% CI: 1.0-14.9) of IFN + RIBA and 0% of IFN + AMANT (P = 0.16). Ten patients from IFN + AMANT (17%) and 12 patients (20%) from IFN + RIBA were discontinued before completion of therapy. Of these, 7% in IFN + AMANT and 12% in IFN + RIBA were discontinued due to adverse effects. CONCLUSIONS: Re-treatment of interferon non-responders with a 24-week course of IFN + AMANT was not associated with any sustained viral eradication. Although IFN + RIBA in this group was associated with a reasonable end of treatment response, relapses were common and sustained responses were low.

Kallman JB, Arsalla A, Park V, Dhungel S, Bhatia P, Haddad D, Wheeler A, Younossi ZM. · Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Rd, Falls Church, VA 22042, USA. · Aliment Pharmacol Ther. · Pubmed #19220207 No free full text.

Abstract: BACKGROUND: Screening guidelines for hepatitis B (HBV) and hepatitis C viruses (HCV) as well as a position statement for non-alcoholic fatty liver disease (NAFLD) have been put forth by different sources, but awareness of these guidelines and their impact on the physician practices have not been assessed. AIM: To assess the attitudes of primary care physicians (PCPs), gastroenterologists (GEs) and hepatologists (HEPs) regarding screening for HBV, HCV and NAFLD. DESIGN: A survey questionnaire was sent to community-based PCPs and GEs to assess issues related to HBV, HCV and NAFLD. The same questionnaire was sent to hepatologists (HEPs). The questionnaire contained 10 items related to demographic and practice patterns of these physicians, 35 items related to HBV, 35 items related to HCV and 29 items related to NAFLD. RESULTS: A total of 214 physicians (103 PCPs, 59 GEs and 52 HEPs) completed the survey. A majority of PCPs, GEs and HEPs agreed on most screening issues for these causes of liver disease. Nevertheless, within group comparison of physicians (guideline aware versus guideline unaware) showed significant differences in accurate response between those who were aware of guidelines and those who were not aware. CONCLUSIONS: A large percentage of PCPs and GEs were unaware of official guidelines for viral hepatitis B and hepatitis C. Those aware of guidelines were more likely to screen appropriately and avoid unnecessary testing. More needs to be done to assess awareness and the impact implementation of guidelines in hepatology.

Younossi ZM, Baranova A, Afendy A, Collantes R, Stepanova M, Manyam G, Bakshi A, Sigua CL, Chan JP, Iverson AA, Santini CD, Chang SY. · Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, VA 22042, USA. · Hepatology. · Pubmed #19140155 No free full text.

Abstract: Responsiveness to hepatitis C virus (HCV) therapy depends on viral and host factors. Our aim was to assess sustained virologic response (SVR)-associated early gene expression in patients with HCV receiving pegylated interferon-alpha2a (PEG-IFN-alpha2a) or PEG-IFN-alpha2b and ribavirin with the duration based on genotypes. Blood samples were collected into PAXgene tubes prior to treatment as well as 1, 7, 28, and 56 days after treatment. From the peripheral blood cells, total RNA was extracted, quantified, and used for one-step reverse transcription polymerase chain reaction to profile 154 messenger RNAs. Expression levels of messenger RNAs were normalized with six "housekeeping" genes and a reference RNA. Multiple regression and stepwise selection were performed to assess differences in gene expression at different time points, and predictive performance was evaluated for each model. A total of 68 patients were enrolled in the study and treated with combination therapy. The results of gene expression showed that SVR could be predicted by the gene expression of signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signaling-1 in the pretreatment samples. After 24 hours, SVR was predicted by the expression of interferon-dependent genes, and this dependence continued to be prominent throughout the treatment. Conclusion: Early gene expression during anti-HCV therapy may elucidate important molecular pathways that may be influencing the probability of achieving virologic response.