Hepatitis: McCullough AJ

McCullough AJ. · No affiliation provided · N Engl J Med. · Pubmed #17135591 No free full text.

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O'Shea R, McCullough AJ. · No affiliation provided · J Hepatol. · Pubmed #16503078 No free full text.

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McCullough AJ. · No affiliation provided · Hepatology. · Pubmed #12939581 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.

Edmison J, McCullough AJ. · Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA. · Clin Liver Dis. · Pubmed #17544973 No free full text.

Abstract: Non-alcoholic fatty liver disease (NAFLD) has moved rapidly to the forefront of clinical disease, with a prevalence of 30% in the adult United States population and a definite but yet uncertain rate of progression to cirrhosis and end-stage liver disease. This disease has an impact on all areas of clinical medicine, with increasing prevalence and adversity. It is essential to understand the pathophysiologic mechanisms involved in NAFLD, so that therapeutic strategies can be developed. Although fatty liver may be caused by other factors, this review concentrates on fatty liver associated with insulin resistance, sometimes referred to as the primary form.

O'Shea RS, McCullough AJ. · Department of Gastroenterology and Hepatology A30, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. · Clin Liver Dis. · Pubmed #15763232 No free full text.

Abstract: Cirrhosis and its sequelae are responsible for close to 2% of all causes of death in the United States. Some studies have suggested that the costs of liver disease may account for as much as 1% of all health care spending, with alcohol-related liver disease (ALD) representing a major portion. It accounts for between 40% to 50% of all deaths due to cirrhosis, with an accompanying rate of progression of up to 60% in patients with pure alcoholic fatty liver over 10 years, and a 5-year survival rate as low as 35% if patients continue to drink. A subset of patients with ALD will develop an acute, virulent form of injury, acute alcoholic hepatitis, which has a substantially worse prognosis. Despite enormous progress in understanding the physiology of this disease, much remains unknown, and therefore, a consensus regarding effective therapy for ALD is lacking. Conventional therapy is still based largely on abstinence from alcohol, as well as general supportive and symptomatic care. Unfortunately, hepatocellular damage may progress despite these measures. Multiple treatment interventions for both the short- and long-term morbidity and mortality of this disease have been proposed, but strong disagreement exists among experts regarding the value of any of the proposed specific therapeutic interventions.

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.

Hanouneh IA, Feldstein AE, McCullough AJ, Miller C, Aucejo F, Yerian L, Lopez R, Zein NN. · Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. · Liver Transpl. · Pubmed #18756451 No free full text.

Abstract: Although hyperinsulinemia and its associated metabolic syndrome (MS) have been implicated in the progression of hepatic fibrosis in hepatitis C virus (HCV) patients, little is known about the consequences of MS after orthotopic liver transplantation (OLT). The aim of this study was to assess the association between MS and fibrosis progression in patients with recurrent HCV after OLT. We identified all OLT/HCV patients (1998-2005) with at least 2 post-OLT liver biopsies. MS was defined with Adult Treatment Panel III criteria at 1 year post-OLT. The Ludwig-Batts scoring system was used to stage all biopsies (408 biopsies from 95 patients). The first biopsy that showed progression post-OLT was used for the time-to-progression analysis. Univariable and multivariable logistic regression analysis was performed to identify factors associated with fibrosis progression. MS was present in 50% of patients. Average follow-up to last available biopsy was 24 +/- 17 months, during which 72% of subjects had fibrosis progression. The overall median rate of fibrosis progression was 0.08 units per month (Q25, Q75: 0.0, 0.17). By univariable analysis, high HCV RNA at 4 months post-OLT (P < 0.001), diabetes (P = 0.046), cytomegalovirus infection (P = 0.006), and MS (P = 0.049) were associated with progression of fibrosis. In multivariable analysis, MS was independently associated with progression of fibrosis beyond 1 year after OLT (odds ratio = 6.3, P = 0.017). A high viral load at 4 months post-OLT (odds ratio = 1.1, P = 0.004) and steroid therapy for acute rejection (odds ratio = 1.9, P = 0.05) were independently associated with fibrosis progression. In conclusion, MS, a potentially modifiable disease, is common and is strongly associated with long-term fibrosis progression in the setting of recurrent HCV after OLT.

Younossi ZM, McCullough AJ, Ong JP, Barnes DS, Post A, Tavill A, Bringman D, Martin LM, Assmann J, Gramlich T, Mullen KD, O'Shea R, Carey WD, Ferguson R. · Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, Virginia 22042, USA. · J Clin Gastroenterol. · Pubmed #15319656 No free full text.

Abstract: BACKGROUND: Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C. METHODS: One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients' baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. < or =33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. RESULTS: Seventy percent of patients were men and 80% were white. The mean age was 47.48+/-5.70 years, mean BMI was 29.01 +/-5.01 kg/m, and mean waist to hip ratio (W/H) was 0.90+/-0.08. Patients with higher grade of steatosis had higher BMI (32.83+/-6.26 vs. 28.49+/-4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64+/-5.23 vs. 29.90+/-5.35 vs. 27.33+/-4.07, P = 0.008; W/H: 0.97+/-0.06 vs. 0.91+/-0.08 vs. 0.87+/-0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. CONCLUSION: In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.

Falck-Ytter Y, Kale H, Mullen KD, Sarbah SA, Sorescu L, McCullough AJ. · German Cochrane Institute, Stefan-Meier-Strasse 26, 79104 Freiburg, Germany. · Ann Intern Med. · Pubmed #11848726 links to  free full text

Abstract: BACKGROUND: The effect and applicability of interferon-based antiviral therapies in the general population of persons with hepatitis C virus (HCV) infection are unknown. OBJECTIVE: To determine the applicability and usefulness of anti-viral therapy in a metropolitan clinic population. DESIGN: Retrospective case series of consecutively referred patients. SETTING: A teaching county hospital in Cleveland, Ohio. PATIENTS: 327 patients referred to a liver clinic after a positive result for antibody against HCV on enzyme-linked immunosorbent assay (ELISA). MEASUREMENTS: Treatment rates; reasons for nontreatment. RESULTS: 34 patients had no detectable HCV RNA. Of the remaining 293 patients, 72% were not treated for the following reasons: 37% did not adhere to evaluation procedures, 34% had medical or psychiatric contraindications, 13% had ongoing substance or alcohol abuse, 11% preferred no treatment, and 5% had normal liver enzyme levels. Only 83 patients (28%) were treated; 13% had a sustained viral response. CONCLUSION: Most patients with HCV infection are not candidates for interferon-based therapies; alternative interventions should be sought for these patients.

Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. · Department of Gastroenterology, Cleveland, Ohio, USA. · Gastroenterology. · Pubmed #10348825 No free full text.

Abstract: BACKGROUND & AIMS: The spectrum of nonalcoholic fatty liver disease ranges from fatty liver alone to nonalcoholic steatohepatitis. Most previous studies have short follow-up and have not carefully delineated different histological types when determining clinical outcomes. The aim of this study was to compare clinical characteristics and outcomes of patients with different types of nonalcoholic fatty liver. METHODS: All liver biopsy specimens from 1979 to 1987 with fat accumulation were assessed for inflammation, ballooning degeneration, Mallory hyaline, and fibrosis. Biopsy specimens were also assessed for histological iron and hepatitis C RNA. Outcomes were cirrhosis, mortality, and liver-related mortality. RESULTS: Of 772 liver biopsy specimens, complete data were available in 132 patients. Fatty liver (type 1) did not differ from the other three types combined with respect to gender, race, age, or obesity. Cirrhosis was more common in the other types combined (22%) than fatty liver alone (4%; P </= 0.001). Overall mortality, histological iron, and hepatitis C did not differ between groups. Most of the liver-related deaths were in type 4. CONCLUSIONS: The outcome of cirrhosis and liver-related death is not uniform across the spectrum of nonalcoholic fatty liver. These poor outcomes are more frequent in patients in whom biopsies show ballooning degeneration and Mallory hyaline or fibrosis.

Imperiale TF, O'Connor JB, McCullough AJ. · No affiliation provided · Am J Gastroenterol. · Pubmed #10520875 No free full text.

This publication has no abstract.