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  Predictive value of alanine aminotransferase (ALT) levels for histological findings.
Approximately one third of patients with chronic HCV infection have persistently normal ALT levels; thus, the association between ALT levels and histological hepatic findings is an important issue. Pierre Pradat and colleagues retrospectively reviewed data from 864 HCV RNA-positive patients in a collaborative European study. They observed that virtually all HCV RNA-positive patients with elevated ALT levels had hepatic fibrosis (99% with a METAVIR score of F1, and 76% with a score of F2). In patients with persistently normal ALT levels, 65% had a METAVIR score of at least F1, 26% a score of > A1F1 and 14% a score of F2. These data show that although the degree of hepatic fibrosis is usually mild in patients with persistently normal ALT levels, some show more marked histological disease and thus current indications for liver biopsy should be revisited. (Pradat P, et al. Hepatology 2002;36:973-977)
Cryoglobulinemia and cirrhosis.
Zeid Kayali and coworkers conducted a meta-analysis of 19 studies of patients with chronic HCV (n=2,323) published between 1994 and 2001 to investigate if the development of detectable serum cryoglobulins is predictive of progressive liver disease. Cryoglobulinemia was identified in 1,022 (44%) patients. Cirrhosis was present in 40% of patients with cryoglobulinemia compared to only 17% of patients without cryoglobulinemia (p<0.001). The odds ratio for the incidence of cirrhosis in cryoglobulinemia-positive vs. cryoglobulinemia-negative patients, after adjusting for age, gender, and estimated duration of disease by logistic regression, was 4.87 (95% CI: 3.32 - 7.15). These analyses indicate that the presence of cryoglobulinemia may be a useful indicator for progressive liver disease in chronic HCV infection. (Kayali Z, et al. Hepatology 2002;36:978-985)
Shortly after hepatitis C was identified, a relationship was established between the virus and mixed cryoglobulinemia (MC). MC is a lymphoproliferative disease of B lymphocytes that is associated with the appearance of a monoclonal gammopathy producing serum rheumatoid factor (RF) and cryoglobulins that form cryoprecipitate (CP) in chilled serum. Although clinical symptoms of MC such as purpura, arthritis, and glomerulonephritis occur infrequently in patients with chronic HCV, over 40% of patients develop CP and nearly 80% develop RF "asymptomatically" during the chronic infection. Although it is accepted that MC is associated with many of the extrahepatic complications of HCV, the relationship between asymptomatic CP and progressive liver disease has been debated. Although the molecular arrangement of CP is poorly understood, it reportedly binds significant quantities of HCV RNA.7,8,12,13 Association of the virus with the CP appears to require specific antibody binding in complex with RF because nonspecific trapping of virus does not appear to occur.7 Viral RNA is enriched in the CP greater than the respective levels in serum,12,13 and whether this viral RNA participates in target cell infection, inflammation, fibrosis, or peripheral blood viral turnover is unknown.
MC is also associated with a wide variety of other chronic disorders, including malignancy and autoimmune and infectious diseases.9,14 Prior to the discovery of HCV, MC that appeared without an apparent underlying disease was considered "essential MC"; however, most of these patients have since been shown to be infected with chronic HCV. Traditionally, cryoglobulins are classified into 3 types.14 Type I cryoglobulins are single, monoclonal immunoglobulins such as those typically seen in Waldenstom's macroglobulinemia. Types II and III contain either a monoclonal (type II) or polyclonal (type III) IgM with RF activity plus polyclonal IgG and are commonly referred to as "mixed MC." Although chronic HCV infection can elicit either a type II or III CP, it is unclear whether either CP subtype is associated with more aggressive liver disease.
Kidney transplantation and liver fibrosis.
The natural history of hepatic fibrosis progression in HCV patients following kidney transplantation remains controversial. Laurent Alric et al. performed a cohort study in which patients who had received kidney transplantation during HCV infection (group 1; n = 30) were matched by factors prognostic for hepatic fibrosis at first liver biopsy with HCV patients undergoing hemodialysis (group 2; n = 30), and nontransplanted, nonhemodialyzed HCV patients (group 3; n = 30). Results from a second liver biopsy revealed that the METAVIR and Knodell scores and the annual rate of fibrosis progression were lower in the kidney transplant group than in group 3 (p <0.01 and p = 0.03, respectively). These findings indicate a low rate of hepatic fibrosis progression in HCV-infected kidney transplant recipients. (Alric L, et al. Gastroenterology 2002;123:1494-1499)
Treatment of recurrent hepatitis C in liver transplant recipients.
Roberto Firpi and associates at the University of Florida report results of treatment of 54 patients with histological recurrence of HCV infection ( F3 and/or Knodell 5) after liver transplantation with combination interferon alfa-2b (3 MU 3 times weekly) and ribavirin (800 to 1,000 mg daily) for 12 months. The mean serum level of HCV RNA detected at baseline was 38 9 mEq/mL, and 88% of patients had genotype 1 infection. Serum HCV RNA became undetectable in 21 patients (38%) at the end of treatment and remained undetectable in 16 patients (30%) 6 months post-treatment. Patients who achieved viral eradication had no significant progression of fibrosis during therapy. Dose modifications due to cytopenia were required in 72% of patients. These results show that combination interferon alfa-2b plus ribavirin therapy can be effective treatment for liver transplant recipients with recurrent HCV. (Firpi R, et al. Liver Transpl 2002;8:1000-1006)
Radiologic imaging in nonalcoholic fatty liver disease (NAFLD).
S. Saadeh and colleagues at the Cleveland Clinic Foundation conducted a study in which consecutive patients with biopsy-proven NAFLD underwent abdominal ultrasonography, computerized topography, and magnetic resonance imaging. The presence of >33% fat on liver biopsy was found to be optimal for detecting steatosis by radiological imaging. However, none of the radiological modalities were able to detect features of nonalcoholic steatohepatitis (NASH) (e.g., hepatocyte ballooning, fibrosis) or distinguish NASH from simple steatosis. These findings demonstrate that although radiologic imaging was able to determine a level of severity of steatosis in the livers of patients with NAFLD, it was not able to detect any distinguishing features of NASH. (Saadeh S, et al. Gastroenterology 2002; 123:745-750)
Coffee intake and risk of gallstone disease.
Coffee affects several metabolic processes involved in cholesterol lithogenesis, and coffee drinking has previously been associated with a lower risk of symptomatic gallstone disease in men. M. Leitzmann et al. prospectively examined the association of coffee drinking and cholecystectomy in a cohort of 80,898 women aged 34 to 59 years. During 20 years of follow-up (from 1980 to 2000) 7,811 women had a cholecystectomy. The multivariate relative risks (adjusted for risk factors) of cholecystectomy for those who consistently drank 0, 1, 2-3, and 4 cups of caffeinated coffee daily were 1.0, 0.91, 0.78, and 0.72, respectively (p<0.0001 for the decreasing trend). The intake of decaffeinated coffee was not associated with a decreased risk of cholecystectomy. These data suggest that the consumption of caffeinated coffee may decrease the risk for symptomatic gallstone disease in women. (Leitzmann MF, et al. Gastroenterology 2002;123:1823-1830)
Thanks to Hepatitis Watch- (http://www.hepwatch.com/January2003.htm)- JANUARY 2003
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