A total of 203 patients with chronic liver diseases who had a checkup in Kurume University Hospital from March 1, 2007 to July 31, 2008 received advice about the therapeutic effects of, and methods of purchasing, Aminofeel®. Each patient was free to decide whether to purchase and take Aminofeel®. We excluded 15 patients whose uptake rates were below 70%.
Among the remaining 188 patients, there were 51 who received IFN therapy. Thirty five patients took Aminofeel® and 16 did not. Thirty seven patients received IFN treatment with the aim of eradicating HCV and 14 received low-dose, long-term (maintenance) IFN treatment aimed at suppression of hepatocarcinogenesis. Natural IFN alpha, IFN beta or Peg-IFN alpha 2a was selected for IFN monotherapy. Combined standard therapy of Peg-IFN alpha 2b or 2a and RBV was given for 24 to 72 weeks.
Group 1 (standard IFN therapy)
Among the 37 patients who received IFN therapy to eradicate HCV, 24 (group 1-A) took Aminofeel® during therapy and 13 (group 1-B) did not (Table 1). Group 1-A ranged in age from 50 to 74 years, with an average of 62.3 ± 5.5 years. Group 1-B ranged in age from 26 to 75 years, with an average of 57.5 ± 12.6 years.
The diagnosis of liver disease in group 1-A included: chronic hepatitis C (n=16), chronic hepatitis C and hepatitis B (n=1), chronic hepatitis C with post-treatment of HCC (n=2), HCV-related liver cirrhosis (n=1), and HCV-related liver cirrhosis with post-treatment of HCC (n=4). Those of group 1-B included: chronic hepatitis C (n=11), chronic hepatitis C and hepatitis B (n=1), and HCV-related liver cirrhosis with post-treatment of HCC (n = 1).
The end-point was the achievement of the adherence to IFN and/or RBV therapy, defined as the receipt of ≥ 80% of scheduled IFN and/or RBV doses for ≥ 80% of the scheduled treatment period.
Group 2 (low-dose, long-term IFN therapy)
Low-dose long-term (maintenance) IFN, usually Peg-IFN alpha 2a, was administered to 14 patients who were difficult to treat, because of no effect or harmful side effects with standard IFN therapy, and who had advanced liver fibrosis (Table 3). Among the 14, 11 patients (group 2-A) took Aminofeel® during therapy and 3 (group 2-B) did not. Group 2-A ranged in age from 56 to 73 years, with an average of 65.2 ± 5.9 years. Group 2-B ranged in age from 58 to 70 years, with an average of 64.3 ± 6.0 years.
The diagnosis of liver disease in group 2-A included: chronic hepatitis C (n=1), chronic hepatitis C and autoimmune hepatitis (n=1), chronic hepatitis C with post-treatment of HCC (n=1), HCV-related liver cirrhosis (n=5), HCV and HBV-related liver cirrhosis (n=1), and HCV-related liver cirrhosis with post-treatment of HCC (n=2). Those of group 2-B included: chronic hepatitis C with post-treatment of HCC (n=1), and HCV-related liver cirrhosis with post-treatment of HCC (n=2).
All patients were tested for red blood cell (RBC), white blood cell (WBC), platelets (PLT), hemoglobin (Hb), and insulin resistance index (IRI), zinc (Zn), fasting blood glucose (FBS) and HbA1c, and for the following liver function tests: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (gamma GTP), cholinesterase (ChE), prothrombin time (PT), total bilirubin (T. Bil), total cholesterol (TC), total protein (TP), and albumin (Alb). The formula for the HOMA-IR is: HOMA-IR = FBS × fasting insulin/405. The formula for the HOMA-beta is: HOMA-beta = 360 × fasting insulin/FBS-63.
Evaluation of liver diseases
Anti-HCV was measured using a chemiluminescent enzyme immunoassay kit (Lumipulse II HCV, Fujirebio, Tokyo, Japan). HCV RNA in serum was analyzed by the Amplicor HCV test (Roche, Tokyo, Japan) up to December 6, 2007 and by quantitative PCR assay (COBAS AMPLICOR HCV MONITOR v 2.0 Test, COBAS AmpliPrep/COBAS Taq-Man HCV Test, Roche Molecular Systems, New Jersey, US) from December 7, 2007 [32, 33]. HCV genotype was determined by polymerase chain reaction assay, using a mixture of primers for the subtype, as reported previously . HBsAg was assayed using a chemiluminescent immunoassay kit (Architect, HBsAg QT, Dainabot, Tokyo, Japan). All patients were examined using hepatic ultrasonography, computed tomography, or magnetic resonance imaging in order to investigate the shape of the liver and lesions occupying the liver. Liver biopsy was performed on some patients.
Evaluation of extrahepatic diseases
IFN therapy may cause or worsen such immunological diseases or extrahepatic diseases. We examined theses diseases before IFN therapy. A diagnosis of oral lichen planus was made on the basis of clinical and/or histopathological features. Obesity was defined as a body mass index (BMI) ≥ 25 kg/m2. Diagnosis of type 2 DM was based on the American Diabetic Association (ADA) criteria of 1997 . Hypertension was defined as a systolic blood pressure (SBP) of 140 mmHg or higher or a diastolic blood pressure (DBP) of 90 mmHg or higher, according to the criteria of JNC-VI of the International Hypertension Society . Thyroid hormones such as FT3, FT4 and thyroid stimulating hormone were measured for all patients and thyroid echography examination was performed for some patients. Examination of the upper or lower gastrointestinal tract was performed on patients for whom it was deemed clinically necessary.
The retrospective study was approved by the Ethics Committee of Kurume University on August 4, 2008 (reference number: 06046) in accordance with the Declaration of Helsinki.
All data are expressed as mean ± standard error. Differences between the two groups were analyzed using the Mann–Whitney U test, Wilcoxon’s test, and Fisher’s exact test. Differences were judged significant for p ≤ 0.05 (two-tailed). P value was rounded off to two decimal places. Adjusted odds ratios were calculated using logistic regression analysis. All statistical analyses were conducted using JMP Version 6 (SAS Institute, Cary, NC, USA). The level of statistical significance was defined as 0.05.