the changes in serum levels of hepatic fibrogenesis markers We serially measured the levels of serum N-terminal caused by interferon therapy for chronic hepatitis. 9,10 peptide of type III procollagen (PIIINP), the 7S domain
In this study, the serum levels of PIIINP, IV-7S, and HA of type IV collagen (IV-7S), and hyaluronate (HA) before were determined before, during, and after interferon therapy (0 month), at the end (6 months), and 24 weeks after the in chronic hepatitis type C, and the relationship between the end of interferon therapy (12 months) in patients with levels of these markers and the effectiveness of interferon chronic hepatitis type C to estimate the effects of intertherapy was investigated. feron alfa (IFN-a) on serum levels of hepatic fibrogenesis markers. One hundred twenty-one patients with chronic PATIENTS AND METHODS hepatitis type C received intramuscular injection of 6 million U of natural IFN-a for 24 weeks. Patients were Patients. The subjects included 121 (89 men and 32 women; age, divided into three groups: sustained complete response 21-67 years) who had persistently elevated ALT levels (more than (CR-S), complete response with rebound (CR-R), and 1.5 times the normal upper limit; the normal levels of ALT range nonresponse (NR). Serum PIIINP, IV-7S, and HA levels between 8 and 35 IU/L) for at least 6 months. The mean ALT level were significantly decreased and reached normal levels at initiation of IFN-a therapy was 115.2 { 77.6 IU/L (mean { SD). at 12 months in CR-S; only IV-7S levels were significantly All patients were positive for HCV RNA (assayed by RT-PCR using primers derived from the 5-untranslated region) and anti-HCV (as-decreased at 12 months in CR-R, whereas these levels sayed by Abbott HCV-EIA second-generation kit, Abbott Laboraremained abnormally high in the NR. These results sugtories, North Chicago, IL) in serum. The route of HCV infection ingest that IFN-a therapy could lower the levels of serum cluded blood transfusion in 36 patients, previous acute hepatitis in hepatic fibrogenesis markers along with improvements 14, tattoo in 3, and needle stick in 1 patient. None of the patients had in hepatic inflammation. (HEPATOLOGY 1996;24:27-31.) community-acquired infection. All were seronegative for hepatitis B virus (negative for hepatitis B surface antigen) and autoimmune markers (antinuclear antibody, antimitochondrial antibody, and Interferon alfa (IFN-a) is effective for decreasing serum anti-smooth muscle antibody). None of the patients had received alanine transaminase (ALT) levels and suppressing hepatitis immunomodulatory or antiviral therapy. Patients with alcoholic and drug-induced liver diseases were excluded. Those with evidence of C virus (HCV)-RNA replication in chronic hepatitis type cirrhosis were also excluded. Informed oral consent was obtained C. 1-3 Histological findings also show IFN-a therapy to be an from each patient.
effective treatment for improving lobular and portal inflam-Liver Histological Assessment. Liver biopsy was performed in all mation but not for reducing hepatic fibrosis. 1,2 Recently, the patients with a Tru-cut needle within 1 month before interferon proteins and metabolites of hepatic connective tissue such as therapy, and in 18 patients before and 24 weeks after cessation of N-terminal propeptide of type III procollagen (PIIINP) and therapy. Histological findings of chronic hepatitis were classified into the 7S domain of type IV collagen (IV-7S) were used for monichronic persistent hepatitis (CPH), chronic active hepatitis 2A toring hepatic fibrosis, and these seemed to reflect acceler-(CAH2A), and chronic active hepatitis 2B (CAH2B) according to the ated synthesis or degradation of collagen in the liver. [4][5][6] The international criteria proposed by Groote et al. 11 CPH is character- ized by chronic inflammatory infiltration, mostly portal, with pre-serum levels of PIIINP appear to be the most acceptable served lobular architecture and little or no fibrosis. Piecemeal necromarker of fibrolysis and fibrogenesis in the liver. 4,5 Type IV sis is absent or slight. CAH shows chronic inflammatory infiltration collagen is a major component of the basement membrane, involving the portal tract and extending into the parenchyma, with and the serum levels of IV-7S are considered to be related to piecemeal necrosis and formation of intralobular septa. Architecture endothelial capillarization. 6 The serum levels of hyaluronate is disturbed but there is no nodular regeneration. Activity, as shown (HA) have also been reported to reflect the degree of sinusoid by piecemeal necrosis and inflammation, varied from moderate (2A) fibrous capillarization. 7,8 Quantification of serum HA may to severe (2B). Histological findings showed the features of CPH in provide useful information about endothelial cell function in 29 patients, CAH2A in 61 patients, and CAH2B in 31 patients. Liver the liver as it partially reflects sinusoid fibrous capillarizabiopsy specimens were evaluated and scored with respect to piece- meal necrosis, intralobular inflammation, portal inflammation, and tion. 7,8 However, there is a paucity of information concerning fibrosis according to the histological activity index of Knodell et al. 12 IFN-a Therapy and Definition of Response. Patients received intramuscular injection of 6 million U of natural IFN-a (Sumiferon; Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan) every day for 2 weeks Abbreviations: IFN-a, interferon alfa; ALT, alanine transaminase; HCV, hepatitis C and then three times a week for 22 weeks. The patients treated with virus; PIIINP, N-terminal peptide of type III procollagen; IV-7S, 7S domain of type IV collagen; HA, hyaluronate; CPH, chronic persistent hepatitis; CAH2A, chronic active hepati-interferon were divided into three groups according to ALT levels tis 2A; CAH2B, chronic active hepatitis 2B; CR, complete response; CR-S, sustained com-and HCV RNA in serum: complete response (CR) was defined as plete response; CR-R, complete response with rebound; NR, nonresponse; mRNA, messenger both normalization of ALT levels and negativity for HCV RNA in RNA.