The prediction of liver disease status using Doppler observations of the hepatic and portal venous system compared with liver biopsy in patients with chronic hepatitis C

This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1β, IL-15, IFN-γ, IL-4, IL-10, TGF-β, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-βand suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.

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A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs

Blood ◽

10.1182/blood.v78.7.1672.bloodjournal7871672 ◽

1991 ◽

Vol 78 (7) ◽

pp. 1672-1677 ◽

Cited By ~ 1

Author(s):

M Makris ◽

FE Preston ◽

DR Triger ◽

JC Underwood ◽

L Westlake ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Hepatitis C ◽

Liver Biopsy ◽

Chronic Hepatitis C ◽

Interferon Alpha ◽

Recombinant Interferon ◽

Randomized Controlled ◽

Ifn Alpha ◽

Recombinant Interferon Alpha

Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self- administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon- treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C.

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A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs

Blood ◽

10.1182/blood.v78.7.1672.1672 ◽

1991 ◽

Vol 78 (7) ◽

pp. 1672-1677 ◽

Cited By ~ 69

Author(s):

M Makris ◽

FE Preston ◽

DR Triger ◽

JC Underwood ◽

L Westlake ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Hepatitis C ◽

Liver Biopsy ◽

Chronic Hepatitis C ◽

Interferon Alpha ◽

Recombinant Interferon ◽

Randomized Controlled ◽

Ifn Alpha ◽

Recombinant Interferon Alpha

Abstract Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self- administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon- treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C.

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Histological and Clinical Characteristics of Patients with Chronic Hepatitis C and Persistently Normal Alanine Aminotransferase Levels

Hepatitis Research and Treatment ◽

10.1155/2014/760943 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Bakht Roshan ◽

Grace Guzman

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Hepatitis C ◽

Liver Biopsy ◽

Chronic Hepatitis C ◽

Alanine Aminotransferase ◽

Activity Index ◽

Medical Center ◽

Significant Difference ◽

Normal Alanine Aminotransferase

Patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase (PNALT) are generally described to have mild liver disease. The aim of this study was to compare clinical and histological features in HCV-infected patients with PNALT and elevated ALT. Patients presenting to the University of Illinois Medical Center, Chicago, who had biopsy proven HCV, an ALT measurement at the time of liver biopsy, at least one additional ALT measurement over the next 12 months, and liver biopsy slides available for review were identified. PNALT was defined as ALT ≤ 30 on at least 2 different occasions over 12 months. Of 1200 patients with HCV, 243 met the study criteria. 13% (32/243) of patients had PNALT while 87% (211/243) had elevated ALT. Significantly more patients with PNALT had advanced fibrosis (F3 and F4) compared to those with elevated ALT (P=0.007). There was no significant difference in the histology activity index score as well as mean inflammatory score between the two groups. In conclusion, in a well-characterized cohort of patients at a tertiary medical center, PNALT did not distinguish patients with mild liver disease.

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Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C

Blood ◽

10.1182/blood-2001-12-0192 ◽

2002 ◽

Vol 99 (12) ◽

pp. 4588-4591 ◽

Cited By ~ 101

Author(s):

Eliseo Minola ◽

Daniele Prati ◽

Fredy Suter ◽

Franco Maggiolo ◽

Flavio Caprioli ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Hepatitis C ◽

Liver Biopsy ◽

Confidence Interval ◽

Chronic Hepatitis C ◽

Hcv Infection ◽

Hcv Rna ◽

Term Outcome ◽

Long Term Outcome

Before the introduction of hepatitis C virus (HCV) screening for blood donors, the risk of acquiring HCV infection as a result of a transfusion was about 10%. The aim of this study was to assess the frequency and rate of progression to cirrhosis in patients with transfusion-associated chronic HCV infection and identify possibly negative prognostic factors. Of 2477 consecutive patients with clinical or laboratory evidence of liver disease, 392 (16%) were anti-HCV– and HCV-RNA–positive, had anamnestic evidence of a single and precisely dated transfusion event, and showed no other causes of chronic liver disease; 268 (68%) underwent ultrasound-guided liver biopsy and were enrolled in the study. After a mean interval of 18.4 years, 54 patients (20.1%) had cirrhosis, which multivariate analysis showed to be independently associated with the duration of follow-up, age at infection and at the time of liver biopsy, and serum alanine aminotransferase levels at biopsy. The time necessary to have a 50% probability of developing cirrhosis in patients aged 21-30, 31-40, and more than 40 years was 33, 23, and 16 years, respectively. In comparison with those aged 20 years or less at infection, the risk ratio of developing cirrhosis over a period of 30 years for patients aged 21-30 and at least 31 years at infection was, respectively, 4.51 (95% confidence interval, 1.03-19.76) and 12.29 (95% confidence interval, 3.06-49.40). In patients with transfusion-associated chronic hepatitis C, the risk of cirrhosis is related to age at infection and disease activity. Our findings suggest that an aggressive therapeutic approach should be adopted in patients infected by HCV at an older age to prevent the progression to end-stage liver disease.

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