Progression Of Hepatic Fibrosis In Patients Research Articles

The Rate of Hepatic Fibrosis Progression in Patients Post-Fontan.

This investigation analyzed the rate of hepatic fibrosis progression in post-Fontan patients that underwent hepatic biopsy. The study cohort comprised post-Fontan patients that underwent cardiac catheterization and transvenous liver biopsy between March 2012 and September 2019. We identified 126 patients that met inclusion criteria. Of the 126, 27 (21%) had a lateral tunnel Fontan, and 99 (79%) had an extracardiac Fontan. For the 27 lateral tunnel Fontan patients, age at Fontan was 4 ± 2years, and for the 99 extracardiac Fontan patients age at Fontan was 4 ± 2years (p = 0.98). For the 27 lateral tunnel Fontan patients, the average total fibrosis score was 3.0 ± 1.5; and for the 99 extracardiac Fontan patients, the average total fibrosis was 2.7 ± 1.7 (p = 0.48). For the lateral tunnel Fontan patients, the average Fontan duration was 20 ± 6years; and for the 99 extracardiac Fontan patients, the average Fontan duration was 11 ± 5years (p < 0.001). For the 27 lateral tunnel Fontan patients, the average rate of fibrosis progression was 0.16 ± 0.10 total fibrosis score/year; and for the 99 extracardiac Fontan patients, the average rate of fibrosis progression was 0.30 ± 0.23 total fibrosis score/year (p < 0.001). In conclusion, our findings suggest that those with extracardiac Fontans have a faster rate of hepatic fibrosis progression than those with lateral tunnel Fontans. More extensive or multi-institutional studies will be needed to confirm these findings and define the clinical significance of discrepant rates of hepatic fibrosis in post-Fontan patients.

Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Could Not Always Predict Early Cirrhosis in Non-Viral Liver Diseases.

Background: Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) is a novel non-invasive marker of liver fibrosis. The goal of the study was to investigate whether the novel serum biomarker WFA(+)-M2BP or other non-invasive markers are useful for the prediction of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC). Methods: We examined a significant correlation between serum WFA(+)-M2BP levels and histological staging of fibrosis in several chronic liver diseases, such as NASH, AIH, and PBC. Results: WFA(+)-M2BP could not predict hepatic fibrosis in these patients. We also showed that the level of platelet counts is a useful predictor of hepatic fibrosis progression in patients with NASH, AIH, and PBC. There was a significant correlation between staging of fibrosis and grading of activity in the liver in all groups except for AIH patients. Conclusion: Platelet counts can predict hepatic fibrosis in patients with NASH, AIH, or PBC. Clinicians should pay attention to the grading of liver activity in the use of WFA(+)-M2BP.

The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients.

Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients. Genomic deoxyribonucleic acid from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was genotyped to determine the presence of human platelet antigens-1, -3, or -5 polymorphisms. Fibrosis progression was evaluated using the Metavir scoring system, and the patients were assigned to two groups, namely, G1 that comprised patients with F1, portal fibrosis without septa, or F2, few septa (n = 23) and G2 that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13). Fisher's exact test was utilized to determine possible associations between the human platelet antigen polymorphisms and fibrosis progression. There were no deviations from the Hardy-Weinberg equilibrium in the human platelet antigen systems evaluated. Statistically significant differences were not observed between G1 and G2 with respect to the distributions of the allelic and genotypic frequencies of the human platelet antigen systems. The greater stimulation of hepatic stellate cells by the human immunodeficiency virus and, consequently, the increased expression of transforming growth factor beta can offset the effect of human platelet antigen polymorphism on the progression of fibrosis in patients coinfected with the human immunodeficiency virus-1 and the hepatitis C virus.

TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD.

Insulin resistance and liver fibrosis progression in patients with chronic hepatitis C virus infection

Background and study aims Hepatitis C virus (HCV) infection can predispose to development of insulin resistance before diabetes occurs. Such a potential link is particularly cogent in light of recent data indicating that diabetes might be associated with increased hepatic fibrosis progression in patients with chronic HCV infection. This study aims to determine the prevalence of insulin resistance in non-diabetic patients with chronic hepatitis C and its relation to liver fibrosis. Patients and methods This study included a cohort of 38 patients with chronic liver diseases. They were subdivided into two groups: chronic hepatitis C (CHC) with elevated liver enzymes and CHC with normal liver enzymes. Twelve age- and sex-matched healthy subjects were considered as the control group. The cohort was subjected to careful history and complete examination stressing upon the signs and symptoms of chronic liver diseases. Investigations include liver function tests, viral markers (anti-HCV antibodies and polymerase chain reaction (PCR) for HCV), serum fasting glucose, serum fasting insulin and homeostasis model assessment (HOMA), liver biopsy and abdominal ultrasound. Results Liver fibrosis was found to be considerably more severe among HCV patients with elevated serum transaminases levels. No correlation between viral load and hepatic fibrosis in HCV-infected patients was found. Insulin resistance was present in HCV-infected cases compared with the control group and it correlated with liver fibrosis positively. Conclusion The present data support the hypothesis that insulin resistance may increase the rate of fibrosis progression in non-diabetic patients with chronic HCV. Follow-up of hyperinsulinaemia by serial measurement of HOMA test in non-diabetic HCV-infected patients may be a biochemical indicator for progression of liver fibrosis.

Reply: Outcome of recurrent hepatitis C virus after liver transplantation in a randomized trial of tacrolimus monotherapy versus triple therapy

We read with interest the article by Manousou and colleagues,1 investigating the impact of tacrolimus monotherapy (MT) versus triple therapy (TT) on recurrent hepatitis C infection after liver transplantation. This study examined hepatic fibrosis progression in patients randomized to tacrolimus MT versus corticosteroid, tacrolimus, and azathioprine TT. Seventeen of 54 patients (31.4%) in the MT group and 10 of 49 patients (20.4%) in the TT group reached Ishak stage 4 (S4) over a median of 26 and 39 months, respectively. In multivariate analysis, randomization to MT (odds ratio = 0.7, 95% confidence interval = 0.066-0.847) and a diagnosis of acute hepatitis (odds ratio = 3.59, 95% confidence interval = 1.108-9.823) were associated with S4. Acute hepatitis was more common in the MT group (17/54) than in the TT group (8/49) over a median of 4.4 and 4.8 months, respectively. The authors concluded that TT prolongs graft survival. This may be an overinterpretation because the authors failed to demonstrate statistically significant differences in mortality (16.7% MT versus 12.2% TT) or retransplantation rates (9.6% with MT versus 7.8% with TT) between the groups. TT appeared to delay the progression to S4, but this did not translate into improved graft survival. In addition, we are uncertain from the present study whether delayed hepatic fibrosis progression is related to azathioprine or corticosteroid use. Five-year graft survival in hepatitis C virus-positive transplant recipients is poor (56%).2 A study by Berenguer et al.3 showed improved outcomes for hepatitis C virus recurrence after liver transplantation through the use of 2 immunosuppressants (calcineurin inhibitors with corticosteroids) with a slow tapering of corticosteroids over 9 to 12 months. The present findings of Manousou et al.1 are intriguing, but a study comparing the outcomes with low-dose prednisolone and tacrolimus versus the outcomes with TT is needed to determine which combination of immunosuppressive agents is best in this challenging group of patients. Dinesh Jothimani*, Timothy J. S. Cross*, * Southwest Liver Unit, Hepatology Department, Derriford Hospital, Plymouth Devon, United Kingdom.