Fibrosis regression and innovative antifibrotic therapies: from bench to bedside

Background: Hepatitis C virus (HCV) is an important cause of chronic hepatitis with necroinflammation and fibrosis resulting in end stage liver disease and hepatocellular carcinoma. Direct acting antivirals (DAAs) are newer agents that directly interfere with the HCV lifecycle and result in high rates of sustained virologic response (SVR). We evaluated if treatment with DAAs in a real-world setting is as successful in HCV/HIV coinfected patients as it is in HCV monoinfected patients, and if some degree of fibrosis regression can be observed after completion of therapy in both groups. Methods: We retrospectively reviewed data from HCV monoinfected and HCV/HIV coinfected patients who received treatment from 2014-2016 at the East Carolina University Infectious Diseases clinic. The primary outcome was to compare completion and sustained virologic response (SVR) rate at either 12 or 24 weeks between HCV monoinfected patients and HCV/HIV coinfected patients. The secondary outcome was to assess regression of fibrosis at either 12 or 24 weeks after completion of therapy, defined as one METAVIR stage improvement in their FibroSure™, a noninvasive biochemical test to estimate the stage of fibrosis. Results: There were 41 patients in each group. Compared to the coinfected group, patient no show rate was higher in the monoinfected group (p=0.0346). In the HCV monoinfected group, 25 (93%) achieved either SVR 12 or 24. Two patients were non-compliant and had detectable viral load on evaluation at week 12. In the HCV/HIV coinfected group, 37 patients achieved SVR (p=0.0039). One patient in the coinfected group did not complete therapy but achieved SVR. In terms of fibrosis, 12/18 (67%) in the monoinfected group demonstrated improvement in at least 1 Metavir stage and 6/18 (33%) had no change. In the coinfected group, 8/16 (50%) patients demonstrated an improvement in FibroSure™ stage, 5/16 (31%) had no change, and 3/16 (19%) had worsening fibrosis according to FibroSure™ stage, (p=0.4867). Conclusions: In this small, real-world cohort, HCV/HIV coinfected patients treated with DAAs had higher completion and SVR rates than HCV monoinfected patients. Treatment failures in the monoinfected group were all linked to non-adherence, whereas, more coinfected patients achieved SVR, likely related to the fact that they were regularly engaged in routine HIV care. Fibrosis regression based on FibroSure™ was observed more in monoinfected patients than those with coinfection. Although not statistically significant, at least 50% of the patients in each group had regression of fibrosis.

Download Full-text

Association of the polymorphism Exon 1 (A/O) region of the mannose-binding lectin gene and periportal fibrosis regression in schistosomiasis after specific treatment

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/0037-8682-0145-2020 ◽

2021 ◽

Vol 54 ◽

Author(s):

Saulo Gomes de Oliveira ◽

Ilana Brito Ferraz de Souza ◽

Taynan da Silva Constantino ◽

Paula Carolina Valença Silva ◽

Elker Lene Santos de Lima ◽

...

Keyword(s):

Specific Treatment ◽

Mannose Binding Lectin ◽

Lectin Gene ◽

Periportal Fibrosis ◽

Mannose Binding ◽

Exon 1 ◽

Fibrosis Regression ◽

Binding Lectin

Download Full-text

Tu1478 – Rest-B Study: Liver Fibrosis Regression Assessed by Transient Elastography (TE) in Patients with Chronic Hepatitis B (CHB) on Long Term Maintenance Therapy with Tenofovir Disoproxil Fumarate (TDF)

Gastroenterology ◽

10.1016/s0016-5085(19)40358-2 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1336-S-1337

Author(s):

Hariklia Kranidioti ◽

KANELLOS-RAFAIL KOUSTENIS ◽

Adonis A. Protopapas ◽

Theodoros Voulgaris ◽

Chrisostomos Tsolias ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Maintenance Therapy ◽

Chronic Hepatitis B ◽

Tenofovir Disoproxil Fumarate ◽

Transient Elastography ◽

Fibrosis Regression ◽

Term Maintenance

Download Full-text

No evidence of fibrosis regression in HCV/HIV co-infected and HCV monoinfected participants up to 3 years after achieving SVR with DAA treatment: Interim results for the ACTG A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS)

Journal of Hepatology ◽

10.1016/s0168-8278(18)31348-5 ◽

2018 ◽

Vol 68 ◽

pp. S545

Author(s):

M. Peters ◽

M. Kang ◽

R. Murphy ◽

R. Matining ◽

W. Rosenberg ◽

...

Keyword(s):

Cohort Study ◽

Hepatitis C ◽

Viral Hepatitis ◽

Hepatitis C Infection ◽

Viral Hepatitis C ◽

Fibrosis Regression

Download Full-text

Association of TIMP1 Levels and Liver Disease Progression Among HIV/HCV Co-infected, HIV Mono-, HCV Mono-infected, and Healthy Groups from the MASH Cohort (FS09-07-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.fs09-07-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Hyojung Kim ◽

Tan Li ◽

Jacqueline Hernandez ◽

Colby Teeman ◽

Javier Tamargo ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Disease Progression ◽

Infected Group ◽

Tissue Inhibitor Of Metalloproteinase ◽

Funding Sources ◽

Liver Disease Progression ◽

Liver Fibrogenesis ◽

Fibrosis Regression ◽

Mean Differences

Abstract Objectives Antiretroviral therapy has increased life expectancy for HIV infected patients; however, this population is developing chronic illnesses associated with aging. Liver disease is a major cause of non-AIDS mortality, characterized by progressive fibrosis. Infection with HIV and with Hepatitis C Virus (HCV) promotes liver fibrogenesis. Tissue inhibitor of metalloproteinase-1 (TIMP1), inhibits fibrosis regression and is profibrogenic. Association between TIMP1 and liver disease progression in an aging population of HIV/HCV co-infected, HIV mono-infected, HCV mono-infected, and healthy groups from the Miami Adult Studies on HIV (MASH) cohort in Miami, Florida, was investigated. Methods Serum TIMP1 levels were determined by ELISA. A non-invasive estimate of liver fibrosis, FIB-4 score was calculated. Liver fibrosis was defined as FIB-4: Low <1.45, intermediate 1.45 < = FIB-4 < = 3.25, High >3.25. ANOVA with Tukey's test assessed the mean differences of FIB-4 score and TIMP1 level between groups, TIMP1 levels between 3 FIB-4 categories, and the effect of age on FIB-4 and TIMP1. Linear regression predicted the association of FIB-4 score and TIMP-1 level. Results Mean age of the cohort was 54.3 ± 8.1 years with no difference between groups. Mean FIB-4 for HIV/HCV co-infected group was the highest among the 4 groups (P < 0.05). Mean TIMP1 for HIV/HCV co-infected group was also the highest among the 4 groups (P < 0.05). FIB-4 and TIMP1 were associated and remained so (β = 0.01, SE = 0.002, P < 0.001) after adjusting for age. Mean TIMP1 for the high FIB-4 category was the highest among the 3 FIB-4 categories (P < 0.05). There was a direct effect of TIMP1 levels on FIB-4 category (P < 0.001). After adjusting for HIV/HCV co-infection (P < 0.001), HIV infection (P < 0.0001), HCV infection (P < 0.002), non-infection (P < 0.001) and age, the relationship between TIMP1 and FIB-4 remained significant. The adjusted TIMP1 mean for HIV/HCV co-infected group was significantly higher compared to HIV infected (P < 0.0001), HCV infected (P < 0.002), and healthy groups (P < 0.0001), regardless of age. Conclusions Age is a significant factor of liver diseases progression. Our findings of the highest levels of TIMP1 in HIV/HCV co-infected group, which had the highest liver fibrosis regardless of age, supports the role of TIMP1 as a regulator in the progression of hepatic fibrosis. Funding Sources National Institutes on Drug Abuse #5UO1DA040381.

Download Full-text

Association of Hepatitis B Core-Related Antigen and Antihepatitis B Core Antibody With Liver Fibrosis Evolution in Human Immunodeficiency Virus-Hepatitis B Virus Coinfected Patients During Treatment With Tenofovir

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa215 ◽

2020 ◽

Vol 7 (7) ◽

Author(s):

Romuald Cruchet ◽

Lorenza N C Dezanet ◽

Sarah Maylin ◽

Audrey Gabassi ◽

Hayette Rougier ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis B Virus ◽

Antiretroviral Therapy ◽

Liver Fibrosis ◽

Hepatitis B ◽

Advanced Fibrosis ◽

B Virus ◽

Immunodeficiency Virus ◽

Fibrosis Regression

Abstract Background Quantitative hepatitis B core-related antigen (qHBcrAg) or antihepatitis B core antibody (qAnti-HBc) could be useful in monitoring liver fibrosis evolution during chronic hepatitis B virus (HBV) infection, yet it has not been assessed in human immunodeficiency virus (HIV)-HBV-coinfected patients undergoing treatment with tenofovir (TDF). Methods One hundred fifty-four HIV-HBV-infected patients initiating a TDF-containing antiretroviral regimen were prospectively followed. The qHBcrAg and qAnti-HBc and liver fibrosis assessment were collected every 6–12 months during TDF. Hazard ratios (HRs) assessing the association between qHBcrAg/qAnti-HBc and transitions from none/mild/significant fibrosis to advanced fibrosis/cirrhosis (progression) and from advanced fibrosis/cirrhosis to none/mild/significant fibrosis (regression) were estimated using a time-homogeneous Markov model. Results At baseline, advanced liver fibrosis/cirrhosis was observed in 40 (26%) patients. During a median follow-up of 48 months (interquartile range, 31–90), 38 transitions of progression (IR = 7/100 person-years) and 34 transitions of regression (IR = 6/100 person-years) were observed. Baseline levels of qHBcrAg and qAnti-HBc were not associated with liver fibrosis progression (adjusted-HR per log10 U/mL = 1.07, 95% confidence interval [CI] = 0.93–1.24; adjusted-HR per log10 Paul-Ehrlich-Institute [PEI] U/mL = 0.85, 95% CI = 0.70–1.04, respectively) or regression (adjusted-HR per log10 U/mL = 1.17, 95% CI = 0.95–1.46; adjusted-HR per log10 PEI U/mL = 0.97, 95% CI = 0.78–1.22, respectively) after adjusting for age, gender, duration of antiretroviral therapy, protease inhibitor-containing antiretroviral therapy, and CD4+/CD8+ ratio. Nevertheless, changes from the previous visit of qAnti-HBc levels were associated with liver fibrosis regression (adjusted-HR per log10 PEIU/mL change = 5.46, 95% CI = 1.56–19.16). Conclusions Baseline qHBcrAg and qAnti-HBc levels are not associated with liver fibrosis evolution in TDF-treated HIV-HBV coinfected patients. The link between changes in qAnti-HBc levels during follow-up and liver fibrosis regression merits further study.

Download Full-text