Rapid Progression Of Liver Fibrosis Research Articles

Contagious order as a risk factor for liver fibrosis progression in co-infection with human immunodeficiency virus, hepatitis B and C viruses

In triple co-infection with HIV/HCV/HBV, the prognosis is significantly poorer and life expectancy is lower because of the rapid progression of liver fibrosis or development of hepatocellular carcinoma. The aim of this study was to test the hypothesis that one of the risk factors for the unfavorable course of HIV/HCV/HBV co-infection is contagious order and the interval between coinfections. The study analyzed anamnestic data and the results of direct follow-up of 97 patients co-infected with HIV/HCV/HBV for 1-2 years. Patients were divided into three study groups: (1) HIV as the first pathogen, (2) HCV as the first pathogen, and (3) HBV as the first pathogen. For each patient, the period (in years) between the acquisition of the first and subsequent pathogens was considered. During the fol-low-up period, viral HIV, HCV, and HBV load was assessed by PCR, and annual transient liver fibro-elastometry was performed to determine the fibrosis stage using the METAVIR scoring system. The risk of progressive liver fibrosis in HIV/HCV/HBV co-infection is higher when HIV or HBV is the first pathogen, but the interval between the acquisition of HBV and other viruses is 10 years. Meanwhile, a stable course of liver fibrosis is associated with an HBV viral load of >7,200 copies/ml. In the risk group, the most effective antiretroviral therapy was a combination of reverse transcriptase inhibitors, HIV protease inhibitors, and direct antiviral (anti-HCV) drugs. Therefore, the order of infection and intervals between pathogen acquisition in triple co-infection with HIV/HCV/HBV have a significant effect on liver fibrosis progression, which requires specific approaches to the organization of diagnostic tests and the control of antiretroviral therapy.

Galectin-3 in biliary atresia and other pediatric cholestatic liver diseases.

Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin-3, a beta-galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin-3 levels in children with BA. Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin-3 was measured using standard enzyme-linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing. Plasma Galectin-3 in late BA was significantly higher than in early BA (20.82 [12.45-30.46] vs. 11.30 [8.74-16.83] ng/mL, p=0.0096). Galectin-3 levels correlated with markers of disease severity and interleukin-6. There were significantly more Galectin-3+ M2 macrophages in late BA in comparison to late other CLD (162 [157-233] vs. 49 [33-59] cells/mm2, p=0.03). The number of Galectin-3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation. Plasma Galectin-3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin-3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin-3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA.

The using of genetic markers as a possibility of predicting the rate of progress of liver fibrosis in patients with chronic hepatitis B

According to recent WHO estimates, chronic HBV infection is one of the leading causes of death and disability in patients with infectious diseases. From 780 thousand to 1 million deaths are annually recorded in the world as a result of cirrhosis of the liver and hepatocellular carcinoma. Pathogenetic features of the course and outcomes of chronic hepatitis B are determined by the immunological, genetic factors of the host, as well as the molecular biological structure of the virus. The aim of the work was to study the interaction of polymorphic loci of the cytokine genes SMAD 7 (rs4939827), TNFα (rs1800620), IL-10 (rs1800896), IL-4 (rs2243250) and the degree of structural changes in the liver based on the non-invasive Fibrotest technique in patients with chronic hepatitis B as part of a search for possible predictors of predisposition to the rapid progression of liver fibrosis. The study included 82 patients with chronic hepatitis B. Assessment of morphological changes (stage of fibrosis) was carried out by the method of non-invasive diagnosis of FibroScan, which is an alternative to puncture biopsy of the liver. It has been suggested that homozygous alleles СС IL-4 (rs2243250), GG TNFα (rs1800620), СС SMAD family member 7 (rs4939827) have a protective effect on the course of chronic hepatitis B, as these variants of allelic polymorphism of cytokine genes were found mainly in patients with CHB with a degree of fibrosis F0-F1. The heterozygous genotypes СТ IL-4 (rs2243250) and GA TNFα (rs1800620), the mutant homozygous ТТ SMAD family member 7 (rs4939827) have a profibrotic effect on the course of chronic hepatitis B, as they are found mainly in patients with chronic hepatitis B with degree of fibrosis F3. The established relationship between the liver fibrosis stage according to the METAVIR scale and the polymorphism of the cytokine genes SMAD 7 (rs4939827), TNFα (rs1800620) and IL-4 (rs2243250) made it possible to create a prognostic scale for assessing the individual risk of rapid progression of liver fibrosis. The proposed scale, due to a comprehensive assessment of the polymorphism of cytokine gene alleles and the stage of liver fibrosis using the METAVIR scale, makes it possible to carry out an individual assessment of the risk of progression of chronic hepatitis and, possibly, draw up a personalized treatment plan for the patient. Coding of the studied polymorphisms and subsequent counting can be automated, which does not require significant financial investments. The possibilities of the prognostic scale are proven on the example of a group of patients who received the antifibrotic agent bicyclol in comparison with the control group.

Level of IL-6 and IL-8 and their associations with non-alcoholic fatty liver disease in patients with type 2 diabetes

non-alcoholic fatty liver disease (NAFLD) is indicated by the accumulation of lipids within the hepatocytes exceeding 5% of liver weight without excessive alcohol intake and secondary liver diseases. The efforts of many scientists worldwide are focused on improving the understanding of pathogenic processes and triggers of NAFLD progression, with an emphasis on the simultaneous study of several pathophysiological pathways to identify disorders throughout the disease spectrum. The aim was to examine the serum levels of IL-6 and IL-8 and its associative relationships with anthropometric parameters and metabolic profiles in patients with T2D, depending on the presence of NAFLD. This cross-sectional study involved 375 patients aged 40–80 with type 2 diabetes. They were divided into 3 groups. The control group included 98 T2D patients without NAFLD. The main group included T2D patients with NAFLD, which was separated into two subgroups depending on the level of transaminases: normal (group 2A, n=150) and increased (group 2B, n=127) transaminases group. In order to identify predictors of rapid progression of liver fibrosis in patients with T2D, a sub-analysis was conducted, which included 82 patients from group 2. We found significant relationships between the level of studied interleukins and the components of the metabolic syndrome. Both IL-6 and Il-8 levels are significantly associated with gender, duration and severity of T2D, BMI, ALT, AST and total bilirubin level in a simple logistic regression analysis. However, step-by-step multiple logistic regression analysis revealed no reliable link between both cytokines and NAFLD development. From the other hand elevated IL-8 and decreased IL-6 had a significant effect on the fibrosis progression in patients with NAFLD associated with T2D. Our study has demonstrated significant links between the level of IL-6 and IL-8 and the components of the metabolic syndrome such as obesity or transaminase activity, but not with NAFLD itself.

Development of liver inflammatory injury in biliary atresia: from basic to clinical research.

Biliary atresia (BA) is a severe cholangiopathy in infants. It is characterized by inflammatory fibro-obliteration of the intra- and extrahepatic bile ducts. Although the restoration of bile flow can be successful after Kasai operation, the rapid progression of liver fibrosis can continue, leading to cirrhosis. It is believed that the progression of liver fibrosis in BA is exacerbated by complicated mechanisms other than the consequence of bile duct obstruction. The fibrogenic cascade in BA liver can be divided into three stages, including liver inflammatory injury, myofibroblast activation, and fibrous scar formation. Recent studies have revealed that the activation of an immune response following bile duct injury plays an important role in promoting the inflammatory process, the releasing of inflammatory cytokines, and the development of fibrogenesis in BA liver. In this article, we summarized the evidence regarding liver inflammatory injury and the possible mechanisms that explain the rapid progression of liver fibrosis in BA.

Impact of HIV-1 Infection on the Natural Progress of an Anti-HCV Positive Population in an Impoverished Village in China from 2009 to 2017.

Our study aimed to determine the impact of HIV coinfection on the natural progression of liver disease in treatment-naive HCV-infected patients. From 2009 to 2017, we tracked non-invasive markers of liver fibrosis and end-stage liver disease (ESLD)-associated mortality among HCV mono-infected and HIV/HCV coinfected patients in an impoverished village in China. The study cohort consisted of 355 HBsAg-negative and anti-HCV (+) or anti-HIV (+) patients recruited in July 2009, 164 of whom were diagnosed with HIV-1 infection. The surviving patients were re-evaluated in August 2017. During the follow-up, the disease status, liver biochemical, and non-invasive indicators of liver fibrosis (APRI and FIB-4) were measured. The transaminases ALT and AST were significantly higher in HIV-positive HCV resolvers (HIV+ HCVr) than in HIV-negative HCV resolvers (HCVr) (p = 0.019 and p < 0.0001, respectively). APRI and FIB-4 scores of HIV-positive chronic HCV carriers (HIV+ HCVc) were significantly higher than in HIV-negative chronic HCV carriers (HCVc) (p < 0.001). Similarly, APRI and FIB-4 scores were higher in the HIV+ HCVr group than in the HCVr group (ps < 0.001). From 2009 to 2017, the levels of ALT (p = 0.006), AST (p = 0.003), APRI (p = 0.015), and FIB-4 (p = 0.025) were significantly elevated in the HIV/HCV coinfected patients with CD4+ T counts below 500 cells/l. ESLD-related mortality was significantly greater in HIV/HCV-infected cases than in HCV mono-infected patients (73.3% vs. 31.3%, p = 0.009) among patients (n = 45) who died between 2009 and 2017 during follow-up. These findings suggest a higher risk of ESLD-related death and rapid progression of liver fibrosis in HIV/HCV coinfected individuals compared with HCV mono-infected patients. During HIV/HCV coinfection, HIV infection may aggravate HCV-associated liver injury.

Current status and perspectives of the clinical and basic research on concomitant chronic hepatitis B virus infection and nonalcoholic fatty liver disease

Chronic hepatitis B virus infection (CBI) and nonalcoholic fatty liver disease (NAFLD) are the two main etiologies of chronic liver diseases worldwide, and therefore, concomitant CBI and NAFLD (Co-CBI&NAFLD) is relatively common. There are still controversies over the influence of the interaction between CBI and NAFLD, especially NAFLD, on the progression, antiviral response, and outcome of chronic hepatitis B (CHB). Current clinical and basic research on Co-CBI&NAFLD have shown that NAFLD could inhibit HBV DNA replication to a certain degree, manifesting as a relatively low HBV DNA load, and it might increase HBsAg clearance rate in patients with CHB. Prospective or retrospective cohort studies have shown that patients with Co-CBI&NAFLD tend to have more rapid progression of liver fibrosis than those with CHB alone, as well as increased incidence rates of liver cirrhosis and hepatocellular carcinoma. Histologically, Co-CBI&NAFLD has the pathological changes of both CHB and NAFLD, and therefore, it is difficult to identify their own characteristic lesions. At present, the natural history and pathogenesis of Co-CBI&NAFLD remain unclear, and its pathological characteristics have not been fully identified. There is still a lack of high-level evidence-based supporting information on the influence of NAFLD on the course of CHB, especially its impact on antiviral response and disease outcome, and there are also no guidelines for the diagnosis/treatment or management of Co-CBI&NAFLD in China and globally. Solutions to the above issues will definitely deepen the understanding of Co-CBI&NAFLD, standardize and improve clinical diagnosis/treatment or management, and thus reduce the incidence and mortality rates of related end-stage liver diseases.

Genotype 3-hepatitis C virus' last line of defense.

Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.

A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women.

HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.

Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems.

Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.

The Role of the Hepatic Tissue Remodeling Regulators MMP-9 and TIMP-1 in the Progression of Liver Cirrhosis

Objective: to study the level of the hepatic tissue remodeling regulators MMP-9 and TIMP-1 in the blood of patients with the progression of chronic diffuse liver diseases.Material and methods. The object of the study was 80 patients with chronic diffuse liver diseases (chronic hepatitis and cirrhosis). The concentration of MMP-9 and TIMP-1 in the blood of the patients was determined by enzymelinked immunosorbent assay (ELISA).Results: As chronic diffuse liver diseases progressed, a statistically significant decrease in the level of MMP-9 in the blood of the patients was revealed, which was reflected in the decreased intensity of the extracellular matrix resorption processes and transformation of chronic hepatitis into liver cirrhosis. The activity of TIMP-1 which suppressed the fibrolytic effects of MMP-9, was statistically significantly higher in the viral etiology of liver cirrhosis, which probably led to more rapid progression of liver fibrosis associated with the presence of hepatitis C and В viruses.

Optimal timing of hepatitis C treatment among HIV/HCV coinfected ESRD patients: Pre- vs posttransplant.

Patients with end-stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV-infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney-only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre- and posttransplant, were compared using Monte Carlo microsimulation of 1000000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait-time over a lifetime time horizon. Treatment posttransplant was consistently cost-saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0-F1), treatment posttransplant also yielded higher life months (LM) and quality-adjusted life months (QALM), except among F1 candidates with wait times ≥ 18months. For candidates with advanced liver disease (F2-F4), treatment pretransplant afforded more LM and QALM unless wait time was <18months. Moreover, treatment pretransplant was cost-effective for F2 candidates with wait times >71months and F3 candidates with wait times >18months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely.

Matrix stiffness regulate apoptotic cell death in HIV-HCV co-infected hepatocytes: Importance for liver fibrosis progression

HIV-HCV co-infection causes rapid progression of liver fibrosis. These outcomes to liver cirrhosis can be improved, but not stopped by specific antiviral therapies. Due to high significance of HIV-HCV interactions for morbidity and mortality in co-infected patients, our attention was attracted to the multi-component pathogenesis of fibrosis progression as the transition to end-stage liver disease development. In this study, we hypothesize that increased matrix stiffness enhances apoptosis in HCV-HIV-co-infected hepatocytes and that capturing of apoptotic bodies (AB) derived from these infected hepatocytes by hepatic stellate cells (HSC) drives the fibrosis progression. As the source of viruses, JFH1 (HCV genotype 2a) and HIV-1ADA (either purified or containing in infected macrophage supernatants) were chosen. Using Huh7.5-CYP (RLW) cells and primary human hepatocytes mono-infected with HCV and HIV or co-infected, we have shown that both HCV and HIV RNA levels were increased in co-infected cells, which was accompanied by hepatocyte apoptosis. This apoptosis was attenuated by azidothymidine treatment. The levels of both infections and apoptosis were more prominent in primary hepatocytes cultured on substrates mimicking fibrotic stiffness (24 kPa-stiff) compared to substrates mimicking healthy liver (2.4 kPa-soft). The engulfment of AB from pathogen-exposed hepatocytes activated pro-fibrotic mRNAs in HSC. Overall, the increased matrix stiffness is not only a consequence of liver inflammation/fibrosis, but the condition that further accelerates liver fibrosis development. This is attributed to the switching of HSC to pro-fibrotic phenotype by capturing of excessive amounts of apoptotic HCV- and HIV-infected hepatocytes.

Liver Fibrosis Progression in Hepatitis C Virus Infection After Seroconversion

Knowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions. To determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection. Secondary data analysis of persons in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610 514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline. Progression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation. The evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P < .001), a higher prevalence of alcohol and drug abuse and dependence diagnoses, and higher serum aminotransferase levels, but had a lower prevalence of diabetes and hypertension. Fibrosis progression started early after infection among HCV+ persons and tapered off after 5 years. A total of 452 cirrhosis and 85 hepatic decompensation events were recorded. After 10 years of follow-up, HCV+ persons were more likely to have a diagnosis of cirrhosis compared with HCV- controls (18.4% vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%). Persons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.

Management of hepatitis C in patients with chronic kidney disease

Hepatitis C virus (HCV) infection is highly prevalent among chronic kidney disease (CKD) subjects under hemodialysis and in kidney transplantation (KT) recipients, being an important cause of morbidity and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on management and treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon (PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes mellitus.

Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression.

To evaluate steatosis, insulin resistance (IR) and patatin-like phospholipase domain-containing 3 (PNPLA3) and their relation to disease progression in hepatitis B and C viruses (HCV-HBV) co-infected patients. Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled: 66 had HBV-HCV, 66 HBV and 198 HCV infection. Prevalence of steatosis, IR and PNPLA3 polymorphisms and their relation to anthropometric, biochemical, virological and histological parameters were evaluated. Prevalence of steatosis in group HBV-HCV was similar to that in HCV (47.0% vs 49.5%, respectively); group HBV showed the lowest steatosis (33.3%). Group HBV-HCV had a lesser degree of steatosis than HCV (P = 0.016), lower HCV RNA levels (P = 0.025) and lower prevalence and degree of IR (P = 0.01). PNPLA3 polymorphisms were associated with steatosis. Group HBV-HCV showed higher levels of liver fibrosis than group HCV (P = 0.001), but similar to that observed in HBV group. In HBV-HCV group, liver fibrosis was not associated with steatosis, IR or PNPLA3. HBV infection was the independent predictor of advanced liver fibrosis. HBV-HCV co-infected patients have lower degree of hepatic steatosis, IR and HCV RNA than HCV mono-infected; co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.

Update of HCV in HIV-Coinfected Patients: Immunobiology and Current Treatment Options

Chronic hepatitis C virus (HCV) coinfects nearly 25% of HIV patients and it has been associated with more rapid progression of liver fibrosis, leading to cirrhosis, end-stage liver disease and hepatocellular carcinoma. Emerging data support multiple derangements attending HIV coinfection, including increases in profibrogenic cytokine expression and secretion, generation of enhanced oxidative stress, and increases in hepatocyte apoptosis. Furthermore, liver-related death is a major cause of morbidity and mortality in HCV/HIV coinfected patients on antiretroviral therapy therefore, anti-HCV treatment is advised to be considered for all HCV/HIV patients. Unfortunately, treatment with pegylated interferon (PegIFN) plus ribavirin (RBV) has shown a low efficacy in these patients, mainly among those coinfected with genotype 1. Triple therapy with PegIFN plus RBV and telaprevir or boceprevir, the first approved direct-acting antiviral agents (DAAs) will improve the likelihood of cure for genotype 1 infected patients. Nevertheless, a significant number of coinfected patients are ineligible for IFN-containing regimens and concerns remain in regard with drug-to-drug interactions and safety of triple therapy in cirrhotic patients. Furthermore, therapeutic decisions today need take into account the promise of new DAAs, some combined in IFN-free regimens, currently being investigated in multiple clinical trials to be in a near future, an easier, shorter and more effective HCV treatment in HIV coinfected patients. Keywords: Direct antiviral-acting agents, HCV/HIV coinfection, immunobiology, liver fibrosis, PegInterferon, treatment.

Chronic Hepatitis E with Neurologic Manifestations and Rapid Progression of Liver Fibrosis in a Liver Transplant Recipient

Chronic Hepatitis E with Neurologic Manifestations and Rapid Progression of Liver Fibrosis in a Liver Transplant Recipient

Treatment Options for Hepatitis Delta Virus Infection

The hepatitis D virus (HDV), the smallest virus known to infect man, causes the most severe form of chronic viral hepatitis, hepatitis delta. It is estimated that about 15 to 20 million people are suffering from chronic HDV infection. HDV is a defective satellite virus depending on the hepatitis B surface antigen (HBsAg) for transmission. Chronic hepatitis delta is associated with a rapid progression of liver fibrosis and a high prevalence of liver cirrhosis, even in younger patients. Immunization against hepatitis B virus (HBV) protects from HDV infection, but there is no specific vaccine against HDV available for HBsAg-positive individuals. Treatment options for hepatitis delta patients are limited. So far, only interferon-alpha has shown an antiviral efficacy against HDV. Recent trials showed sustained virological response rates concerning HDV in 25%-30% of patients treated with pegylated interferons. HDV is dominant over HBV in the majority of cases, but HBV DNA-positive subjects should be treated with HBV polymerase inhibitors. Combination therapy of pegylated interferon-alpha and adefovir showed a more pronounced HBsAg decline, but the exact role of combination therapies in hepatitis delta requires further investigation. Alternative future treatment strategies may include prenylation inhibitors and HBV entry inhibitors, which are in early clinical development.

Clinical Features of Hepatitis D

Hepatitis D is caused by infection with hepatitis D virus (HDV), a defective RNA virus that requires the obligatory helper function of hepatitis B virus (HBV) for its in vivo transmission. Thus, HDV is acquired only by coinfection with HBV or by superinfection of an HBV carrier. The clinical outcome of hepatitis D differs according to the modality of infection. Whereas coinfection evolves to chronicity in only 2% of the cases, superinfection results in chronic infection in over 90% of the cases. HDV is a highly pathogenic virus that causes acute, often fulminant hepatitis, as well as a rapidly progressive form of chronic viral hepatitis, leading to cirrhosis in 70 to 80% of the cases. The clinical picture of HDV disease is evolving as a consequence of a significant change in the epidemiology of HDV infection, which has led to a significant decline in incidence in Western countries, mainly as a result of universal HBV vaccination programs. However, in the face of a declining prevalence in areas of old endemicity like Europe, immigration poses a threat of HDV resurgence. The interaction of HDV with other hepatitis viruses or human immunodeficiency virus is complex and may lead to different patterns in terms of virologic expression and immunologic responses. Multiple viral infections are associated with rapid progression of liver fibrosis and eventually with the development of hepatocellular carcinoma. Hepatitis D is not a vanishing disease, and continuous efforts should be made to improve its prevention and treatment.