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10 pages, 283 KiB

Open AccessArticle

Factors Associated with Spontaneous Clearance of Recently Acquired Hepatitis C Virus among HIV-Positive Men in Brazil

by Rosario Quiroga Ferrufino, Camila Rodrigues, Gerusa Maria Figueiredo, Daniel Gleison, Silvia Yapura, Maria Laura Mariano de Matos, Steven S. Witkin and Maria Cássia Mendes-Correa

Viruses 2023, 15(2), 314; https://doi.org/10.3390/v15020314 - 23 Jan 2023

Cited by 2 | Viewed by 1479

Abstract

Introduction: The objective of the present study was to describe the clinical and epidemiological aspects of recently acquired hepatitis C virus (HCV) infection and the frequency of its spontaneous clearance in a people living with the human immunodeficiency virus (PLWH) cohort. Methods: We [...] Read more.

Introduction: The objective of the present study was to describe the clinical and epidemiological aspects of recently acquired hepatitis C virus (HCV) infection and the frequency of its spontaneous clearance in a people living with the human immunodeficiency virus (PLWH) cohort. Methods: We reviewed the medical records from all PLWH at the human immunodeficiency virus (HIV) outpatient reference clinic affiliated with the University of São Paulo, Brazil, and identified, by immunoassays and RNA-PCR individuals who acquired HCV infection between January 2015 and December 2017. The factors associated with subsequent spontaneous clearance of the infection in this group were identified and analyzed. Results: Among 3143 PLWH individuals, 362 (11.5%) were coinfected with HCV. Forty-eight (13.2%) of these subjects first became HCV-positive between January 2015 and December 2017. Spontaneous HCV clearance was documented in 23 individuals (47.9%). The majority of this latter group were male (83.3%), and the median age was 31 years (23–39). The main risk group for HCV acquisition was men who had sex with men (MSM) (89.5%). In a multivariate analysis, only an elevated CD4+ T lymphocyte count at the time of seroconversion was found to be associated with subsequent HCV clearance (p = 0.025). Conclusions: In HIV-infected individuals in Sao Paulo, Brazil, most cases of recent HCV transmission were by sexual exposure. In PLWH, particularly in MSM, the individual’s CD4+ T lymphocyte count is a determinant of whether an acquired HCV infection will be prolonged or will spontaneously clear. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

18 pages, 2276 KiB

Open AccessArticle

Genetic Diversity and Possible Origins of the Hepatitis B Virus in Siberian Natives

by Victor Manuylov, Vladimir Chulanov, Ludmila Bezuglova, Elena Chub, Anastasia Karlsen, Karen Kyuregyan, Yulia Ostankova, Alexander Semenov, Ludmila Osipova, Tatjana Tallo, Irina Netesova, Artem Tkachuk, Vladimir Gushchin, Sergey Netesov, Lars O. Magnius and Heléne Norder

Viruses 2022, 14(11), 2465; https://doi.org/10.3390/v14112465 - 7 Nov 2022

Cited by 1 | Viewed by 1783

Abstract

A total of 381 hepatitis B virus (HBV) DNA sequences collected from nine groups of Siberian native populations were phylogenetically analyzed along with 179 HBV strains sampled in different urban populations of former western USSR republics and 50 strains from Central Asian republics [...] Read more.

A total of 381 hepatitis B virus (HBV) DNA sequences collected from nine groups of Siberian native populations were phylogenetically analyzed along with 179 HBV strains sampled in different urban populations of former western USSR republics and 50 strains from Central Asian republics and Mongolia. Different HBV subgenotypes predominated in various native Siberian populations. Subgenotype D1 was dominant in Altaian Kazakhs (100%), Tuvans (100%), and Teleuts (100%) of southern Siberia as well as in Dolgans and Nganasans (69%), who inhabit the polar Taimyr Peninsula. D2 was the most prevalent subgenotype in the combined group of Nenets, Komi, and Khants of the northern Yamalo-Nenets Autonomous Region (71%) and in Yakuts (36%) from northeastern Siberia. D3 was the main subgenotype in South Altaians (76%) and Buryats (40%) of southeastern Siberia, and in Chukchi (51%) of the Russian Far East. Subgenotype C2 was found in Taimyr (19%) and Chukchi (27%), while subgenotype A2 was common in Yakuts (33%). In contrast, D2 was dominant (56%) in urban populations of the former western USSR, and D1 (62%) in Central Asian republics and Mongolia. Statistical analysis demonstrated that the studied groups are epidemiologically isolated from each other and might have contracted HBV from different sources during the settlement of Siberia. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

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7 pages, 251 KiB

Open AccessArticle

Assessment of Adherence to Clinical Guidelines in Patients with Chronic Hepatitis B

by Warshan K. Katwaroe, Sylvia M. Brakenhoff, Daniël P. C. van der Spek, Robert J. de Knegt, Laurens A. van Kleef, Robert A. de Man, Adriaan J. P. van der Meer, Milan J. Sonneveld and the ICARUS Study Group

Viruses 2022, 14(10), 2229; https://doi.org/10.3390/v14102229 - 11 Oct 2022

Cited by 1 | Viewed by 1910

Abstract

Background and aims: Adherence to guidelines is associated with improved long-term outcomes in patients with chronic hepatitis B (CHB). We aimed to study the degree of adherence and determinants of non-adherence to management guidelines in a low endemic country. Methods: We reviewed the [...] Read more.

Background and aims: Adherence to guidelines is associated with improved long-term outcomes in patients with chronic hepatitis B (CHB). We aimed to study the degree of adherence and determinants of non-adherence to management guidelines in a low endemic country. Methods: We reviewed the medical records of all CHB patients who visited our outpatient clinic in 2020. Adherence to guidelines was assessed based on predefined criteria based on the EASL guidance, and included the initiation of antiviral therapy when indicated, the optimal choice of antiviral therapy based on comorbidities, an assessment of HAV/HCV/HDV/HIV serostatus, renal function monitoring and enrolment in a HCC surveillance program if indicated. The adherence rates were compared across types of outpatient clinic (dedicated viral hepatitis clinic versus general hepatology clinic). Results: We enrolled 482 patients. Among the 276 patients with an indication for antiviral therapy, 268 (97.1%) received treatment. Among the patients with renal and/or bone disease, 26/29 (89.7%) received the optimal choice of antiviral agent. The assessment of HAV/HCV/HDV/HIV serostatus was performed in 86.1/91.7/94.4/78.4%. Among the 91 patients treated with tenofovir disoproxil, 57 (62.6%) underwent monitoring of renal function. Of the 241 patients with an indication for HCC surveillance, 212 (88.3%) were enrolled in a surveillance program. Clinics dedicated to viral hepatitis had superior adherence rates compared to general hepatology clinics (complete adherence rates 63.6% versus 37.2%, p < 0.001). Conclusions: Follow-up at a dedicated viral hepatitis clinic was associated with superior adherence to management guidelines. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

13 pages, 976 KiB

Open AccessArticle

The Performance of Serum Alpha-Fetoprotein for Detecting Early-Stage Hepatocellular Carcinoma Is Influenced by Antiviral Therapy and Serum Aspartate Aminotransferase: A Study in a Large Cohort of Hepatitis B Virus-Infected Patients

by Xiangjun Qian, Yanna Liu, Fengping Wu, Siyu Zhang, Jiao Gong, Yuemin Nan, Bo Hu, Junhui Chen, Jingmin Zhao, Xiangmei Chen, Weidong Pan, Shuangsuo Dang and Fengmin Lu

Viruses 2022, 14(8), 1669; https://doi.org/10.3390/v14081669 - 29 Jul 2022

Cited by 4 | Viewed by 2287

Abstract

Background and aims: Factors associated with abnormally elevated alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-infected patients remain to be studied. We aimed to identify factors associated with elevated serum AFP in patients with non-hepatocellular carcinoma (HCC) and early-stage HCC and their influences on [...] Read more.

Background and aims: Factors associated with abnormally elevated alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-infected patients remain to be studied. We aimed to identify factors associated with elevated serum AFP in patients with non-hepatocellular carcinoma (HCC) and early-stage HCC and their influences on the performance of AFP for detecting early-stage HCC. Methods: This multicenter, retrospective study was conducted in 4401 patients with chronic HBV infection, including 3680 patients with non-HCC and 721 patients with early-stage HCC. Factors associated with elevated AFP were analyzed. Diagnostic performance of AFP for early-stage HCC were compared among groups through area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: When analyzed by multivariate logistic regression, antiviral therapy was negatively associated with elevated AFP, while hepatitis B e antigen (HBeAg) and aspartate aminotransferase (AST) > 1× upper limit of normal (ULN) were positively associated with elevated AFP both in patients with non-HCC and early-stage HCC (all p < 0.05). The AUCs of AFP for detecting early-stage HCC in patients with antiviral therapy, HBV DNA (−), alanine aminotransferase (ALT) ≤ 1× ULN, and AST ≤ 1× ULN were significantly higher compared to those in non-antiviral therapy, HBV DNA (+), ALT > 1× ULN, and AST > 1× ULN groups, respectively. When categorizing patients into AST ≤ 1× ULN and > 1× ULN, AFP achieved the highest AUCs in patients with AST ≤ 1× ULN regardless of antiviral treatment (AUCs = 0.813 and 0.806, respectively). Furthermore, there were considerable differences in the cut-off values of AFP in detecting early-stage HCC in different subgroups when applying similar sensitivity and specificity. Conclusions: Antiviral therapy and serum AST might be used to help judge and select the specific cut-off values of serum AFP for HCC surveillance in different at-risk populations. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

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14 pages, 3060 KiB

Open AccessArticle

Structure Prediction and Analysis of Hepatitis E Virus Non-Structural Proteins from the Replication and Transcription Machinery by AlphaFold2

by Adeline Goulet, Christian Cambillau, Alain Roussel and Isabelle Imbert

Viruses 2022, 14(7), 1537; https://doi.org/10.3390/v14071537 - 14 Jul 2022

Cited by 9 | Viewed by 2348

Abstract

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in humans globally. Considered for a long while a public health issue only in developing countries, the HEV infection is now a global public health concern. Most human infections are caused [...] Read more.

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in humans globally. Considered for a long while a public health issue only in developing countries, the HEV infection is now a global public health concern. Most human infections are caused by the HEV genotypes 1, 2, 3 and 4 (HEV-1 to HEV-4). Although HEV-3 and HEV-4 can evolve to chronicity in immunocompromised patients, HEV-1 and HEV-2 lead to self-limited infections. HEV has a positive-sense single-stranded RNA genome of ~7.2 kb that is translated into a large pORF1 replicative polyprotein, essential for the viral RNA genome replication and transcription. Unfortunately, the composition and structure of these replicases are still unknown. The recent release of the powerful machine-learning protein structure prediction software AlphaFold2 (AF2) allows us to accurately predict the structure of proteins and their complexes. Here, we used AF2 with the replicase encoded by the polyprotein pORF1 of the human-infecting HEV-3. The boundaries and structures reveal five domains or nonstructural proteins (nsPs): the methyltransferase, Zn-binding domain, macro, helicase, and RNA-dependent RNA polymerase, reliably predicted. Their substrate-binding sites are similar to those observed experimentally for other related viral proteins. Precisely knowing enzyme boundaries and structures is highly valuable to recombinantly produce stable and active proteins and perform structural, functional and inhibition studies. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

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10 pages, 2268 KiB

Open AccessArticle

Characterization of Chronic Hepatitis E Virus Infection in Immunocompetent Rabbits

by Chunnan Liang, Chenyan Zhao, Tianlong Liu, Bo Liu, Zhiguo Liu, Huili Huang, Wei Liu, Minghai Zhao, Nan Xu, Qiong Lu, Jianhui Nie, Li Zhang, Weijin Huang, Ruiping She and Youchun Wang

Viruses 2022, 14(6), 1252; https://doi.org/10.3390/v14061252 - 9 Jun 2022

Cited by 8 | Viewed by 1725

Abstract

Chronic hepatitis E virus (HEV) infection is frequently reported in immunocompromised patients, but has also been increasingly reported in non-immunocompromised individuals. We characterized the course of chronic HEV infection in immunocompetent rabbits. In two independent experiments, 40 specific-pathogen-free rabbits were infected with a [...] Read more.

Chronic hepatitis E virus (HEV) infection is frequently reported in immunocompromised patients, but has also been increasingly reported in non-immunocompromised individuals. We characterized the course of chronic HEV infection in immunocompetent rabbits. In two independent experiments, 40 specific-pathogen-free rabbits were infected with a rabbit HEV genotype 3 strain in serial diluted titers (10⁸ to 10⁴ copies/mL). Serum and fecal samples were collected weekly and were tested for HEV RNA, antigen, anti-HEV and liver enzymes. Rabbits that spontaneously cleared the infection before 10 weeks post-inoculation (wpi) were kept to the end of the study as recovery control. Liver tissues were collected from HEV-infected rabbits at 5, 10 and 26 wpi for histopathological analysis. Nineteen rabbits (47.5%) developed chronic HEV infection with persistent viraemia and fecal HEV shedding for >6 months. Seroconversion to anti-HEV was observed in 84.2% (16/19) of the chronically infected rabbits. Serum levels of aminotransferase were persistently elevated in most of the rabbits. Characterizations of chronic HEV infection in immunocompetent settings could be recapitulated in rabbits, which can serve as a valuable tool for future studies on pathogenesis. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

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12 pages, 2256 KiB

Open AccessArticle

Burden and Trends of Acute Viral Hepatitis in Asia from 1990 to 2019

by Qiao Liu, Min Liu and Jue Liu

Viruses 2022, 14(6), 1180; https://doi.org/10.3390/v14061180 - 28 May 2022

Cited by 7 | Viewed by 2389

Abstract

Asia has a very high burden of acute hepatitis; thus, a comprehensive study of the current burden and long-term trends of acute hepatitis in Asia is needed. We aimed to assess the current status and trends from 1990 to 2019 of acute hepatitis [...] Read more.

Asia has a very high burden of acute hepatitis; thus, a comprehensive study of the current burden and long-term trends of acute hepatitis in Asia is needed. We aimed to assess the current status and trends from 1990 to 2019 of acute hepatitis burden in Asia, using the data from the Global Burden of Diseases Study 2019 (GBD 2019) results. Methods: We used the data from the GBD 2019. Absolute death, incidence, and disability adjusted life years (DALY) number and rate of acute hepatitis in Asia were derived from the database from 1990 to 2019. Age-standardized mortality, incidence and DALY rates (ASMR, ASIR and ASDR) were used to compare populations in different regions and times. The estimated annual percentage change (EAPC) in the rates quantified the trends of the acute hepatitis burden. Results: From 1990 to 2019, the ASMR and ASDR of acute hepatitis decreased significantly at different paces, with the largest decrease in acute hepatitis C and the smallest in acute hepatitis E. The ASIR of acute hepatitis decreased relatively slowly, by an average of 0.06% (95% CI, 0.05–0.08%) per year in acute hepatitis A, 0.91% (0.64–1.18%) per year in acute hepatitis C and 0.26% (0.24–0.28%) per year in acute hepatitis E; while the ASIR of acute hepatitis B decreased by an average of 1.95% (1.08–2.11) per year. From 1990 to 2019, the incidence rate of acute hepatitis A increased in most age groups (from the age of 5 to 70), with the 50–55 years group having the fastest increase by an average of 1.81% (95% CI, 1.67–1.95%) per year. In 2019, Afghanistan had the highest ASMR (10.44 per 100,000) and ASDR (357.85 per 100,000) of acute hepatitis, and the highest ASIR was in Mongolia (4703.14 per 100,000). Conclusions: In Asia, the burden of acute viral hepatitis was at a relatively high level, compared with the other four continents. International cooperation and multifaceted and multisectoral actions are needed for Asian countries to eliminate viral hepatitis and to contribute to the global elimination of viral hepatitis. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

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Review

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18 pages, 752 KiB

Open AccessReview

Endoplasmic Reticulum Stress in Hepatitis B Virus and Hepatitis C Virus Infection

by Tengyue Hu, Jiayi Wang, Weixiu Li, Miao Liu, Ning Han, Man Yuan, Lingyao Du and Hong Tang

Viruses 2022, 14(12), 2630; https://doi.org/10.3390/v14122630 - 25 Nov 2022

Cited by 3 | Viewed by 2236

Abstract

Endoplasmic reticulum (ER) stress, a type of cellular stress, always occurs when unfolded or misfolded proteins accumulating in the ER exceed the protein folding capacity. Because of the demand for rapid viral protein synthesis after viral infection, viral infections become a risk factor [...] Read more.

Endoplasmic reticulum (ER) stress, a type of cellular stress, always occurs when unfolded or misfolded proteins accumulating in the ER exceed the protein folding capacity. Because of the demand for rapid viral protein synthesis after viral infection, viral infections become a risk factor for ER stress. The hepatocyte is a cell with large and well-developed ER, and hepatitis virus infection is widespread in the population, indicating the interaction between hepatitis viruses and ER stress may have significance for managing liver diseases. In this paper, we review the process that is initiated by the hepatocyte through ER stress against HBV and HCV infection and explain how this information can be helpful in the treatment of HBV/HCV-related diseases. Full article

(This article belongs to the Special Issue Acute and Chronic Viral Hepatitis)

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