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Chronic Hepatitis C: Pathophysiology and Clinical Issues
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Chronic Hepatitis C: Pathophysiology and Clinical Issues

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 20822

Special Issue Editors

Dr. Maria Lorena Abate

E-Mail Website
Guest Editor
Department of Medical Sciences, University of Turin, 10100 Turin, Italy
Interests: genetic polymorphisms; viral genotypes; gene expression; chronic viral hepatitis; HCV; HBV; liver fibrosis; cirrhosis; hepatocellular carcinoma biomarkers; non-invasive assessment
Dr. Gian Paolo Caviglia

E-Mail Website
Guest Editor
Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Interests: biomarkers; cirrhosis; hepatitis B virus; hepatocellular carcinoma; hepatitis D virus; inflammatory bowel disease; liver fibrosis; non-alcoholic fatty liver disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Globally, it is estimated that 71 million people are chronically infected with hepatitis C virus (HCV). The natural history of chronic hepatitis C (CHC) is characterized by a persistent hepatic inflammation that progressively leads to fibrosis accumulation and over time to cirrhosis—the principal risk factor for hepatocellular carcinoma (HCC) development. Until 2011, the standard of care for CHC was dual therapy based on the time-honored pegylated interferon in combination with ribavirin, resulting in rates of sustained virologic response (SVR) ranging from 40% to 80% according to HCV genotypes. Thereafter, the approval of the first generation of protease inhibitors, followed by the second generation of therapeutic agents with direct antiviral activity against HCV (direct-acting antivirals, DAAs) represented a pivotal change for the treatment of CHC; these drugs achieved very high rates of SVR (>90%), improved tolerability, and reduced treatment duration. Now, the elimination of HCV by 2030 proposed by the WHO appears more feasible.

However, there are still some major biological and clinical aspects related to chronic HCV infection that deserve further study, including but not limited to the residual risk of liver cirrhosis complications in patients successfully treated with DAAs, the effect of comorbidities on SVR, the possible role and clinical significance of occult HCV infection, extrahepatic manifestations of chronic HCV infection, and HCV vaccination.

For this Special issue, we encourage the submission of manuscripts on any aspects of chronic HCV infection, from basic to clinical and translational research.

Dr. Maria Lorena Abate
Dr. Gian Paolo Caviglia
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Hepatitis C Virus
  • Liver fibrosis
  • Cirrhosis
  • Hepatocellular carcinoma
  • Co-infection
  • Biomarkers
  • B-cell response
  • T-cell response
  • Antiviral therapy
  • Extra-hepatic manifestations

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Published Papers (8 papers)

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Editorial

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3 pages, 207 KiB  
Editorial
Chronic Hepatitis C: Pathophysiology and Clinical Issues
by Maria Lorena Abate and Gian Paolo Caviglia
Biology 2022, 11(12), 1737; https://doi.org/10.3390/biology11121737 - 29 Nov 2022
Cited by 1 | Viewed by 2371
Abstract
Globally, it is estimated that 56 [...] Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)

Research

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8 pages, 639 KiB  
Communication
Changes in Liver Stiffness and Markers of Liver Synthesis and Portal Hypertension following Hepatitis C Virus Eradication in Cirrhotic Individuals
by Angelo Armandi, Chiara Rosso, Giulia Troshina, Nuria Pérez Diaz Del Campo, Chiara Marinoni, Aurora Nicolosi, Gian Paolo Caviglia, Giorgio Maria Saracco, Elisabetta Bugianesi and Alessia Ciancio
Biology 2022, 11(8), 1160; https://doi.org/10.3390/biology11081160 - 2 Aug 2022
Cited by 4 | Viewed by 1785
Abstract
The advent of direct antiviral agents (DAAs) has radically changed the natural history of hepatitis C virus (HCV) chronic liver disease. Even patients with cirrhosis may display improvements in liver function or features of portal hypertension following viral eradication. The aim of this [...] Read more.
The advent of direct antiviral agents (DAAs) has radically changed the natural history of hepatitis C virus (HCV) chronic liver disease. Even patients with cirrhosis may display improvements in liver function or features of portal hypertension following viral eradication. The aim of this study was to assess whether a HCV cure would lead to improvements in cirrhotic patients using simple, readily available tools in clinical practice, together with liver stiffness (LS) measurement. This is a retrospective study of cirrhotic patients with cured HCV infection, with or without previous decompensation. Clinical and biochemical parameters as well as LS measurements were collected before antiviral treatment with DAAs and after 6 months following sustained virological response. Hepatic synthesis was assessed by serum albumin levels. Portal hypertension was indirectly assessed by platelet count. Liver function was determined by the CHILD score. A total of 373 cirrhotic patients with successful HCV eradication were retrospectively included. After 6 months of follow-up, a significantly higher proportion of patients showed improved liver function, shifting from the CHILD B/C to CHILD A group, (71.4%, p < 0.001). Similarly, LS improved from a median of 19.3 kPa (14.7–27) at the baseline vs. a median of 11.6 (7.7–16.8 kPa) at follow-up (p < 0.001). The proportion of patients who showed improved hepatic synthesis was 66.0%, which was statistically different when compared to that of patients who had a worsened condition (0.3%) (p < 0.001). Moreover, when classifying the cohort according to the RESIST-HCV score, we found that a significant proportion of patients shifted into the “low risk” group following DAA treatment (52% baseline vs. 45.6% at follow-up, p = 0.004). Even in the decompensated patients, LS improved from 1.6 to 2-fold from the baseline. Antiviral treatment is effective in improving indirect signs of hepatic synthesis and portal hypertension. Similarly, the LS values displayed significant improvements, even in decompensated patients. Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)
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12 pages, 645 KiB  
Article
Telemedicine Improves HCV Elimination among Italian People Who Use Drugs: An Innovative Therapeutic Model to Increase the Adherence to Treatment into Addiction Care Centers Evaluated before and during the COVID-19 Pandemic
by Valerio Rosato, Riccardo Nevola, Vincenza Conturso, Pasquale Perillo, Davide Mastrocinque, Annalisa Pappalardo, Teresa Le Pera, Ferdinando Del Vecchio and Ernesto Claar
Biology 2022, 11(6), 800; https://doi.org/10.3390/biology11060800 - 24 May 2022
Cited by 7 | Viewed by 2187
Abstract
People who use drugs (PWUDs) are generally considered “hard-to-treat” patients, due to adherence to HCV antiviral therapy or re-infection concerns. Linkage-to-care still remains a significant gap for HCV elimination, worsened by the COVID-19 pandemic. To reduce time-to-treat and improve treatment adherence, we have [...] Read more.
People who use drugs (PWUDs) are generally considered “hard-to-treat” patients, due to adherence to HCV antiviral therapy or re-infection concerns. Linkage-to-care still remains a significant gap for HCV elimination, worsened by the COVID-19 pandemic. To reduce time-to-treat and improve treatment adherence, we have developed a patient-tailored model-of-care, decentralized within the addiction center and supervised remotely by hepatologists. From January 2017 to December 2020, patients were enrolled in one addiction care center in Southern Italy, where a complete hepatologic assessment, including blood chemistry, ultrasound, and transient elastography examination, was provided. DAAs treatment has been adapted on clinical features, also performing a daily administration during an outpatient visit, and monitored remotely by specialists via telemedicine interactions. Adherence was evaluated on the accomplishment of therapy or on the percentage of attended visits. From a total of 690 PWUDs, 135 had an active HCV infection and were enrolled in the study. All patients started the treatment within 3 weeks after HCV diagnosis. Six drop-outs were recorded, obtaining a sustained virological response at week 12 (SVR12) in 98.5% of PWUDs. There were only two cases of treatment failure, one of which is re-infection. No differences were found between the SVR12 rates before and during the COVID-19 pandemic. We obtained a high SVR12 rate, providing a comprehensive assessment within the addiction care center, tailoring the drug administration with a hepatologic remote stewardship. Our therapeutic model should improve the time-to-treat and treatment adherence in PWUDs. Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)
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12 pages, 2087 KiB  
Article
Epidemiology of HCV and HBV in a High Endemic Area of Southern Italy: Opportunities from the COVID-19 Pandemic—Standardized National Screening or One Tailored to Local Epidemiology?
by Riccardo Nevola, Vincenzo Messina, Aldo Marrone, Nicola Coppola, Carolina Rescigno, Vincenzo Esposito, Vincenzo Sangiovanni, Ernesto Claar, Mariantonietta Pisaturo, Francesco Maria Fusco, Pietro Rosario, Antonio Izzi, Raffaella Pisapia, Valerio Rosato, Paolo Maggi and Luigi Elio Adinolfi
Biology 2022, 11(4), 609; https://doi.org/10.3390/biology11040609 - 16 Apr 2022
Cited by 7 | Viewed by 2480
Abstract
The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV [...] Read more.
The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV and HBV markers and the ability of current screening program to capture cases. We evaluated 2126 hospitalized patients in seven COVID Centers of Naples and Caserta area in which 70% of the Campania population lives. HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively, with no differences between gender. Decade distribution for birth year shows a bimodal trend of HCV prevalence, with a peak (11.6%) in the decade 1930–1939 and a second peak (5.6%) for those born in 1960–1969. An analysis of the screening period imposed by the Italian government for those born between 1969 and 1989 shows that only 17% of cases of HCV infection could be captured. A small alignment of the screening period, i.e., those born from 1960 to 1984, would capture 40% of cases. The data confirm the high endemicity of our geographical area for hepatitis virus infections and underline the need for a tailored screening program according to the regional epidemiology. Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)
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15 pages, 1383 KiB  
Article
Human Herpesviruses Increase the Severity of Hepatitis
by Kirill I. Yurlov, Olga V. Masalova, Lidiia B. Kisteneva, Irina N. Khlopova, Evgeny I. Samokhvalov, Valentina V. Malinovskaya, Vladimir V. Parfyonov, Alexander N. Shuvalov and Alla A. Kushch
Biology 2021, 10(6), 483; https://doi.org/10.3390/biology10060483 - 29 May 2021
Cited by 7 | Viewed by 3292
Abstract
Acute and chronic liver diseases are a major global public health problem; nevertheless, the etiology of 12–30% of cases remains obscure. The purpose of this research was to study the incidence of human herpesviruses (HHVs) cytomegalovirus, Epstein–Barr virus (EBV), and HHV-6 in patients [...] Read more.
Acute and chronic liver diseases are a major global public health problem; nevertheless, the etiology of 12–30% of cases remains obscure. The purpose of this research was to study the incidence of human herpesviruses (HHVs) cytomegalovirus, Epstein–Barr virus (EBV), and HHV-6 in patients with hepatitis and to examine the effect of HHV on the disease severity. We studied the clinical materials of 259 patients with hepatitis treated in Infectious Clinic n.1 (Moscow) and the archived materials of 118 patients with hepatitis C. HHV DNA was detected in the whole blood in 13.5% of patients with hepatitis B or C and in 10.1% of patients with hepatitis of unspecified etiology. EBV demonstrated the highest incidence (58.1%). Cirrhosis was diagnosed in 50% of patients with HHV and in 15.6% of patients without HHV. In patients with hepatitis C, the frequency of HHV was higher in liver biopsy (38.7%) compared to blood. The clinical and virological indicators of hepatitis were considerably higher in patients with coinfection. Conclusion: HHV detected in patients with viral hepatitis has been associated with a significant effect on the severity of the disease, and we suggest monitoring HHV DNA in patients with severe hepatitis and/or poor response to antiviral drugs. Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)
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9 pages, 3743 KiB  
Article
The Clinical Role of Serum Epidermal Growth Factor Receptor 3 in Hepatitis C Virus-Infected Patients with Early Hepatocellular Carcinoma
by Gian Paolo Caviglia, Maria Lorena Abate, Emanuela Rolle, Patrizia Carucci, Angelo Armandi, Chiara Rosso, Antonella Olivero, Davide Giuseppe Ribaldone, Francesco Tandoi, Giorgio Maria Saracco, Alessia Ciancio, Elisabetta Bugianesi and Silvia Gaia
Biology 2021, 10(3), 215; https://doi.org/10.3390/biology10030215 - 11 Mar 2021
Cited by 5 | Viewed by 2235
Abstract
Epidermal growth factor receptor 3 (ERBB3) is a surface tyrosine kinase receptor belonging to the EGFR/ERBB family, involved in tumor development and progression. We evaluated the diagnostic and prognostic value of serum ERBB3 measurement in hepatitis C virus (HCV)-infected patients with early hepatocellular [...] Read more.
Epidermal growth factor receptor 3 (ERBB3) is a surface tyrosine kinase receptor belonging to the EGFR/ERBB family, involved in tumor development and progression. We evaluated the diagnostic and prognostic value of serum ERBB3 measurement in hepatitis C virus (HCV)-infected patients with early hepatocellular carcinoma (HCC). A total of 164 HCV-infected patients (82 with cirrhosis and 82 with early HCC) were included in the study. HCC was classified according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Among patients with HCC, 23 (28%) had a diagnosis of very early tumor (BCLC = 0), while 59 (62%) had a diagnosis of early HCC (BCLC = A). Median overall survival (OS) in patients with HCC was 79.2 (95% CI 51.6–124.8) months. While ERBB3 serum values were similar between patients with cirrhosis and those with HCC (p = 0.993), in the latter, serum ERBB3 ≥ 2860 RU resulted significantly and independently associated with OS (Hazard Ratio = 2.24, 95% CI 1.16–4.35, p = 0.017). Consistently, the 1-, 3-, and 5-year OS rates in patients with serum ERBB3 ≥ 2860 RU were 90% (36/40), 53% (19/36), and 28% (8/29) in comparison to patients with serum ERBB3 < 2860 RU, which were 98% (40/41), 80% (32/40), and 74% (26/35) (Log-rank test; p = 0.014). In conclusion, serum ERBB3 values resulted an independent prognostic factor of patients with early HCC and might be useful to tailor more personalized treatment strategies. Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)
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Review

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14 pages, 700 KiB  
Review
Can Telemedicine Optimize the HCV Care Cascade in People Who Use Drugs? Features of an Innovative Decentralization Model and Comparison with Other Micro-Elimination Strategies
by Riccardo Nevola, Valerio Rosato, Vincenza Conturso, Pasquale Perillo, Teresa Le Pera, Ferdinando Del Vecchio, Davide Mastrocinque, Annalisa Pappalardo, Simona Imbriani, Augusto Delle Femine, Alessia Piacevole and Ernesto Claar
Biology 2022, 11(6), 805; https://doi.org/10.3390/biology11060805 - 24 May 2022
Cited by 4 | Viewed by 2387
Abstract
People who use drugs (PWUDs) are a crucial population in the global fight against viral hepatitis. The difficulties in linkage to care, the low adherence to therapy, the frequent loss to follow-up and the high risk of re-infection make the eradication process of [...] Read more.
People who use drugs (PWUDs) are a crucial population in the global fight against viral hepatitis. The difficulties in linkage to care, the low adherence to therapy, the frequent loss to follow-up and the high risk of re-infection make the eradication process of the hepatitis C virus (HCV) really hard in this viral reservoir. Several management and treatment models have been tested with the aim of optimizing the HCV care cascade in PWUDs. Models of decentralization of the care process and integration of services seem to provide the highest success rates. Giving this, telemedicine could favor the decentralization of diagnostic-therapeutic management, key for the implementation of linkage to care, reduction of waiting times, optimization of adherence and results and reduction of the costs. The purpose of this literature review is to examine the role and possible impact of telemedicine in optimizing the HCV care cascade, comparing the different care models that have shown to improve the linkage to care and therapeutic adherence in this special population. Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)
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11 pages, 306 KiB  
Review
Autoantibodies and Rheumatologic Manifestations in Hepatitis C Virus Infection
by Marta Priora, Richard Borrelli, Simone Parisi, Maria Chiara Ditto, Cristina Realmuto, Angela Laganà, Chiara Centanaro Di Vittorio, Rosanna Degiovanni, Clara Lisa Peroni and Enrico Fusaro
Biology 2021, 10(11), 1071; https://doi.org/10.3390/biology10111071 - 20 Oct 2021
Cited by 9 | Viewed by 2794
Abstract
HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, [...] Read more.
HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, the high frequency of rheumatoid factor (45–70%), antinuclear (10–40%) and anticardiolipin (15–20%) antibodies is a B-cell mediated finding sustained by the infection. However, the possibility that a primitive rheumatic pathology may coexist with the HCV infection is not to be excluded thus complicating a differential diagnosis between primitive and HCV-related disorders. Full article
(This article belongs to the Special Issue Chronic Hepatitis C: Pathophysiology and Clinical Issues)
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