Antiviral Therapy of Chronic Hepatitis B Virus between Present and Future.

Background/Objectives: The objective of this study was to analyze the results of clinical trials regarding long-term antiviral therapies in chronic hepatitis with HBV to compare current therapeutic protocols and to analyze the results of preliminary studies with new antiviral therapies for HBV. Methods: Clinical studies and meta-analyses from PubMed, Google Scholar, and Research Gate from 2011 to 2024 were analyzed on patients undergoing chronic antiviral therapy for HBV, and a retrospective observational study performed in our clinic on a group of 76 patients undergoing chronic therapy with entecavir was presented. Also, a summary of the results of preliminary studies with various innovative antiviral molecules for HBV was performed. Results: The results of extensive clinical trials reveal that current therapies for chronic HBV are well tolerated and maintain good viral suppression if the patient is adherent to therapy. Innovative therapies aim to eliminate HBsAg and, thus, significantly shorten the duration of treatment, and the preliminary results of the studies are promising. Conclusions: Being an asymptomatic condition that requires life-long therapy, adherence to therapy is a real problem. Also, the risk of decompensation of liver cirrhosis and adenocarcinoma remains important in these patients. Future research is needed to perfect some antiviral therapy schemes that shorten the treatment period but also decrease the rate of progression towards decompensated cirrhosis and liver adenocarcinoma.

Risk of hepatitis B reactivation: From biologic therapies for psoriasis to immunosuppressive therapies for COVID-19 (Review).

The cytokine storm from the evolution of severe cases of COVID-19, requiring strong immunosuppressive therapies, has raised the issue of reactivation of hepatitis B virus (HBV) infections in these patients. An analysis of the first observational studies in patients with COVID-19 and immunosuppressive therapy and HBV infection along with special clinical cases was presented, as well as personal experience on a series of cases (a group of 958 patients with COVID-19), compared with the analysis of studies performed on patients with HBV infection that underwent biological therapies for psoriasis and personal experience (a group of 81 psoriasis patients treated with biological therapies). Clinical studies have revealed that HBV reactivation in patients undergoing biological therapies for psoriasis, can be prevented with monitoring and treatment protocols and thus, these therapies have been demonstrated to be safe and effective. In COVID-19, immunosuppressive therapies are short-lived but in high doses, and the conclusions of clinical trials are contradictory, but there are published cases of HBV reactivation, which requires a unitary attitude in the prevention of HBV reactivation in these patients. An algorithm was presented for monitoring and treatment of HBV infection for patients with psoriasis treated with biological therapy and the conditions when this protocol can be used for patients with COVID-19 and immunosuppressive therapy.

Old and new therapeutic strategies in systemic sclerosis (Review).

Systemic sclerosis (SSc) is a chronic inflammatory disease with autoimmune determinism having an incompletely known pathogenesis. Although not all links in the pathogenic chain are known, studies have shown that vasculopathy is the initial event and is followed by extensive fibrosis of the skin and internal organs. New therapeutic strategies have been developed in recent years, thanks to innovative research which has increased understanding of the disease mechanisms. No curative treatment for SSc is currently known. Therefore, the therapeutic target in SSc is its symptomatology. Peripheral vasculopathy can be improved by administering vasodilators. Endothelin receptor antagonists and 5-phosphodiesterase inhibitors have a double benefit, both on peripheral and on pulmonary vasculopathy. Several molecules with antifibrotic effects are currently available; however, further studies are needed to confirm their beneficial effects. Immunosuppressants manage to control the cutaneous and visceral fibrotic process, thereby remaining as first-line drugs in the treatment of SSc. Although biological therapy using rituximab and tocilizumab has shown promising results in pulmonary fibrosis, ongoing studies are needed to determine their exact impact. The authors have differing views on the triggering role of glucocorticoids and the benefits of angiotensin-converting enzyme inhibitors in renal scleroderma. Some aspects of this disease such as calcinosis and pruritus, asthenia, or joint and muscle damage, remain difficult to manage.

Keratosis pilaris atrophicans faciei: An observational, descriptive, retrospective clinical study.

Keratosis pilaris atrophicans faciei (KPAF) is a hereditary follicular disorder, an atrophicans subtype of keratosis pilaris (KP) with a highly elusive diagnosis. Clinically, it presents with follicular, horny papules surrounded by an erythematous halo of the cheeks, forehead, chin and eyebrows, and it is followed by a gradual hair loss on the lateral margins of the eyebrows. The onset is as early as a few months after birth, but it is mainly diagnosed in children and adolescents and it can persist through adulthood. At present, the natural progression of the disease is poorly understood, which makes a correct diagnosis highly unlikely. The aim of the present study was to describe the clinical characteristics of KPAF in patients encountered in daily practice, in order to find common characteristics that may aid in the earlier recognition of the disease. An observational, descriptive, retrospective study was performed on 14 patients diagnosed with KPAF between January 2000 and December 2020. The mean age at diagnosis was 17.04 years and the onset of clinical symptoms appeared at a mean age of 4.85 years. The first clinical symptom was KP involving either the upper or lower limbs, or both. Then, erythema of the face appeared at a mean age of 7.21 years, keratotic papules on the face at a mean age of 8.35 years and, finally, loss of hair on the lateral margins of the eyebrows at a mean age of 14 years. The patients also had concomitant xerosis cutis, multiple mole syndrome, acne, contact dermatitis and Laugier-Hunziker syndrome. Evidence of disease progression, associations, as well as efficacious treatment measures are lacking. An earlier diagnosis potentially allows for a more efficacious, targeted treatment option. Either topical emollients, systemic retinoids or laser therapy may prove effective for each patient individually.

Predictive value of immunological markers in systemic sclerosis.

Systemic sclerosis (SSc) is a collagenosis characterized by excessive deposition of collagen in the skin and viscera, in a background of immune disorder. The immunological profile of SSc often shows elevated levels of antinuclear antibodies (ANAs). However, many authors have identified cases of SSc having normal ANA levels, framed as paraneoplastic SSc. Among patients with negative ANAs in our group, we did not identify any neoplastic process that could support this hypothesis. The extended detection of autoantibodies is extremely useful in establishing the subset of SSc. Thus, anti-Scl70 antibodies are specific for the diffuse subset of SSc, while anticentromere antibodies (ACAs) have specificity for a limited subset. However, studies have shown the existence of cases of diffuse SSc having high titers of ACAs and cases of limited SSc with high titers of anti-Scl70 antibodies. This indicates an inconsistent association between the disease subset and the autoantibodies specific to each subset. Our study found a more balanced consistency between disease subsets and autoantibodies specific for each subset. Therefore, the percentages of patients having an immunological profile inconsistent with the subset of SSc, are lower than those found by other authors. This observation opens the perspective of larger studies on the immunological profile in SSc.

COVID-19 impact on the liver.

The coronavirus disease 2019 (COVID-19) pandemic imposed arestructuring of global health systems by rethinking spaces used for the care of these patients and the additions of intensive care, infectious diseases and pneumology departments. This paper provides evidence on the presence of severe acute respiratory syndrome coronavirus 2 in hepatocytes and its direct cytopathic activity, as well as the degree of liver damage due to drug toxicity, inflammation and hypoxia in COVID-19. A review of clinical trials has quantified liver damage through both pathology and biochemistry studies. Additionally, we briefly present the results of a study conducted in our clinic on 849 patients admitted for COVID-19 treatment, of which 31 patients had pre-existing chronic liver disease and 388 patients had values above the normal limit for alanine aminotransferase, aspartate aminotransferase, and total bilirubin. It was observed that patients with abnormal liver tests were significantly statistically older, had more comorbidities and had a higher percentage of unfavourable evolution (death or transfer to intensive care). The conclusion of this paper is that the main causes of liver damage are direct viral aggression, coagulation dysfunction and endothelial damage, and patients with impaired liver function develop more severe forms of COVID-19 which requires special care by a multidisciplinary team that includes a hepatologist.

Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade (Review).

Interleukin 6 (IL-6), a cytokine produced by various cells of the human body (macrophages, lymphocytes, astrocytes, ischemic myocytes, endothelial cells) has both pro-inflammatory and anti-inflammatory properties, being a key component in regulating various physiologic and pathological processes. The structure of this molecule and the receptor system it possesses are important due to the different activities that IL-6 can exert; through trans-signaling pro-inflammatory activities are mediated, while through classic signaling, IL-6 is responsible for anti-inflammatory and regenerative activities. IL-6 signaling is involved in coronary artery disease and the global COVID-19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS-CoV-2, and is also associated with smoking or obesity-classic cardiovascular risk factors which promote inflammatory states. IL-6 levels are proportionally correlated with dyslipidemia, hypertension and glucose dysregulation, and they are associated with poor outcomes in patients with unstable angina or acute myocardial infarction. IL-6 targeting for treatment development (not only) in cardiovascular disease and COVID-19 is still a matter of ongoing research, although tocilizumab has proven to be effective in reducing the proatherogenic effects of IL-6 and is suggested to improve COVID-19 patient survival.

Epidemiological profile of systemic sclerosis in the southeast region of Romania.

Systemic sclerosis (SSc) is a collagenosis, in which the microvasculature of the skin and internal organs becomes affected, followed by excessive deposition of connective tissue. It has been included in the group of rare diseases, and it seems to have had an increasing incidence over the last two decades. Statistics show, not only an increase in the incidence of SSc, but that of autoimmune diseases as a whole. The present study aimed to outline the epidemiological profile of SSc in the southeast region of Romania and to identify similarities and differences concerning the epidemiology of this disease in other countries. The current observational study was carried out on a group of 22 patients who were diagnosed with SSc and who were hospitalized at a university clinic in Bucharest. Our research revealed a higher prevalence of women suffering from SSc, with higher numbers suffering from the diffuse subset of this disease. In addition, we found that the majority of patients came from urban areas. SSc has an important impact on the quality of life of patients, thus opening the opportunity for studies to be carried out on larger populations of patients in order to identify epidemiological similarities and differences in various countries, as well as finding new experimental models useful for future research.

Etiological factors of systemic sclerosis in the southeast region of Romania.

Systemic sclerosis (SSc) is a relatively rare autoimmune disease with skin and visceral involvement, having a yet unknown etiopathogenesis. Research has shown that professional exposure to various polluting chemicals such as dyes, aliphatic and aromatic organic solvents, inhalable silica dust or certain heavy metals, can be triggering factors for this disease when they overlap a predisposing genetic profile. Smoking is still a debated factor involved in the etiology of SSc, as authors have divergent opinions on this matter. The present study was designed to analyze the etiological factors identified in the group of 37 patients with diffuse and limited SSc from the southeast region of Romania and the results were compared to the literature data. In the group of patients included in this study, occupational exposure and smoking history were not present in all patients, and a hereditary factor was identified only in an isolated case. The majority of patients suffered from a major negative psychological event or from long-term stressful situations and these factors were associated with smoking history or occupational exposure; this suggests that SSc is initiated in a set of cumulative triggering factors.

Perspectives on skin disorder diagnosis among people living with HIV in southeastern Romania.

The beginnings of the human immunodeficiency virus (HIV) pandemic are closely linked to dermatological conditions. A large part of the population living with HIV (PLWH) has a series of skin conditions that determine at some point, a visit to the dermatologist. The introduction of highly active antiretroviral therapy (HAART) more than 20 years ago has diminished the range of dermatological conditions, with improved immunosuppression of CD4 lymphocytes. The study aimed to describe the prevalence of the diagnosed type of skin changes in PLWH receiving antiretroviral therapy and their stratification according to the degree of immunodeficiency. A prospective study was conducted on 57 PLWH evaluated monthly at an HIV outpatient clinic, from a tertiary hospital in southeastern Romania. Clinical examination and dermoscopy revealed the existence of a wide range of dermatological conditions; all 57 patients (100%) being diagnosed with one or more dermatological conditions. As our study shows, the prevalence of different dermatoses among PLWH varies depending on the geographical region. At the same time, under HAART, the image of dermatoses associated with decreased immunity from HIV infection has changed. The skin changes of PLWH no longer fully follow the classical staging, based on the degree of immunosuppression.

Influence of phytochemicals in induced psoriasis (Review).

Cytokines involved in pathogenesis of psoriasis such as interleukins (IL-1ß, IL-6, IL-17, IL-22, IL-23), interferon-α, tumor necrosis factor-α and interferon-γ can also become therapeutic targets. Research currently uses murine models of imiquimod-induced psoriatic-type dermatitis in order to analyze potentially helpful phytotherapeutics for psoriasis treatment: Curcuma longa, Aloe vera, Nigella sativa, Rubia cordifolia, Smilax china, Thespesia populnea, Wrightia tinctoria, Scutellaria baicalensis, Cassia tora, Pongamia pinnata and various Chinese herbal formulas. Psoriasis is a chronic inflammatory disease with complex pathogenic mechanisms that yield abnormal immune responses with clinical and morphological echoes (erythematous, scaly plaques with a histopathological basis made up of alterations i.e. keratinocyte aberrant proliferation, parakeratosis or chronic inflammation). The current therapeutic approach has only been able to manage the disease, without ensuring a certified treatment, thus giving rise to the need for better medications. This novel therapeutic approach has shown promising results in preclinical studies, giving hope for future phytochemical animal-based studies.

Acyclovir-induced immune thrombocytopenia: Case report and review of the literature.

There are a number of medications which can serve as catalysts for drug-induced immune thrombocytopenia (DIPT). A minimum of six different mechanisms have been put forward as the means by which drug-induced antibodies can encourage platelet destruction, thus emphasising the complexity of the pathogenesis of DITP. Acyclovir, has been widely used because of its highly potent prohibitive properties for infections caused by HSV and VZV. The common adverse effects of this drug are well known, the severe adverse reactions are mostly related to high dose intravenous administrations. The immune thrombocytopenia induced by acyclovir is unusual. The authors present a rare clinical case of acyclovir-induced immune thrombocytopenia in a 72-year-old female patient with typical herpes zoster treated with acyclovir. The clinical and laboratory findings, taken together with the transitory relationship between acycolvir and the start of thrombocytopenia, combined with the elimination of the other know sources of thrombocytopenia, allowed us to reach the diagnosis of acyclovir-induced immune thrombocytopenia. An international database search was employed to complete an extensive review of the current literature. Contemporary information on acyclovir-induced immune thrombocytopenia was collected by the analysis of present day review articles and accessible case reports. The authors found five published cases of acyclovir-induced immune thrombocytopenia. Analyzing these articles it was concluded that immune thrombocytopenia induced by acyclovir is rare, and an unusual side effect, with good prognosis. Prompt diagnosis is vital to appropriate management, therefore clinicians need to be cognisant of this rare potential adverse reaction.