Elebsiran and pegylated-IFNα: Progress toward a functional cure for chronic hepatitis B.

EASL Clinical Practice Guidelines: Management of hepatitis C virus infection

Long-term Therapy With Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B for up to 5 Years

The article entitled Perihepatic lymphadenopathy in children with chronic viral hepatitis(1) is an original paper of high clinical relevance – viral hepatitis B and C are the main causes of chronic hepatitis and liver cirrhosis in children. Based on ultrasound findings, the authors assessed the presence of the perihepatic lymph nodes and their morphology in 49 children with chronic viral hepatitis B and C (38 and 11 children, respectively). The authors hoped that this investigation would help establish a new, non-invasive marker enabling screening examinations to be conducted in children with chronic viral hepatitis. In adults, a correlation was found between the activity of hepatitis and the morphology of the lymph nodes in a US examination, but such a correlation has, until now, not been reported in children(2–4). The results of the study have a clinically significant aspect – the loops of the hepatoduodenal ligament are relatively readily available in a transabdominal examination, and ultrasonography is an inexpensive and safe method to be conducted in children. The authors assumed that the lymph nodes with the size of over 14 mm in the long axis were pathologically enlarged. In a US examination, such nodes were visualized in 70% of children with viral hepatitis and in 11% of healthy children. Based on the studies conducted, it was concluded that the general volume of the perihepatic lymph nodes is greater in children with chronic hepatitis in a statistically significant way (p < 0.05), compared to healthy children: 1.0 ± 1.2 mL (0.1–5.4 mL) vs 0.1 ± 0.1 mL (0.0–0.4 mL). Ultrasonography demonstrated a moderate level of sensitivity (70%) and NPV (75%), and considerable specificity (89%) and PPV (86%) in detecting enlarged perihepatic lymph nodes in children with chronic viral hepatitis. Enlarged lymph nodes of the hepatoduodenal ligament were present in patients with both chronic hepatitis B and C. There were no significant differences in the sensitivity and specificity levels of ultrasonography between the two types of hepatitis (hepatitis B: sensitivity 69%, specificity 89%; hepatitis C: sensitivity 70%, specificity 89%), but the method was characterized by superior accuracy in confirming hepatitis B (PPV 83%) compared to hepatitis C (PPV merely 58%). However, ruling out chronic viral hepatitis based on US findings was much more accurate in children with hepatitis C than in children with hepatitis B (NPV 93% vs 79%). The article summarized above is a very good example of research methodology, particularly for young scientists. The design is exemplary: the study is prospective, randomized; the inclusion and exclusion criteria are clearly specified. The methods involve the principles of so-called good clinical practice. The accurate assessment of the repeatability of size and volume measurements in a US examination must be emphasized. The evidence for a high repeatability of the measurements is an additional argument for including the perihepatic lymph node assessment into everyday clinical practice involving the treatment of children with chronic viral hepatitis B and C. In the Discussion, the authors prove how innovative their results are and indicate the path for further research – the possibility of monitoring the therapy of chronic viral hepatitis using size measurements of the perihepatic lymph nodes. Moreover, the authors also mention other methods enabling perihepatic lymph node imaging, such as CT and MRI. However, the argument concerning limited possibilities of the lymph node reconstruction in the age of multi-slice CT seems unconvincing. Furthermore, the methods of conducting US examinations applied by the authors seem lacking: the authors used a 3.5 MHz transducer in all patients irrespective of their age (1–17). Yet our experience and literature guidelines suggest that probes of higher frequency should be used for the assessment of visceral lymph nodes in younger children. The results of the measurements of the size and volume of the perihepatic lymph nodes in children with chronic viral hepatitis also raise questions regarding their accurate assessment (configuration of the hilum, blood supply and direction of flow) as well as a possible relationship of these features with the activity of the disease. Further investigations should continue the issues started in this article.

Nitric oxide is a free radical gas molecule which may be implicated in antiviral defense. However, there is no information about its possible role in chronic viral hepatitis B and C. In this study we have analyzed the serum levels of NO2- (as an index of nitric oxide generation) from patients with chronic viral hepatitis B and C and relationship of same with the response to interferon therapy. Serum samples were analysed from 61 patients with chronic hepatitis B, 60 patients with chronic hepatitis C, 11 with chronic liver disease of nonviral origin, and 23 healthy controls. Levels of NO2- were statistically higher in healthy controls (P < 0.001) than in patients with chronic liver disease. No relation was found between NO2- and viremia or response to interferon therapy in patients with chronic hepatitis B. In contrast in chronic hepatitis C, responder patients had significantly higher NO2- than nonresponders (P < 0.01). With respect to the relation between NO2- levels and liver damage, patients with cirrhosis had lower NO2- levels than the rest of the patients (P < 0.001). In conclusion, patients with chronic viral hepatitis have low serum NO2- levels.

Chronic hepatitis: Disease factors at diagnosis predictive of mortality

The molecular basis of the failed immune response in chronic HBV: Therapeutic implications

C-reactive protein (CRP) is a liver-specific acute-phase protein, and its expression in hepatocyte is regulated by cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha. Although several alterations in cytokines have been found in patients with chronic viral hepatitis, it remains obscure how CRP expression is associated with progression of the disease in chronic viral infection. In the present study, CRP expression was evaluated in 45 patients with chronic hepatitis B and in 38 patients with chronic hepatitis C. By the immunohistochemical analysis, the intensity of CRP expression in hepatocyte was closely associated with the histology activity index (HAI) score in chronic hepatitis B. In contrast, the association was not found in chronic hepatitis C. When serial changes in serum levels of CRP were compared in long-term follow-up patients including 5 patients with chronic hepatitis B and 4 patients with chronic hepatitis C, serum levels of CRP fluctuated simultaneously with serum levels of alanine aminotransferase in chronic hepatitis B, whereas the correlation was not recognized in chronic hepatitis C. These results suggest that CRP expression correlates with progression of the disease in chronic hepatitis B, but not in chronic hepatitis C. It is also possible that cytokine-mediated response is more pronounced in chronic hepatitis B than in chronic hepatitis C.

Survival data from 379 patients with chronic hepatitis B were analyzed to determine life expectancy for the patient from the time of first contact. One hundred twenty-one patients had chronic persistent hepatitis, 128 had chronic active hepatitis, and 130 had chronic active hepatitis with cirrhosis. The frequency of symptoms (p less than 0.001), stigmata of chronic liver disease (p less than 0.001), and liver function test abnormalities (p less than 0.001) increased as the histologic features worsened, whereas the percentage of patients with circulating hepatitis B DNA polymerase declined (p less than 0.001). Women were uncommon in our series and had less severe disease than men (p less than 0.02). Fifty-one patients had died by the time of this analysis. The estimated 5-year survival rates were 97% for patients with chronic persistent hepatitis, 86% for those with chronic active hepatitis, and 55% for those with chronic active hepatitis with cirrhosis. The usual cause of death was liver failure and its sequelae. A multivariate analysis found age of 40 years or more, total bilirubin level of 1.5 mg/dL or more, ascites, and spider nevi to be factors that identified patients at a higher risk of death. The prognosis for patients with chronic hepatitis B is similar to that for patients with chronic hepatitis of other causes.

IntroductionThe estimation of liver fibrosis in patients chronically infected with hepatitis B or C is crucial in determining the prognosis, surveillance, and treatment decisions. Liver biopsy is still the gold-standard...

Genomic instability in chronic viral hepatitis and hepatocellular carcinoma

Transforming growth factor (TGF)-beta 1 is an important cytokine involved in the pathobiology of tissue fibrosis through its stimulation of the production of, and inhibition of the degradation of, extracellular matrix proteins. We examined the clinical usefulness of plasma TGF-beta 1 concentration as a marker of fibrogenesis in patients with chronic viral hepatitis. Thirty-five patients, 11 with minimal chronic hepatitis, 14 with mild chronic hepatitis and 10 with moderate chronic hepatitis and 20 healthy subjects were studied. Transforming growth factor-beta 1 concentrations in platelet-poor plasma were measured with a TGF-beta 1 enzyme-linked immunosorbent assay system kit after acid-ethanol extraction. Plasma TGF-beta 1 levels were significantly elevated in patients with mild and moderate chronic hepatitis, but not in those with minimal chronic hepatitis, compared with the levels in the controls. Plasma TGF-beta 1 levels were increased in parallel with the histological degree of necroinflammation and of liver fibrosis. Plasma TGF-beta 1 levels were positively correlated with blood levels of procollagen type III N-peptide, and 7S fragment and central triple-helix of type IV collagen. These results suggest that plasma TGF-beta 1 level is a useful marker in assessing the situation of liver active fibrogenesis in patients with chronic viral hepatitis.

Objective. To analyze the effectiveness of etiotropic antiviral therapy with direct antiviral drugs against chronic viral hepatitis C in the adult population of the Perm Krai.&#x0D; Materials and methods. In the regional register of Perm Krai, 20095 patients with chronic viral hepatitis C were registered. In 2019–2021, antiviral therapy with direct antiviral drugs, registered in the Russian Federation, and included in the list of vital and essential medicines for medical use was prescribed to 282 patients with chronic hepatitis C. There were 137 men (48.6 %), 145 (51.4 %) – women. The age of the patients ranged from 26 to 82 years, the duration of the disease – from 3 to 25 years.&#x0D; Results. All the therapy regimes we used showed 100 % effectiveness in the population of patients suffering from chronic hepatitis C associated with mild liver fibrosis regardless of genotype, whereas in the population of patients with grade 3 fibrosis or liver cirrhosis, 100 % effectiveness was achieved only after the use of sofosbuvir-containing schemes. The pangenotypic schemes resulted in 100 % achievement of a stable virological response among patients with genotype 1 regardless of the stage of liver fibrosis and previous therapy experience. In the treatment of patients infected with genotype 3 of hepatitis C virus with severe fibrosis, the effectiveness of 100 % was noted after the use of sofosbuvir-containing regimes.&#x0D; Conclusions. Among the adult population of Perm Krai, the overall effectiveness of therapy in patients with chronic hepatitis C, who used direct antiviral drugs, was 97.8 %.

The presence of autoantibodies is frequent in chronic viral hepatitis evolution. Defining the role of autoimmunity in disease evolution or response to interferon treatment is still in debate, both in children and in adults. There are few studies about the influence of autoimmunity in children with chronic viral hepatitis. The aim of our study was to establish the clinical significance of antinuclear autoantibodies (ANA) in chronic hepatitis B in children. We have studied 80 children with chronic hepatitis B (30 female; mean age 12.31 +/- 4.13 years). For each patient we performed haematological and biochemical tests and in 41 patients we analyzed the liver histology. The immunological parameters analyzed were: circulating immune complexes (CIC), complement, and the serum levels of immunoglobulin G, A, and M. We analysed by indirect fluorescence the presence of ANA and other autoantibodies. The response to treatment (hepatoprotectors, interferon and Lamivudine) was established depending on seroconversion to HBeAb and HBsAb. Positive ANA were found at baseline in 15% of the patients and during follow-up in 21.25%. In ANA-positive patients compared to those without autoantibodies we found lower levels of haemoglobin and platelet numbers (p = 0.0245, p = 0.0236, respectively), higher gamma-glutamyl-transferase level (p = 0.040) and higher CIC level (p = 0.0155). During interferon treatment 13.79% of those who initially tested ANA-negative presented ANA, compared to 2.56% in those without interferon (p = 0.042). There was no difference in response to interferon treatment according to the presence of ANA (p = 0.4201). Searching for ANA in children with chronic hepatitis B is a key element in describing the evolution of these patients, especially when considering interferon therapy. Interferon treatment stimulates the development of ANA, but their presence does not influence the response to this particular treatment. The role of autoimmune processes in the evolution and response to treatment of chronic hepatitis B patients remains controversial.

The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. The aim of the present study was to measure the frequencies of the common HFE gene mutations in Moroccan subjects with chronic viral hepatitis B and C and to assess their influence on the progression of liver disease. H63D and C282Y mutations were screened by the polymerase chain reaction followed by restriction fragment length polymorphism analysis in 170 chronic hepatitis B patients, 168 chronic hepatitis C patients, and 200 healthy controls. A very small proportion of patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV; 1.8% and none, respectively) were heterozygous for the C282Y mutation, that is, rates not statistically different from those observed in healthy control (2%, P > 0.05). Similarly, the frequency of the H63D allele was not significantly different between HBV (13.8%) or HCV (14.3%) patients and controls (13.5%, P > 0.05). Multivariate analysis showed that carriers of the H63D mutation infected with HBV are at higher risk to progress towards an advanced liver disease when compared with patients infected with HBV with wild-type (OR = 2.45, 95% CI = 1.07-5.58). In contrast, no association between HFE mutated HCV-infected patients and an increased risk of disease progression was found (OR = 1.24, 95% CI = 0.61-2.50, P = 0.547). In conclusion, in Morocco the frequency of the HFE C282Y allele is very low and H63D mutation carriage occurs in almost 14% of the patients, a rate similar in chronic hepatitis patients and healthy controls. In the case of chronic hepatitis B, the carriage of the H63D variant represents a risk factor of evolution towards a more active disease.

Chronic hepatitis in children after liver transplantation: role of hepatitis C virus and hepatitis G virus infections