scholarly journals A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 969 ◽  
Author(s):  
Pesavento ◽  
Jackson ◽  
Hampson ◽  
Munday ◽  
Barrs ◽  
...  

In 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV). A novel hepatitis B-like virus has recently been identified in domestic cats. The pathogenic potential of domestic cat hepadnavirus (DCH), for which 6.5% to 10.8% of pet cats are viremic, is unknown. We evaluated stored formalin-fixed, paraffin-embedded biopsies of diseased and normal feline liver for the presence of DCH using PCR and in situ hybridization (ISH). DCH was detected in 43% (6/14) of chronic hepatitis cases and 28% (8/29) of HCCs, whereas cholangitis (n = 6), biliary carcinoma (n = 18) and normal liver (n = 15) all tested negative for DCH. Furthermore, in DCH-associated cases, the histologic features of inflammation and neoplasia, and the viral distribution on ISH were strikingly similar to those seen with HBV-associated disease. Several histological features common in human HBV-associated hepatitis, including piecemeal necrosis and apoptotic bodies, were identified in DCH-positive cases of chronic hepatitis. In two cases of HCC examined, the proliferation index in regions that were ISH-positive was higher than in ISH-negative regions. The intracellular distribution of virus in both hepatitis and HCC demonstrated that viral nucleic acid is present in both nuclear and cytoplasmic forms. Collectively, these findings demonstrate a compelling association between DCH and some cases of chronic hepatitis and hepatocellular carcinoma in the cat that mirrors features of HBV-associated hepatopathies. Future investigations of viral epidemiology and natural history are needed to establish the impact of DCH on feline health.

1997 ◽  
Vol 31 (3) ◽  
pp. 330-337 ◽  
Author(s):  
Michael H Woo ◽  
Thomas G Burnakis

Objective To review the indications, efficacy, and toxicity of interferon alfa in the treatment of chronic hepatitis B and C. Data Sources English-language literature pertaining to chronic hepatitis B and C and their management with interferon reported between 1980 and June 1995 was identified through computer searches using MEDLINE and through extensive searching of bibliographies and identified articles. Data Synthesis Two major causes of chronic hepatitis are hepatitis B virus and hepatitis C virus (HBV and HCV). Worldwide, HBV infection is a major cause of cirrhosis and hepatocellular carcinoma, but in the US it is mainly a disease of high-risk groups. In the US, and particularly the southern portion, HCV is more common. Like HBV, HCV also may cause cirrhosis and hepatocellular carcinoma. Except for interferon therapy, the ability to effectively treat chronic hepatitis is limited. Interferon has antiviral, antiproliferative, and immunomodulatory activity. This agent is indicated in patients who have histologic evidence of chronic hepatitis and ongoing viral replication. Thirty percent to 40% of patients with HBV achieve loss of serum HBV e antigen and HBV DNA after treatment with interferon alfa 5 million units/d or 10 million units three times weekly for 16 weeks. Fifty percent of patients with chronic HCV respond to interferon 3 million units three times weekly for 6 months, but half of these relapse within the next 6 months. Prolonged use (18 months) may provide longer term responses in HCV. Adverse effects are common, often dose-dependent, and usually transient. A flu-like syndrome occurs early in the treatment, but fatigue is the most common adverse effect and persists throughout therapy. Long-term interferon treatment has not been extensively evaluated and the impact on survival rates is not known. Conclusions Interferon is the only agent to have shown a consistent therapeutic effect on chronic hepatitis. Response of HBV to interferon is usually sustained, while a recurrence of HCV occurs in 50% of those who initially respond. Despite the benefits of interferon, its adverse effects and impact on hepatitis must be considered before treatment can be freely advocated.


2021 ◽  
Vol 9 (5) ◽  
pp. 968
Author(s):  
Jan-Hendrik Bockmann ◽  
Matin Kohsar ◽  
John M. Murray ◽  
Vanessa Hamed ◽  
Maura Dandri ◽  
...  

Background: The prevalence of metabolic and cardiovascular diseases is rising worldwide. However, little is known about the impact of such disorders on hepatic disease progression in chronic hepatitis B (CHB) during the era of potent nucleo(s)tide analogues (NAs). Methods: We retrospectively analyzed a single-center cohort of 602 CHB patients, comparing the frequency of liver cirrhosis at baseline and incidences of liver-related events during follow-up (hepatocellular carcinoma, liver transplantation and liver-related death) between CHB patients with a history of diabetes, obesity, hypertension or coronary heart disease (CHD). Results: Rates of cirrhosis at baseline and liver-related events during follow-up (median follow-up time: 2.51 years; NA-treated: 37%) were substantially higher in CHB patients with diabetes (11/23; 3/23), obesity (6/13; 2/13), CHD (7/11; 2/11) or hypertension (15/43; 4/43) compared to CHB patients without the indicated comorbidities (26/509; 6/509). Multivariate analysis identified diabetes as the most significant predictor for cirrhosis (p = 0.0105), while comorbidities did not correlate with liver-related events in pre-existing cirrhosis. Conclusion: The combination of metabolic diseases and CHB is associated with substantially increased rates of liver cirrhosis and secondary liver-related events compared to CHB alone, indicating that hepatitis B patients with metabolic comorbidities warrant particular attention in disease surveillance and evaluation of treatment indication.


Author(s):  
Jie Li ◽  
Hwai-I Yang ◽  
Ming-Lun Yeh ◽  
Michael H Le ◽  
An K Le ◽  
...  

Abstract Background Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and HBsAg seroclearance incidence in CHB patients. Methods In a retrospective cohort study of 6,786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups. Results Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in antiviral treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (HR: 0.19, 95% CI: 0.12-0.33, P<0.001, 0.21, 95% CI: 0.09-0.51, P=0.001, respectively) in antiviral treated patients, but not in untreated patients. Conclusions FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanyuan Ren ◽  
Lei Yang ◽  
Man Li ◽  
Jian Wang ◽  
Huimin Yan ◽  
...  

AbstractHBV infection is recognized as a serious global health problem, and hepatitis B virus infection is a complicated chronic disease leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). New biochemical serum markers could be used to advance the diagnosis and prognosis of HBV-associated liver diseases during the progression of chronic hepatitis B into cirrhosis and HCC. We determined whether the 4210 Da and 1866 Da polypeptides are serum metabolite biomarkers of hepatopathy with hepatitis B virus. A total of 570 subjects were divided into five groups: healthy controls, those with natural clearance, and patients with CHB, LC, and HCC. The 1866 Da and 4210 Da polypeptides were measured by Clin-ToF II MALDI-TOF–MS. There were significant differences in 4210 Da and 1866 Da levels among the five groups (P < 0.001). For the differential diagnosis of CHB from normal liver, the areas under the receiver operating characteristic (ROC) curve of 4210 Da and 1866 Da and their combination via logistic regression were 0.961, 0.849 and 0.967. For the differential diagnosis of LC from CHB, the areas under the ROC curve were 0.695, 0.841 and 0.826. For the differential diagnosis of HCC from CHB, the areas under the ROC curve were 0.744, 0.710 and 0.761, respectively. For the differential diagnosis of HCC from LC, the areas under the ROC curve of 4210 Da and 1866 Da were 0.580 and 0.654. The positive rate of 1866 Da was 45.5% and 69.0% in AFP-negative HCC patients and that of 4210 Da was 60.6% 58.6% in AFP-negative HCC patients of the study HCC vs. CHB and HCC vs. LC. The 4210 Da and 1866 Da polypeptide levels were positively correlated with HBV DNA levels (P < 0.001, r = 0.269; P < 0.001, r = 0.285). The 4210 Da and 1866 Da polypeptides had good diagnostic value for the occurrence and progression of HBV-related chronic hepatitis, liver cirrhosis and hepatocellular carcinoma and could serve to accurately guide treatment management and predict clinical outcomes.


2019 ◽  
Vol 20 (10) ◽  
pp. 785-798 ◽  
Author(s):  
Yigan Zhang ◽  
Huaze Xi ◽  
Xin Nie ◽  
Peng Zhang ◽  
Ning Lan ◽  
...  

Objective: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. Methods: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients’ clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. Results: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients’ Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. Conclusion: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.


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