A case of non-islet cell tumour hypoglycaemia due to advanced hepatocellular carcinoma secondary to previously undiagnosed chronic HBV-infection

Case summary An 11-year-old male neutered domestic shorthair cat presented with behavioural changes. Physical examination revealed bradycardia and a cranial abdominal mass. The cat was persistently hypoglycaemic (1.2 mmol/l; reference interval [RI] 3.5–5.5 mmol/l) with decreased fructosamine concentration suggesting chronic hypoglycaemia, and decreased insulin concentration excluding insulinoma. Alanine aminotransferase activity was markedly increased (1219.31 U/l; RI 15–60 U/l). On staging CT a large, multilobulated hepatic mass was identified, with no evidence of metastatic disease. After surgical removal serum glucose concentration and heart rate quickly returned to within the RIs. Histopathology was consistent with a solid-to-trabecular, well-differentiated, hepatocellular carcinoma. There was no recurrence of signs or mass during 8 months of follow-up, and the cat was still alive 20 months after surgery. Relevance and novel information Non-islet-cell tumour hypoglycaemia (NICTH) is a rare but life-threatening paraneoplastic syndrome. In humans, hepatocellular carcinoma is the most common epithelial tumour causing NICTH, but these are uncommon in cats, and associated paraneoplastic hypoglycaemia has not been reported. Possible mechanisms include aberrant secretion of big insulin growth factor 2; however, this could not be confirmed. NICTH should be considered in the differential diagnosis of cats with persistent hypoglycaemia.

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Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20190783 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 4

Author(s):

Han Shi ◽

Hongyan He ◽

Suvash Chandra Ojha ◽

Changfeng Sun ◽

Juan Fu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Meta Analysis ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

Abstract Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.

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Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection

Scientific Reports ◽

10.1038/s41598-020-77332-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Huan Deng ◽

Xiude Fan ◽

Xiaoyun Wang ◽

Lu Zeng ◽

Kun Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Early Stage ◽

Hbv Infection ◽

Healthy Controls ◽

Pentraxin 3 ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

AbstractBiomarkers for early diagnosis of hepatocellular carcinoma (HCC) are needed in chronic hepatitis B virus (HBV) infection, a leading cause of HCC. We evaluated whether measurement of serum pentraxin 3 (PTX3) could improve diagnosis of HCC in chronic HBV infection. Data from patients with HBV-related chronic hepatitis (n = 159), cirrhosis (n = 99) and HCC (n = 107), and healthy controls (n = 151) were analyzed. Serum PTX3 concentration was measured by immunoassay. Area under the receiver operating characteristic curve (AUC) was applied to assess diagnostic accuracy. PTX3 levels were significantly higher in HBV patients than in healthy controls (P < 0.001) and in HCC than in chronic hepatitis (P < 0.001) or cirrhosis patients (P < 0.001). PTX3 was an independent risk factor of HCC [odds ratio (OR) 1.617, P < 0.001] and could distinguish HCC in chronic HBV infection [cutoff 9.231 ng/mL, AUC 0.929 with 95% confidence interval (CI) of 0.898–0.953], including α-fetoprotein (AFP) negative [cutoff 8.985 ng/mL, AUC (95%CI) 0.947 (0.908–0.973)] and early-stage HCC [cutoff 9.359 ng/mL, AUC (95%CI) 0.920 (0.885–0.947)]. Combination of PTX3 with AFP improved the discrimination of early HCC from chronic HBV infection [AUC (95%CI) 0.948 (0.918–0.970)]. In short, PTX3 measurement could identify HCC, including AFP-negative and early-stage HCC, in chronic HBV infection.

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Studies on Mutual Relationship between Anti-HBx and sFas, IL-10 or IL-12 in Sera of Cases with Chronic Hepatitis B Infection

Infection International ◽

10.1515/ii-2017-0075 ◽

2014 ◽

Vol 3 (2) ◽

pp. 49-53

Author(s):

Ai-kun Ding ◽

Li-wei Guo ◽

Yong-kong Wang ◽

Wei Liu ◽

Cheng Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Sandwich Elisa ◽

Hbv Infection ◽

Mutual Relationship ◽

Chronic Hbv Infection ◽

Chronic Hbv

Abstract Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas (sFas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role in the development of chronic HBV infection. Methods Total of 90 cases with chronic HBV infection were randomly selected, including 10 of asymptomatic carriers (ASC), 28 of chronic hepatitis B (CHB), 26 of liver cirrhosis (LC) and 26 patients of hepatocellular carcinoma (HCC). Their clinical data and blood samples were collected, and serum was prepared and stored at -73℃. Anti-HBx was detected with an indirect ELISA established in our earlier research, and levels of IL-10, IL-12 and Fas were determined with commercial double-antibody sandwich ELISA kits. The mutual relationship between anti-HBx and IL-10, IL-12 or sFas in serum were analyzed with the software SPSS 20.0. Results All levels of IL-10, IL-12 and sFas in peripheral blood showed a rising trend with development of chronic HBV infection. The levels of IL-10 in ASC, CHB, LC and HCC groups were 13.93 ± 14.40 ng/L, 39.38 ± 20.77 ng/L, 69.06 ± 46.37 ng/L and 62.82 ± 23.42 ng/L, respectively, levels of IL-12 in the 4 groups were 15.64 ± 23.04 ng/L, 68.50 ± 23.14 ng/L, 76.83 ± 12.82 ng/L and 83.74 ± 24.88 ng/L, respectively, and levels of sFas were 58.17 ± 77.42 ng/L, 179.88 ± 104.36 ng/L, 249.22 ± 107.80 ng/L and 252.98 ± 87.65 ng/L, respectively. Twenty-seven out of 90 patients showed a positive result for anti-HBx detection, including 1 in ASC, 4 in CHB, 12 in LC and 10 in HCC group. The levels of IL-10, IL-12 and sFas were higher in anti-HBx positive group than in negative group. Statistical analysis demonstrated significant differences of IL-10 and IL-12 between the two groups (P < 0.05), but the differences of sFas had no statistical significance (P = 0.094). Conclusions Anti-HBx antibody is not protective, and is closely related to IL-10, IL-12 and sFas. It may be an important serum indicator for aggravation from chronic hepatitis B to liver cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.

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Impact of Hepatitis B Virus (HBV) X Gene Mutations on Hepatocellular Carcinoma Development in Chronic HBV Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00661-12 ◽

2013 ◽

Vol 20 (1) ◽

pp. 127-127 ◽

Cited By ~ 1

Author(s):

Jong-Han Lee ◽

Kwang-Hyub Han ◽

Jae Myun Lee ◽

Jeon Han Park ◽

Hyon-Suk Kim

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Gene Mutations ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv ◽

X Gene

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Hepatocellular carcinoma in children and young patients with chronic HBV infection and the usefulness of alpha‐fetoprotein assessment

Cancer Medicine ◽

10.1002/cam4.917 ◽

2016 ◽

Vol 5 (11) ◽

pp. 3102-3110 ◽

Cited By ~ 6

Author(s):

Hitoshi Tajiri ◽

Tomoko Takano ◽

Hideo Tanaka ◽

Kosuke Ushijima ◽

Ayano Inui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Young Patients ◽

Alpha Fetoprotein ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hbv

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Hepatitis B Virus

10.2310/im.5483 ◽

2021 ◽

Author(s):

Ming V. Lin ◽

April Wall

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Infection ◽

Treatment Options ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

Chronic hepatitis B virus (HBV) infection is a major health burden worldwide, with approximately 257 million people with chronic infection. HBV is a small partially double-stranded DNA virus that replicates within the nucleus of the hepatocyte and commonly leads to chronic infection. Chronic HBV infection can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations such as glomerulonephritis or vasculitis. The latter is due to deposition of circulating immune complex in the different tissues. The natural history of HBV infection can be conceptualized as a spectrum encompassing different phases, including immune tolerance, immune clearance, inactive carrier, and reactivation and resolution. The diagnosis of the different phases of chronic HBV infection relies on various HBV serologies, liver enzyme levels, and histology findings. There are currently eight therapies approved for the treatment of HBV. Tenofovir alafenamide was the most recently approved therapy with a better side effect profile compared with tenofovir disoproxil fumarate. With the recent advances in the basic research in hepatitis B, new treatment options may become available in the near-future. This review contains 9 figures, 11 tables and 80 references Key words: cirrhosis, entecavir, Hepadnaviridae, hepatitis B virus, hepatocellular carcinoma, precore mutation, tenofovir

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Hepatitis B Virus

10.2310/em.5483 ◽

2021 ◽

Author(s):

Ming V. Lin ◽

April Wall

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Infection ◽

Treatment Options ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

Chronic hepatitis B virus (HBV) infection is a major health burden worldwide, with approximately 257 million people with chronic infection. HBV is a small partially double-stranded DNA virus that replicates within the nucleus of the hepatocyte and commonly leads to chronic infection. Chronic HBV infection can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations such as glomerulonephritis or vasculitis. The latter is due to deposition of circulating immune complex in the different tissues. The natural history of HBV infection can be conceptualized as a spectrum encompassing different phases, including immune tolerance, immune clearance, inactive carrier, and reactivation and resolution. The diagnosis of the different phases of chronic HBV infection relies on various HBV serologies, liver enzyme levels, and histology findings. There are currently eight therapies approved for the treatment of HBV. Tenofovir alafenamide was the most recently approved therapy with a better side effect profile compared with tenofovir disoproxil fumarate. With the recent advances in the basic research in hepatitis B, new treatment options may become available in the near-future. This review contains 9 figures, 11 tables and 80 references Key words: cirrhosis, entecavir, Hepadnaviridae, hepatitis B virus, hepatocellular carcinoma, precore mutation, tenofovir

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