Significance of liver histology in HBsAg‐positive,IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis

Delladetsima I, Papatheodoridis G V, Tiniakos D G, Hatzakis A & Tassopoulos N C
(2012) Histopathology  61, 881–888 Significance of liver histology in HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis Aims: The natural course of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus (HBV)‐related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients. Methods and results: Fifty patients with HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty‐six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre‐existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P = 0.034). Conclusions: Histological information is very important for the prognosis of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.     

Hepatitis B virus genotype B with G1896A and A1762T/G1764A mutations is associated with hepatitis B related acute-on-chronic liver failure

The existence of statistical associations between hepatitis B‐related acute‐on‐chronic liver failure and both hepatitis B virus (HBV) genotype and mutations in the basal core promoter (BCP) and precore (PC) regions needs to be confirmed. A total of 322 patients with a chronic HBV infection, including 77 with hepatitis B‐related acute‐on‐chronic liver failure, 109 with hepatocellular carcinoma (HCC) and 136 with chronic hepatitis B (CHB) were enrolled. The HBV genotype and the presence of mutations in the BCP/PC regions were determined by direct sequencing, and the frequencies were compared in the three patient groups. Overall, 198/322 (61.5%) were infected with genotype B and 124/322 (38.5%) with genotype C. Genotype B was significantly more frequent in patients with acute‐on‐chronic liver failure than CHB (92.2% vs. 60.3%, P < 0.001). As a contrast, genotype C was more common in patients with HCC than CHB (58.7% vs. 39.7%, P = 0.003). In genotype B patients, the A1762T/G1764A, A1846T, and G1896A mutations were significantly more prevalent in patients with acute‐on‐chronic liver failure than CHB (50.7% vs. 28.0%, P = 0.004; 59.2% vs. 34.1%, P = 0.002; 69.0% vs. 41.5%, P = 0.001, respectively). In multivariate analysis, the risk factors for acute‐on‐chronic liver failure were genotype B, A1762T/G1764A, and G1896A. In conclusion, CHB patients with genotype B, G1896A, and A1762T/G1764A had a higher tendency to develop liver failure than patients with genotype C. Therefore, HBV genotyping and detecting G1896A and A1762T/G1764A mutations might have important clinical implications as predictive risk factors for hepatitis B‐related acute‐on‐chronic liver failure. J. Med. Virol. 83:1544–1550, 2011. © 2011 Wiley‐Liss, Inc.     

Long‐term follow‐up of patients with hepatitis C with a normal alanine aminotransferase

An attempt was made to identify factors influencing the cumulative probability of an increased alanine aminotransferase (ALT) level and hepatocarcinogenesis in hepatitis C patients with a normal ALT level initially. A total of 398 consecutive patients with a normal ALT level initially for 6 months or more and follow‐up period longer than 3 years during the period January 1995 to December 2004 were included. Patients were classified by ALT level into three groups: Group A (3–20 IU/L), Group B (21–30 IU/L), and Group C (31–35 IU/L). Factors associated with the cumulative probability of increased ALT level and hepotocarcinogenesis were evaluated. Women in groups B and C and men in Group C showed high cumulative probabilities of increased ALT levels. Factors associated with increased ALT were a high ALT level (Group B, relative risk; 1.758 [95% confidence interval: 1.290–2.392], P < 0.001, Group C, 3.328 [2.256–4.909], P < 0.001), high lactate dehydrogenase level (2.352 [1.445–3.829], P = 0.001), or low total cholesterol level (1.957 [1.330–2.882], P = 0.001). Factors associated with incidence of hepatocellular carcinoma were increased age (3.088 [1.025–9.308], P = 0.045), high ALT level (Group C, 5.803 [1.530–22.066], P = 0.010), and high total bilirubin level (8.309 [2.235–30.888], P = 0.002). In patients with hepatitis C with a normal ALT level initially, an ALT level of 21–35 IU/L is a risk factor for an increased ALT level and hepatocarcinogenesis. J. Med. Virol. 81:446–451, 2009. © 2009 Wiley‐Liss, Inc.     

Epidemiology of hepatitis B and hepatitis C virus infections among hemodialysis patients in Khartoum, Sudan

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important for health planners and service providers. A cross‐sectional study was conducted to investigate the seroprevalence and associated risk factors for markers of HBV (HBsAg) and anti‐HCV among hemodialysis patients at the Ahmed Gasim hemodialysis unit, Sudan. Structured questionnaires were used to obtain socio‐demographic data and sera were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti‐HCV). Of the 353 patients enrolled in the study, HBsAg and anti‐HCV were detected in 16 (4.5%) and 30 (8.5%) patients, respectively. None of the patients were co‐infected with HBV and HCV. Multivariate analysis showed that duration of dialysis was significantly associated with anti‐HCV seropositivity [OR = 1.1, 95% CI = 1.2–1.3; P = 0.024]. No other socio‐demographic or clinical characteristics (age, sex, level of education, history of surgery, and number of units of blood transfused) were significantly associated with HBsAg or anti‐HCV seropositivity. The results of this study suggest that HBsAg and anti‐HCV have low prevalence among hemodialysis patients in Khartoum. Longer duration of dialysis was a risk factor for anti‐HCV. J. Med. Virol. 84:52–55, 2011. © 2011 Wiley Periodicals, Inc.     

The association of hepatitis C virus infection with the prognosis of chronic hemodialysis patients: A retrospective study of 3,064 patients between 1999 and 2010

The prevalence of hepatitis C virus (HCV) infection is high among patients receiving chronic hemodialysis. To clarify the risk ratio of HCV infection with respect to mortality and prognosis in chronic hemodialysis patients, a retrospective longitudinal cohort study was conducted in 2010 and involved 3,064 patients receiving chronic hemodialysis at nine dialysis facilities in Hiroshima, Japan, who were recruited from 1999 to 2003. Logistic regression and Cox hazards models were used to estimate the mortality risk among hemodialysis patients. Among the patients, 422 (14.0%) were positive for HCV RNA. HCV RNA positivity was associated with death in the logistic model (adjusted odds ratio = 1.79; P < 0.001). However, it was not a risk factor for the reduced of survival rate in the Cox proportional hazard model (adjusted risk ratio = 1.07; P = 0.4138). In summary, among hemodialysis patients, HCV RNA is correlated with the mortality rate; however, it is not significantly correlated with prognosis in terms of survival time. On the other hand, diabetes and age at dialysis onset are significantly correlated with survival. Diabetes control treatment should be preferentially selected for hemodialysis patients, and antiviral therapy for HCV should be introduced based on the clinical state of the patient. J. Med. Virol. 87:1558–1564, 2015. © 2015 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc.     

Elevated post‐transfusion serum transaminase values associated with a highly significant trend for increasing prevalence of anti‐Vesivirus antibody in Korean patients

A highly significant increase in anti‐Vesivirus (family Caliciviridae) antibody prevalence, along the axis from healthy blood donors; donors with elevated transaminase; patients with clinical hepatitis; and patients with post‐transfusion/dialysis hepatitis, has been reported in human sera from the USA and Europe. Asian samples have now been tested retrospectively using serology and enzyme immunoassay (EIA) with a Vesivirus partial‐capsid antigen expressed as a fusion protein. Anti‐vesiviral antibodies were measured by optical densities (OD₆₅₀) and compared in patients separated by age, gender and Groups A–F as follows: Control Group A, an Experimental Group B, which was divided further into Group C, patients with elevated enzymes (alanine transaminase (ALT), aspartate transaminase (AST), and γ‐glutamyl transpeptidase (γ‐GT); Group D, patients receiving transfused blood; Group E, patients with high enzyme levels after transfusion; and Group F, hepatitis B and C positive patients. Using multivariate logistic regression analyses, a significantly greater proportion of patients receiving transfusion(s), were positive for anti‐Vesivirus antibody compared with non‐transfused patients (P = 0.008; OR: 3.86, 95% CI: 1.43–10.43). Also, anti‐Vesivirus antibody was significantly associated with elevated biochemical liver function tests: ALT ≥120 IU or AST ≥ 120 IU (P = 0.017; OR: 4.23, 95% CI: 1.30–13.80). In the blood transfusion group, anti‐Vesivirus antibody was significantly correlated with high enzyme levels (ALT, P = 0.018; AST, P = 0.010; γ‐GT, P = 0.020). These data provide serologic evidence of vesiviral transfusion–transmission‐associated disease, which could include infection of any organ system where cytopathology resulted in high levels of either ALT or AST. J. Med. Virol. 84:1943–1952, 2012. © 2012 Wiley Periodicals, Inc.     

Low prevalence of anti-hepatitis C virus antibodies in female hemodialysis patients without blood transfusion: A multicenter analysis

To investigate whether nosocomial infection with hepatitis C virus (HCV) in chronic hemodialysis patients is related primarily to hemodialysis procedures, a multicenter analysis was carried out on 2,132 chronic hemodialysis patients (male: 1,274, female: 858) from 23 dialysis units using a second-generation anti-HCV antibody assay. The prevalence of anti-HCV antibodies in patients with blood transfusion (29.9%) was significantly higher (P < .0001) than in those without blood transfusion (7.6%). Although the prevalence of anti-HCV antibodies increased with the length of hemodialysis in males without blood transfusion, it did not increase even after long-term hemodialysis (more than 5 years) in females without blood transfusion, who exhibited a rate (1.9%) similar to that of healthy blood donors in Japan. There was a significant correlation between the presence of anti-HCV antibodies and anti-HBs antibody in males without blood transfusion. In anti-HBs antibody-negative male patients without blood transfusion, the prevalence of anti-HCV antibodies was significantly lower compared with anti-HBs antibody-positive male patients without blood transfusion. There was marked difference in the prevalence rate in patients without blood transfusion among dialysis units, and there was no correlation between the prevalence and the mean period of dialysis of each dialysis unit. Although nosocomial infection with HCV appears to be related to the hemodialysis environment, the low prevalence of anti-HCV antibodies in females suggests that dialysis procedures per se may not present the risk of hepatitis C virus infection. © 1996 Wiley-Liss, Inc.     

Lack of a strong association between HLA class II,tumour necrosis factor and transporter associated with antigen processing gene polymorphisms and virological response to α‐interferon treatment in patients with chronic hepatitis C

The aim of the study was to investigate whether polymorphisms of the HLA class II, tumour necrosis factor (TNF) and transporter associated with antigen processing (TAP) genes influence the response to α‐interferon in patients with chronic hepatitis C. Twenty‐seven sustained responders and 55 non‐responders to α‐interferon monotherapy were investigated. HLA‐DRB1, DQA1, DQB1, TNFA, TNFB, TAP1 and TAP2 alleles were determined by PCR‐based molecular techniques. Sustained virological response was defined as undetectable serum hepatitis C virus (HCV) RNA for at least 3 years after the end of treatment. Probability (P) values were corrected for the number of alleles tested (P_c). Viral genotype 1b was more frequent in responders than in non‐responders (56% vs. 26%, P = 0.009). HLA‐DQB1*02 occurred less frequently in responders than in non‐responders (14.8% vs. 29%, P_c not significant). HLA‐DRB1*11 and DQB1*0602 were found in 22.2% and 9.3% of responders and in 10.9% and 1.8% of non‐responders, respectively (P_c not significant). There was no difference in the distribution of TNF alleles in the two groups. Twenty‐four (88.8%) responder patients as compared with 34 (61.8%) non‐responders were TAP1*0101 homozygous (P_c not significant). Thus, in European Caucasoids with chronic hepatitis C, we could not demonstrate a strong association between HLA class II, TNF, and TAP gene polymorphisms and response to interferon treatment.     

CD34 and microtubule-associated protein 2 expression in dysembryoplastic neuroepithelial tumours with an emphasis on dual expression in non-specific types

Sung C O, Suh Y‐L & Hong S‐C
(2011) Histopathology 59 , 308–317 CD34 and microtubule‐associated protein 2 expression in dysembryoplastic neuroepithelial tumours with an emphasis on dual expression in non‐specific types Aims: Three histological variants of dysembryoplastic neuroepithelial tumour (DNT) have been described, namely, simple, complex and non‐specific. However, the concept of non‐specific variants of DNT remains controversial, because they cannot be accurately distinguished by histological findings alone from ordinary gliomas. The aim was to characterize further the non‐specific histological forms of DNT. Methods and results: Forty‐one DNTs classified as three histological forms were investigated with CD34 and microtubule‐associated protein 2 (MAP2) immunohistochemistry. CD34 immunoreactivity was more frequently observed in non‐specific DNT types (16/18 cases; 88.9%) than in classic types (6/23 cases; 26.1%) (P < 0.001). Peritumoral CD34 expression of non‐neoplastic cells was significantly associated with CD34‐positive tumours (20/22 cases; 90.9%) than with CD34‐negative tumours (3/19 cases; 15.8%) (P < 0.001). MAP2 positivity in oligodendroglia‐like cells or glial elements was significantly different between classic types and non‐specific types (P = 0.025). CD34 and MAP2 immunoreactivities were significantly more frequent in non‐specific types (83.3%) than in simple (10%) and complex forms (30.8%) (P < 0.001). Conclusions: Non‐specific DNTs are glioneuronal tumours that have a heterogeneous population of cells with more immature neuronal and glial phenotypes. Furthermore, with regard to practical implications, combined analysis of CD34 and MAP2 is useful in distinguishing DNTs from particularly diagnostically challenging mimics.     

Antibodies to hepatitis C virus in uremic patients on continuous ambulatory peritoneal dialysis.

The prevalence of antibody to hepatitis C virus (anti-HCV) among 101 uremic patients receiving continuous ambulatory peritoneal dialysis (CAPD) was evaluated using a synthetic peptide-based HCV antibodies enzyme immunoassay. Thirty (29.7%) were found anti-HCV positive. This is significantly higher than 500 unselected paid blood donors (4.2%, P less than 0.0001). Among CAPD patients, anti-HCV positivity was found more frequently in patients who had received frequent and longer duration of hemodialysis previously (40.4% vs. 20.4%, P less than 0.05). These findings suggest that hemodialysis patients have a higher risk of HCV infection. At present, CAPD may be a suitable way to reduce the incidence of HCV infection in uremic patients.     

Advanced histology and impaired liver regeneration are associated with disease severity in acute-onset autoimmune hepatitis

Fujiwara K, Nakano M, Yasui S, Okitsu K, Yonemitsu Y & Yokosuka O
(2011) Histopathology 58 , 693–704
Advanced histology and impaired liver regeneration are associated with disease severity in acute‐onset autoimmune hepatitis Aims: Some cases of acute‐onset autoimmune hepatitis (AIH) develop into severe or fulminant forms showing massive/submassive hepatic necrosis, and have a poor prognosis. The pathological features of acute‐onset AIH remain uncertain. Ductular (intermediate) hepatocytes after massive/submassive necrosis may serve as hepatic progenitor cells, and could be seen as cytokeratin 7 (CK7)‐positive hepatocytes in immunohistochemistry. Therefore, the aim was to examine histological features to obtain a better evaluation of acute‐onset AIH. Methods: The histological features of 27 clinically acute‐onset AIH patients were examined by immunohistochemistry using CK7. Results: On staining for CK7, intermediate hepatocytes were less commonly present (P < 0.001) and ductular reactions were more commonly present (P < 0.001) in severe/fulminant patients than in non‐severe ones. In severe and fulminant patients, intermediate hepatocytes and intralobular progenitor cells were more commonly present (P < 0.005 and P < 0.05, respectively) and ductular reactions were less commonly present (P = 0.007) in recovered patients than in dead ones. Severe patients had more clinically and histologically advanced disease. Conclusions: Immunohistochemical evalution using CK7 might be a useful tool for evaluating liver regeneration, and intermediate hepatocytes and progenitor cells might play an important role in liver regeneration after massive and submassive necrosis in acute‐onset AIH.     

Incidence of hepatocellular carcinoma in patients with chronic hepatitis B virus infection who have normal alanine aminotransferase values

The importance of alanine aminotransferase (ALT) levels in the progression of hepatitis B virus (HBV) infection remains a subject of debate. This study sought to identify independent risk factors involved in development of hepatocellular carcinoma (HCC), particularly in patients with chronic HBV infection who have normal ALT values. Data from 381 consecutive hepatitis B patients were analyzed with average ALT integration values ≤40 IU/L and follow‐up periods of >3 years. Integration values were calculated from biochemical tests, and serological markers associated with the cumulative incidence of HCC were analyzed. HCC developed in 17 of the 381 patients (4.5%) during the follow‐up period. Male sex (hazard ratio, 6.011 [95% confidence interval: 1.353–26.710], P = 0.018), high HBV‐DNA levels (≥5.0 log copies/ml; 5.125 [1.880–13.973], P = 0.001), low platelet counts (<15.0 × 10⁴/mm³; 4.803 [1.690–13.647], P = 0.003), and low total cholesterol levels (<130 mg/dl; 5.983 [1.558–22.979], P = 0.009) were significantly associated with greater incidence of HCC development. High HBV‐DNA levels and low platelet counts are associated with the development of HCC in patients infected with hepatitis B who have normal ALT values. Therefore, maintenance of low HBV‐DNA levels is important for the prevention of HCC in patients with low platelet counts, particularly in patients whose ALT values fall within the current normal range. J. Med. Virol. 82:539–545, 2010. © 2010 Wiley‐Liss, Inc.     

Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study

Matsukuma S, Takeo H, Kono T, Nagata Y & Sato K
(2012) Histopathology  61, 857–862 Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study Aims: This study has attempted to elucidate the clinicopathological features of aberrant cytokeratin 7 (CK7) expression by centrilobular hepatocytes. Methods and results: A total of 113 liver biopsy specimens from patients with common non‐neoplastic liver diseases, including hepatitis B or C, non‐alcoholic steatohepatitis, alcoholic liver disease and other diseases were examined. In 56 specimens (49.6%), CK7‐positive centrilobular hepatocytes (CK7 + CHs) were identified and sometimes showed binuclear features. CK7 + CHs were associated with patients’ older age (P = 0.004), higher serum levels of aspartate aminotransferase (P = 0.016) and γ‐glutamyltransferase (P = 0.006), centrilobular fibrosis (P < 0.001), prominent thickening of hepatocytic plates (P < 0.001) and higher scores of total and periportal CK7‐positive hepatocytes (both P < 0.001), but were not correlated with gender, steatosis, serum levels of total bilirubin or alanine aminotransferase. In 55 cases of hepatitis B and hepatitis C only, CK7 + CHs were related to a higher stage of fibrosis (P = 0.006). Conclusion: CK7 + CHs occur relatively frequently in non‐neoplastic liver disease, associated with centrilobular scarring and the presence of CK7‐positive periportal hepatocytes, and appear to be a non‐specific phenomenon with respect aetiology of underlying disease. CK7 + CHs may represent age‐dependent activation of hepatic progenitor cells or a regenerative phenomenon of hepatocytes themselves, both of which might contribute to liver regeneration.     

Do steatosis and steatohepatitis impact on sustained virological response (SVR) rates in patients receiving pegylated interferon and ribavirin for chronic hepatitis C infection?

The impact of steatosis on treatment response in chronic hepatitis C infection is controversial. The aim of this study was to determine whether steatosis ± steatohepatitis on pre‐treatment liver biopsy influenced sustained virological response (HCV RNA negative 6 months after completing therapy) in patients with chronic hepatitis C infection treated with pegylated interferon‐α and ribavirin. One hundred and seventy‐nine patients, median age 46 years (interquartile range 40–52), treated between 2001 and 2005. Histological evidence of steatosis was present in 93 patients (52%) and steatohepatitis in 33 patients (18%), 31 patients (17.3%) were cirrhotic. There were 106 (59%) responders, who were similar to non‐responders in respect to gender, age, and pre‐treatment ALT. On univariate analysis, infection with genotype 2 or 3 was associated with sustained virological response (odds ratio 6.5 (95% CI, 3.3–12.5); P < 0.0001), whereas cirrhosis and patient weight were associated with a reduced response (odds ratios 0.23 (95% CI, 0.11–0.48); P < 0.0001, and 0.97 (95% CI, 0.95–0.99); P < 0.01, respectively); steatohepatitis but not steatosis impacted on the likelihood of achieving sustained virological response (odds ratio 0.37 (95% CI, 0.17–0.77); P = 0.009, and P = 0.18, respectively). Multivariate analysis revealed that infection with genotype 1 or 4 (odds ratio 0.09 (95% CI, 0.03–0.32); P < 0.001) and pre‐treatment weight (odds ratio 0.94 (95% CI, 0.90–0.98); P = 0.002) were the only variables associated independently with sustained virological response. In chronic hepatitis C infection, although steatosis was associated with steatohepatitis, neither was shown to affect sustained virological response, which was influenced by genotype, patient weight and the presence of cirrhosis. J. Med. Virol. 82:958–964, 2010. © 2010 Wiley‐Liss, Inc.     

Hepatitis A viral load in relation to severity of the infection

A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty‐four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self‐limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real‐time RT‐PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P < 0.001). Viremia persisted for 14.2 ± 5.8 days in patients with severe infection and 21.4 ± 10.6 days in those with acute hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real‐time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV‐infected hepatocytes, and in turn severe disease might be induced. J. Med. Virol. 83:201–207, 2011. © 2010 Wiley‐Liss, Inc.     

Early Increased Ficolin‐2 Concentrations are Associated with Severity of Liver Inflammation and Efficacy of anti‐Viral Therapy in Chronic Hepatitis C Patients

Ficolin‐2 is a kind of human serum complement lectin with a structure similar to mannan‐binding lectin (MBL), and it has been implicated in innate immunity. Recent studies have shown that complement pathway activation may contribute to hepatitis. However, the relationship between ficolin‐2 and viral hepatitis remains largely elusive. The aim of this study was to determine the dynamics of ficolin‐2 in patients with chronic hepatitis C. Forty nine patients who had not yet received therapy [24 patients with abnormal alanine aminotransferase (ALT) levels (>40 U/L) and 25 patients with normal ALT levels (≤40 U/L)], 28 patients with hepatitis C who received therapy for 2 weeks and 16 patients received therapy for a full month or longer were included in the study. A sandwich enzyme‐linked immunosorbent assay (ELISA) was used to measure the ficolin‐2 concentrations in all serum samples of patients and 42 healthy donors. We found the concentrations of ficolin‐2 were significantly higher in chronic hepatitis C patients with abnormal ALT values than in chronic hepatitis C patients with normal ALT values and healthy controls. Ficolin‐2 concentrations in chronic hepatitis C patients with abnormal ALT values were positively correlated with ALT levels (*P < 0.05). After therapy, the concentrations of ficolin‐2 decreased and accompany with ALT and Hepatitis C virus (HCV) RNA levels. Then, we found ficolin‐2 concentrations in rapid viral response (RVR) group decreased significantly (*P < 0.05), while in non‐RVR group, ficolin‐2 decreased slightly (P > 0.05). Our findings suggest that early increased ficolin‐2 is highly correlated with hepatic inflammation and rapid viral response.     

Specific mutations in the enhancer II/core promoter/precore regions of hepatitis B virus subgenotype C2 in Korean patients with hepatocellular carcinoma

Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to be related to hepatocellular carcinoma (HCC). This cross‐sectional case–control study examined the relationship between HCC and mutations in the enhancer II/core promoter and precore regions of HBV by comparing 135 Korean HCC patients infected with HBV genotype C2 (HBV/C2; HCC group) with 135 age‐, sex‐, and hepatitis B e antigen (HBeAg) status‐matched patients without HCC (non‐ HCC group). Age and sex were also matched between HBeAg‐positive and ‐negative patients. The prevalence of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was evaluated in this population. The prevalence of the T1653 mutation in the box α region, the A1689 mutation in between the box α and β regions, and the T1762/A1764 mutations in the basal core promoter region was significantly higher in the HCC group compared to the non‐HCC group (8.9% vs. 2.2%, P = 0.017; 19.3% vs. 4.4%, P < 0.001; and 60.7% vs. 22.2%; P < 0.001). Among HBeAg‐negative patients, the frequency of the T1653 mutation was higher in the HCC group. Regardless of HBeAg status, the prevalence of the A1689, and T1762/A1764 mutations was higher in the HCC group than in the non‐HCC group. However, no association was observed between mutations in the precore region and HCC. Upon multivariate analysis, the presence of the T1653, A1689, and T1762/A1764 mutations was an independent predictive factor for HCC. The addition of the T1653 or A1689 mutation to T1762/A1764 increased the risk of HCC. In conclusion, the T1653, A1689, and/or T1762/A1764 mutations were associated with the development of HCC in Korean patients infected with HBV/C2. J. Med. Virol. 81:1002–1008, 2009. © 2009 Wiley‐Liss, Inc.     

Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection

Antibody to hepatitis B surface antigen (HBsAg) (anti‐HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti‐HBs (concurrent HBsAg/ anti‐HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti‐HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti‐HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti‐HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365–49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226–4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788–7.421; P < 0.001) and concurrent HBsAg/anti‐HBs (OR, 4.336; 95% CI, 1.956–9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti‐HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti‐HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C. J. Med. Virol. 81:1531–1538, 2009. © 2009 Wiley‐Liss, Inc.     

Eighteen-year follow-up cohort study on hepatitis B and C virus infections related long-term prognosis among hemodialysis patients in Hiroshima

This study aimed to investigate the prevalence trend of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and their genotype distribution among hemodialysis patients, determining their long-term prognosis and the risk factors to the mortality. This cohort study used both the medical data and the blood samples of hemodialysis patients at nine dialysis centers in Hiroshima from 1999 to 2017. Hepatitis B surface antigen (HBsAg) and anti-HCV were screened and then amplification was done to positive sera by polymerase chain reaction for genotyping. Data were employed for multiple regressions to determine the associated risk factors. A total of 3968 patients were subdivided into three groups: who started hemodialysis before 1990, during 1991 to 2001, and after 2002. The periodic prevalence of HBsAg decreased from 2.8% to 1.3% and that of anti-HCV from 33.3% to 9.5% in the three groups. By multiple regressions, the adjusted hazard ratio of diabetes mellitus (DM) ranges from 1.59 to 2.12 and that of HCV RNA positivity ranges from 1.18 to 1.48 (P < .05). Heart failure is the primary cause of death in all groups. Genotype C2 is predominant for HBV and genotype 1b is predominant for HCV. The decreasing trend of both HBV and HCV was found in the cohort. DM and HCV RNA were the significant risk factors leading to poor prognosis among hemodialysis patients. The similar genotype distribution of both HBV and HCV was found as general population. This alarmed to provide early diagnosis, prompt, and adequate treatment to HCV infection among hemodialysis patients.