Had Hepatitis B Virus Infection Research Articles

Dynamic contrast-enhanced CT and clinical features of sarcomatoid hepatocellular carcinoma

PurposeTo investigate the dynamic contrast-enhanced computed tomography (CECT) features and clinical characteristics of sarcomatoid hepatocellular carcinoma (S-HCC).MethodsWe retrospectively reviewed the CECT data and clinical findings of 13 patients (11 male and 2 female, with an average age of 58.6 ± 11.2 years) with pathologically proven S-HCC, including 9 patients with surgical resection and 4 patients with biopsy examination. All patients underwent CECT scans. Two radiologists reviewed and evaluated general features, CECT features and extratumoral features of each lesions based on a consensus.ResultsAmong the thirteen tumors, a mean size of 66.7 mm was observed, ranging in diameter from 30 to 146 mm. Seven of thirteen patients had hepatitis B virus (HBV) infection and an elevation of alpha-fetoprotein (AFP) level. Most of cases located in the right lobe of liver (84.6%, 11/13). Nine of thirteen tumors showed lobulated or wavy contours and infiltrative morphology, while eight tumors presented with unclear margin. The tumor textures were mainly heterogeneous for ischemia or necrosis, with solid components dominantly in all cases. Eight of thirteen tumors exhibited “slow-in and and slow-out” dynamic enhancement pattern in CECT, with a enhancement peak in the portal venous phase. Portal vein or hepatic thrombus, adjacent organs invasion and lymph node metastasis were observed in two patients, respectively. Four of thirteen lesions occurred intrahepatic metastasis and hepatic surface retraction respectively.ConclusionS-HCC gengerally seen in elderly male with HBV infection and elevated AFP level. The CT manifestations including: large diameter, frequently hepatic right lobe involvement, lobular or wavy contours, ill-defined margins, infiltrative morphology, obvious heterogeneity and dynamic enhancement pattern of “slow-in and and slow-out” , contributed to the diagnosis of S-HCC. These tumors usually occurred hepatic surface retraction and intrahepatic metastasis.

Comparison of invasive and non-invasive methods for assessment of liver fibrosis in patients with chronic hepatitis B and hepatitis C virus infections

Introduction: Different methods are employed to determine the severity of chronic viral hepatitis and liver fibrosis Objectives: This study was conducted to compare invasive and non-invasive tests for assessment of liver fibrosis in the patients with chronic hepatitis B and C. Patients and Methods: In this study, the results of liver biopsy based on the METAVIR scoring system were compared with biomarkers, including fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) for identifying liver fibrosis. Results: Out of 194 patients, 63 and 131 patients had hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, respectively. There was a significant difference between patients with METAVIR stages 0-1 and patients with METAVIR stages 2-3, based on the FIB-4, aspartate aminotransferase (AST) to platelet ratio index (APRI) and the mean prothrombin time (PT), international normalized ratio (INR), platelet (PLT), alanine transaminase (ALT) and AST. A correlation was found between the FIB-4 and APRI indices and the METAVIR score of patients with hepatitis. The FIB-4 index, with a cut-off value <1.1 for detecting liver fibrosis in patients with HBV infection, showed sensitivity of 83.3%, specificity of 64.7%. Further, a positive predictive value (PPV) of 35.7%, and a negative predictive value (NPV) of 94.3% was detected. On the other hand, the APRI index, with a cut-off value <0.73, showed 59% sensitivity, 76.5% specificity, PPV of 33.3% and NPV of 86.7%. The FIB-4 index, with a cut-off value <1.47 for detecting liver fibrosis in patients with HCV infection, showed 73.7% sensitivity, 73.2% specificity, PPV of 31.8%, and NPV of 94.3%. Additionally, the APRI index, with a cut-off value <1.7, showed 42.1% sensitivity, 97.3% specificity, PPV of 72.7% and NPV of 90.8%. Conclusion: According to the results, in patients with chronic hepatitis, the severity of liver fibrosis increased with an increase in the APRI and FIB-4 indices. Therefore, these two indices can replace biopsy under certain circumstances.

Factors that Affect the Surveillance and Late-Stage Detection of a Newly Diagnosed Hepatocellular Carcinoma.

Background:Surveillance of hepatocellular carcinoma (HCC) is beneficial for detecting early-stage HCC. The factors that influence adherence to HCC surveillance and late-stage detection have never been evaluated. We investigated the predictive factors that contribute to patients accessing regular HCC surveillance and their association with the detection of late-stage HCC at the time of diagnosis. Methods:We conducted a prospective observational study at Hatyai Hospital (Songkhla, Thailand) between 2014 and 2016. HCC surveillance includes performing hepatic ultrasonography with/without serum alpha-fetoprotein 6–12 months before the detection of HCC. Logistic regression analyses were conducted separately to examine the relationship between the variables and each endpoint. Results:One hundred ninety-nine HCC patients were enrolled in the study; most patients were of low socioeconomic status, 90.5% had less than a bachelor’s degree, and 69.3% of patients had a monthly income of <10,000 baths (US $312.50). Nearly all (93.5%) patients had cirrhosis, 39.7% had hepatitis B virus (HBV) infection, 24.6% had hepatitis C virus infection, and 24.6% had alcohol-related liver disease. The risk of HCC was recognized in 51.8% of patients, and regular HCC surveillance was achieved in 36.2% of patients. Multivariate logistic regression analysis revealed that a monthly income >10,000 baths (US $312.50) (odds ratio [OR], 4.566; p = 0.013), HBV infection (OR, 0.188; p = 0.001), and recognition of patients at risk of HCC (OR, 130.396; p<0.001) were independent predictive factors for adherence to HCC surveillance. Regular HCC surveillance (OR, 0.215; p = 0.003) and recognition of HBV infection (OR, 0.356; p = 0.040) were independent preventive factors for the detection of late-stage HCC at the time of diagnosis. Conclusion:In Thailand, awareness of patients at risk of developing HCC and the rate of regular HCC surveillance are low. Greater awareness will enable physicians to surveil and detect HCC.

Biopsy‐proven liver cirrhosis in young children: A 10‐year cohort study

Young children with liver cirrhosis have a significantly high risk of mortality. However, there are few studies regarding early childhood-onset cirrhosis. This study aims to explore the causes, clinical findings and prognosis of biopsy-proven cirrhosis in infants, toddlers and preschoolers. We enroled young children with biopsy-proven cirrhosis from January 2010. Till January 2020, the study has been going on for 10years. A total of 139 cirrhotic children were enrolled, including 87 boys and 52 girls. The median age at initially histological diagnosis of cirrhosis was 2years old (range: 1month-6years). Sixty-two patients reported yellowish discoloration of sclera and/or skin as an initial symptom. Ninety-three patients had definite aetiologies while 46 had indeterminate causes. Among the confirmed cases, 31 had hepatitis B virus (HBV) infection, accounting for 33.3%. Subsequently, glycogen storage disease was diagnosed in 16 cases and Wilson disease in 14 cases. In these patients with HBV infection, nine finally achieved hepatitis B surface antigen (HBsAg) loss (29.0%) after effective antiviral therapy during the follow-up. Logistic regression revealed that baseline alanine aminotransferase (odds ratio 1.008, p=0.028) was the independent predictor of HBsAg loss. Furthermore, one patient who underwent second biopsies showed histological reverse. HBV infection is an important cause of paediatric cirrhosis in our study. The pathogenesis of HBV-related cirrhosis in early childhood deserves further studies.

Hepatitis B Virus Infection Among Leprosy Patients: A Case for Polymorphisms Compromising Activation of the Lectin Pathway and Complement Receptors.

Thousands of leprosy patients not only suffer from physical deformities, but also either have or have had hepatitis B virus (HBV) coinfection. Polymorphisms of the complement system modulate susceptibility to leprosy, but genetic susceptibility to past or present HBV infection is unknown. We used sequencing and multiplex sequence-specific PCR to genotype 72 polymorphisms of seven genes (MBL2, FCN1, FCN2, FCN3, MASP1, MASP2, C3) encoding components of the lectin pathway, and two genes encoding complement receptors (CR1, VSIG4) in 190 patients, of which 74 were positive for HBsAg and/or anti-HBc (HBV+, 93.2% with a resolved infection) and 116 lepromatous patients, and 408 HBV-blood donors. In addition, we tested for levels of proteins of the lectin pathway. We found no difference between serum concentrations of mannan-binding lectin (MBL), MBL-associated serine proteins (MASP-1, MASP-2, MASP-3, MAp44), ficolin-3 (FCN-3), soluble complement receptor 1 (sCR1) and MBL mediated C4 activation, measured by ELISA or TRIFMA in up to 167 HBV+ and HBV− patients. Haplotypes lowering protein levels or encoding dysfunctional proteins increased susceptibility to HBV infection: MBL2*LYQC (OR = 3.4, p = 0.02), MASP1*AC_CC (OR = 4.0, p = 0.015) and MASP2*1C2-l (OR = 5.4, p = 0.03). Conversely, FCN1*3C2 haplotype, associated with higher gene expression, was protective (OR = 0.56, P = 0.033). Other haplotypes associated with HBV susceptibility were: MASP2*2B1-i (OR = 19.25, P = 0.003), CR1*3A (OR = 2.65, P = 0.011) and VSIG4*TGGRCG (OR = 12.55, P = 0.014). Some polymorphisms in ficolin genes associated with lower protein levels increased susceptibility to leprosy/HBV infection: FCN*1 (OR = 1.66, P = 0.029), FCN2*GGGCAC (OR = 6.73, P = 0.008), and FCN3*del_del_C (OR = 12.54, P = 0.037), and to lepromatous disease/HBV infection: FCN2*TA (OR = 2.5, P = 0.009), whereas FCN2*MAG was associated with increased FCN-2 expression and resistance against coinfection (OR = 0.29, P = 0.026). These associations were independent of demographic factors and did not increase susceptibility to leprosy per se, except MASP2*1C2-l. Associations for FCN2, FCN3, MASP1, MASP2, and VSIG4 variants were also independent of each other. In conclusion, polymorphisms compromising activation of the lectin pathway of complement increase susceptibility to HBV infection, with ficolin polymorphisms playing a major role in modulating the susceptibility among leprosy patients.

The CT and MRI Features of Primary Intrahepatic Lymphoepithelioma-Like Cholangiocarcinoma.

OBJECTIVE. The purpose of our study was to retrospectively characterize the CT and MRI features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). MATERIALS AND METHODS. Eleven patients (10 women and one man; age range, 30-63 years) with 11 pathologically proven LELCCs were enrolled retrospectively from April 2016 to December 2018. Triphasic enhanced images were obtained of all patients: MR images of five patients, CT images of five patients, and both CT and MR images of one patient. The clinical data and CT and MRI findings were reviewed. RESULTS. All LELCC cases were associated with Epstein-Barr virus (EBV) infection. Eight of the 11 patients had hepatitis B virus (HBV) infection. The tumor diameter ranged from 1.1 to 8.7 cm. All tumors were well defined with a smooth or lobulated margin. A cystic area was noted in two of the 11 tumors. After the administration of contrast material, the tumors showed homogeneous (n = 7) or heterogeneous (n = 4) hypervascular arterial enhancement and gradual washout, delayed central scar or irregular enhancement (n = 9), delayed circular thin or incomplete pseudocapsule enhancement (n = 7), and homogeneous hypointensity in the hepatobiliary phase (n = 2). No cirrhosis, focal dilatation of intrahepatic ducts, or satellite nodules were detected. Lymphadenopathy were detected in four patients, appearing as hypervascular enhancement and no necrosis (even in multiple nodes > 3 cm) or as moderate peripheral enhancement and necrosis. CONCLUSION. A liver mass in a middle-aged woman with EBV and HBV infection that appears on CT and MRI to have a well-defined boundary and a combination of hypervascularity, washout, delayed intratumoral enhancement, or pseudocapsule enhancement may suggest an imaging diagnosis of primary LELCC. More cases are needed to better understand this disease.

Abstract 4964: Associations between hepatitis etiology and immune cell infiltration in or around hepatocellular carcinoma

Abstract Background: Previous studies have demonstrated that the abundance of immune cells may be associated with hepatocellular carcinoma (HCC) prognosis. Because HCC has various hepatitis etiologies, we studied the associations between hepatitis etiology and regional lymphocyte infiltration at and beside the tumor. Methods: We collected tumor samples from patients who received curative surgery for HCC. Immunohistochemical staining was performed on tissue slides, which were then scanned using TissueFAXS v4.2 and analyzed using HistoQuest v4.0 (both from TissueGnostics Inc.). We calculated the amount of total T cells (CD3 positive), CD8 T cells (CD8 positive), and macrophages (CD68 positive) inside the tumor (IT), at the tumor margin (TM), and outside the tumor (OT). For analysis at IT and TM, the whole area were examined. For analysis at OT, only the five areas with the highest cell density at the low power fields were analyzed. For each area, we defined low and high cell density according to the median values. We then explored the associations of these cell distributions and HCC etiologies or prognosis. Results: We included HCC samples from 120 patients. Among them, 76 (63%) had hepatitis B virus (HBV) infection, 28 (23%) had hepatitis C virus infection, 14 patients had neither infections, and 1 patient had both HBV and HCV infection. The amount of total T cells (p &amp;lt; 0.001), CD8 T cells (p &amp;lt; 0.001), and total macrophages (p &amp;lt; 0.001) were all significantly higher at TM than at IT. HCV-positive tumors, compared to HBV-positive tumors had more total T cells inside (p = 0.040) and outside the tumors (p &amp;lt; 0.001), but similar total T cells at the margin. On the contrary, the amount of CD8 T cells and total macrophages were similar between HBV-positive and HCV-positive tumors at IT, TM, and OT. Samples of 112 patients included both IT and TM area. Using CD8 cell counts for classification, 40 (33%) were IThighTMhigh, 16 (13%) were ITlowTMhigh, 42 (35%) were ITlowTMlow, and 14 (12%) were IThighTMlow. Patients with ITlowTMlow tumors tended to have poorer overall survival than other patients (p = 0.085), but patients with IThighTMhigh, ITlowTMhigh, and IThighTMlow tumor had similar prognosis (p = 0.770). Hepatitis virus infected tumors were significantly less likely to be ITlowTMlow than hepatitis virus uninfected tumors (33% vs. 69%, p = 0.010); HBV-infected and HCV-infected tumors had similar percentages of ITlowTMlow tumors (68% vs. 65%, p = 0.837). Conclusions: HCV infection was associated with higher total T cell infiltration inside and outside the tumors. Hepatitis virus uninfected tumors were more likely to have low CD8 cells both inside and at the margin of HCC. Citation Format: Yu-Yun Shao, Min-Shu Hsieh, Yun-Ting Tsai, Ying-Chun Shen, Zhong-Zhe Lin, Ann-Lii Cheng, Chih-Hung Hsu. Associations between hepatitis etiology and immune cell infiltration in or around hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4964.

Diabetes Mellitus and Prediabetes in Patients with Hepatocellular Carcinoma in a Tertiary Philippine Hospital

BackgroundDiabetes mellitus (DM) has been shown to be associated with an increased risk for hepatocellular carcinoma (HCC). DM and obesity are coexisting conditions that can increase the risk and severity of nonalcoholic fatty liver disease (NAFLD), leading to HCC even in the absence of cirrhosis. With the rising incidence of HCC and DM worldwide, it is important to identify the clinical characteristics of individuals with DM among those with HCC in our local setting.ObjectivesTo determine the prevalence of DM among Filipino patients with HCC at our institution, determine their demographic and clinical profile, and compare the characteristics of HCC patients with and without DM.MethodologyThis is a retrospective, analytical, cross-sectional study involving patients with HCC seen at The Medical City’s Center for Liver Disease Management and Transplantation from January 2010 to December 2014. A chart review was conducted and patients were grouped according to the presence or absence of DM. Data on demographics, body mass index (BMI), comorbidities, social and family history, risk factors for liver disease, and laboratory test results were gathered. STATA 12.0 was used for data analysis.ResultsWe included 180 patients with HCC in the analysis. The prevalence of type 2 DM and prediabetes was 52.78%. The median age of patients with DM and prediabetes was 65 years, and 58 years for patients without DM (p=0.002). The average BMI was 27.35 + 4.68 for patients with DM, and 25.04 + 5.11 for those without DM (p=0.002). Among the patients without DM, 50.59% had hepatitis B virus (HBV) infection compared to 24.21% of patients with DM (p=0.000). Twenty one percent of patients with DM had cryptogenic cirrhosis compared to 8.24% of patients without DM (p=0.016). Patients with DM had a higher proportion of hypertension (66.32% vs. 42.35%, p=0.001) and dyslipidemia (48.42% vs. 10.59%, p=0.000).ConclusionThe prevalence of DM and prediabetes among HCC patients is higher in our institution compared to findings from previous studies. HCC patients with DM were older, and had increased BMI, higher proportion of hypertension and dyslipidemia, lower incidence of HBV infection, and higher incidence of cryptogenic cirrhosis.

Hepatocellular Carcinoma and Viral Hepatitis in New York City.

The incidence and mortality rate of hepatocellular carcinoma (HCC) are increasing in the United States. Viral hepatitis infection is a primary risk factor for HCC. This study describes the relationship between viral hepatitis and HCC in New York City (NYC). Viral hepatitis cases reported to the NYC Department of Health from 1999-2012 were matched to HCC cases diagnosed from 2001 to 2012 and reported to the New York State Cancer Registry. HCC cases were stratified by the presence or absence of viral hepatitis. Demographic characteristics, factors associated with specific causes of death, and survival time were analyzed for all HCC cases. From 2001-2012, a total of 8827 NYC residents had HCC diagnosed; 38.4% had hepatitis C virus (HCV) infection, 17.9% had hepatitis B virus (HBV) infection, and 2.2% had both. Patients with HCC were predominantly men (74.8%), with equal proportions of white non-Hispanic (28.6%) and Hispanic (28.9%) patients. Those with HBV infection were primarily Asian/Pacific Islanders (63.2%). The median survival time after HCC diagnosis for persons with HBV infection was 22.3 months, compared with 13.1 months for persons with HCV infection, and 6.9 months for noninfected persons. The 5-year survival rate was 37.5% for those with HBV infection, 20.0% for those with HCV infection, 29.5% among coinfected individuals, and 16.1% for those with neither infection reported. In NYC, most persons with HCC have viral hepatitis; the majority of viral hepatitis infections are due to HCV. Survival for persons with HCC differs widely by viral hepatitis status. This study highlights the importance of viral hepatitis prevention and treatment and HCC screening.

Case Report of Relay Liver Transplantation With Graft Infected With Hepatitis B Virus

Reuse of liver graft for transplantation is extremely uncommon. We report the 1st case of reuse of liver graft from a recipient who had hepatitis B virus (HBV) infection, 11 years after the 1st transplantation. Our relay liver transplantation challenged conventional thinking because of late reuse of graft in the presence of HBV infection. Moreover, both the 1st and the 2nd donors were of advanced age. The key questions were whether the liver graft could be reused safely, especially in the setting of HBV infection, and technical concerns during organ procurement and implantation. The absence of HBV replication was confirmed with negative hepatitis B surface antigen and undetectable serum HBV DNA in the 2nd donor. Based on our experience in managing HBV infection after liver transplantation, we were confident that the adequately suppressed HBV infection in the donor would not jeopardize graft function and that the graft would be able to withstand another ischemia-perfusion injury to continue to function well in our recipient.

Effect of pre- and post-treatment α-fetoprotein levels and tumor size on survival of patients with hepatocellular carcinoma treated by resection, transarterial chemoembolization or radiofrequency ablation: a retrospective study.

BackgroundWe evaluated treatment modalities and survival in patients with hepatocellular carcinoma (HCC), by pre-treatment and 3-month post-treatment serum alpha-fetoprotein (AFP) levels and pre-treatment tumor diameters.MethodsWe retrospectively reviewed 57 patients treated for HCC in our department from January 2002 to December 2012, including their sex, type of hepatitis, Child class, pre-treatment tumor size, pre-treatment levels of albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), red blood cells, hemoglobin, and total bilirubin, pre- and 3-month post-treatment serum AFP, and treatment modality (transarterial chemoembolization, resection or radiofrequency ablation). Survival was analyzed at 1, 3, and 5 years after treatment.ResultsThe 57 patients included 44 men and 13 women, of whom 44 had hepatitis C virus (HCV) infection, 3 had hepatitis B virus (HBV) infection, 3 had both HBV and HCV infection, 1 had both HBV and hepatitis D virus infection, and 3 had alcohol-related liver cirrhosis. Both pre- and post-treatment serum AFP levels significantly correlated with recurrent tumor size (P < 0.05 for both). Pre-treatment tumor size did not correlate with recurrent tumor size. Patients who underwent hepatic resection survived significantly longer than those who underwent transarterial chemoembolization or radiofrequency ablation (P < 0.05).ConclusionsSerum AFP level is useful in diagnosing tumor recurrence and predicting prognosis in HCC patients treated by hepatic resection, transarterial chemoembolization, and radiofrequency ablation. Hepatic resection remains the treatment of choice for HCC in suitable patients.

Effect of Ribavirin Therapy on Salivary Gland Function: An Oral Medicine Prespective

Dear Editor, We read with keen interest the recently published paper entitled Ribavirin impairs salivary gland function during combination treatment with pegylated interferon alfa-2a in hepatitis C by Aghemo et al[1] in your esteemed journal. The study described the effect of ribavirin plus interferon therapy (combination therapy) on salivary gland function. However, we think we must put pen to paper with respect to draw the attention of your respectful readers to possible misinterpretation of the data that has been presented. Even at the beginning of the third millennium, hepatitis C virus (HCV) infection remains a major global public health problem, and to date, combination therapy seems to be the most effective treatment option. Nonetheless, this treatment might result in some side effects such as lichen planus, skin rash, psychological disturbances, poor appetite, anemia, and leucopenia [2]. Derived results of the study by Aghemo et al might be affected by some confounding factors. First, although the authors had mentioned that a limitation of their study was using patients who had hepatitis B virus (HBV) infection as the control subjects, it cannot iron out all the attributed results of choosing an unsuitable control group. Previous studies have shown that HCV infection in the epithelial cells of the salivary glands is a factor associated with the development of sialadenitis and Sjogren's syndrome [3]. However, to our knowledge, no previous study has shown such a conclusive correlation with HBV infection. Because of the observed inconsistencies in the findings of these studies, it does not seem appropriate to conclude that the use of drugs is the sole cause of salivary gland malfunction. In addition, it is unclear that why the authors used such a small control group; the use of a small sample size raises questions regarding the reliability of the rate of side effects expressed by the patients in this group. An advantage of their study was that they used stimulated saliva for evaluating sialadenitis. Previous studies have confirmed that stimulated whole saliva is especially useful in measuring salivary gland function in patients with common autoimmune disorders. The main advantage of gustatory stimulation is reduction in the variability of salivary flow rates among study subjects [4]. Several studies have been conducted on the role of oral fluids (namely saliva and gingival crevicular fluid) in viral hepatitis. However, no conclusive results have been obtained on the role of oral fluids in the transmission or diagnosis of viral hepatitis, its progress, or treatment monitoring. Further studies are required to assess the variations in the levels of oral fluid secretion in patients with viral hepatitis. If such changes can be proven, it might help identify why the rate of dental caries is significantly higher in patients with HCV infection than in the general population [5]. We suggest that randomized controlled trials and experimental observations, including salivary gland function monitoring before and after treatment, to be conducted in HCV-infected patients. Evaluating the presence of HCV in salivary gland tissues could also yield accurate results.

The association of infection and clinical severity in sickle cell anaemia patients

Sickle cell anaemia (SCA) patients have a high risk of infection. We retrospectively investigated the prevalence of infection among SCA patients from Bahia, Brazil. A total of 1415 SCA patients were studied between 1995 and 2009: 190 (13.4%) had hepatitis C virus (HCV), 67 (4.7%) had human T-lymphotropic virus type I (HTLV-I), 44 (3.1%) had hepatitis B virus (HBV), 40 (2.8%) had Chagas' disease, 11 (0.8%) had human immunodeficiency virus (HIV), and 5 (0.4%) had syphilis. Patients with HCV infection had a higher risk of hospitalisation (OR=1.52, 95% Cl: 1.07-2.17, P=0.020), bone disorders (OR=1.94, 95% Cl: 1.15-3.27, P=0.011), stroke (OR=2.17, 95% Cl: 1.12-4.14, P=0.017), painful crisis (OR=1.61, 95% Cl: 1.17-2.22, P=0.004) and leg ulcers (OR=1.61, 95% Cl: 1.04-3.03, P=0.031). Patients with HBV infection had a higher risk for bone disorders (OR=4.90, 95% Cl: 2.08-11.54, P<.010), stroke (OR=3.01, 95% Cl: 1.29-6.04, P=0.007), painful crisis (OR=3.51, 95% Cl: 1.62-7.63, P<0.001), acute chest syndrome (ACS) (OR=2.66, 95% Cl: 1.34-5.28, P=0.004), leg ulcers (OR=6.60, 95% Cl: 3.37-12.91, P<.001) and vaso-occlusive crisis (OR=6.34, 95% Cl: 1.96-20.66, P<0.001). Patients with HTLV-I infection had a high risk for bone disorders (OR=2.94, 95% Cl: 1.28-6.74, P=0.011), respiratory failure (OR=2.66, 95% Cl: 1.26-5.51, P=0.012), leg ulcers (OR=3.27, 95% Cl: 1.69-6.11, P<.001), painful crisis (OR=1.82, 95% Cl: 1.07-3.13, P=0.025) and ACS (OR=1.85, 95% Cl: 1.10-3.41, P<.047). SCA patients with HCV infection had increased triglycerides and low-density lipoprotein cholesterol (P=0.036; P=0.027), iron serum (P=0.016) and ferritin (P=0.007). These results reveal important roles for these infections in SCA patients' clinical outcomes, and studies are warranted to determine the mechanisms utilised by these agents and their involvement in disease severity.

A population-based cohort study for the risk factors of HCC among hepatitis B virus mono-infected subjects in Japan

There have only been a few prospective studies investigating risk factors associated with the development of hepatocellular carcinoma (HCC) among chronic hepatitis B patients all over the world, and no study has been conducted in Japanese population. A population-based cohort consisting of 19393 subjects (middle aged or older) with over 13 years' follow-up was investigated in Japan. Of 19393 subjects, 479 had hepatitis B virus (HBV) mono-infection (2.5%). During the 245923 person-years' follow-up (average follow-up period 12.7 years), 13 cases of newly diagnosed HCC were documented in the HBV mono-infected group. Several factors at baseline (male, smoking, alanine aminotransferase, the positivity of HBe antigen and HB core-related antigen, the proportion of HBV DNA ≥ 5 log copies/mL, T1753V mutation, and A1762T/G1764A double mutation) were significantly associated with HCC among HBV mono-infected subjects. Multivariate-adjusted Cox hazard model showed that A1762T/G1764A (hazard ratio 7.05 [95% confidence interval (CI) 1.03-48.12, P = 0.046]) was the only independent risk factor for the development of HCC. Kaplan-Meier method also showed that the probability of HCC occurrence-free was significantly lower in HBV mono-infected subjects with A1762T/G1764A double mutation than those without these mutations. HBV mono-infected subjects with A1762T/G1764A double mutation could be at high risk of HCC development during the natural course of HBV infection.

Association of uraemic pruritus with inflammation and hepatitis infection in haemodialysis patients

Chronic inflammation and hepatitis C virus (HCV) infection have been implicated in the pathogenesis of uraemic pruritus in haemodialysis (HD) patients. However, each one's independent roles have not been previously studied. A total of 321 HD patients diagnosed with end-stage renal disease with maintenance HD for >3 months were included. A visual analogue scale (VAS) was used to subjectively measure the severity of itching. Based on the VAS score, patients were divided into three groups: Group 1, no pruritus (VAS = 0); Group 2, mild to moderate pruritus (VAS 0-5) and Group 3, severe pruritus (VAS >5). There were 120 (37.4%) patients without any pruritus, 141 (43.9%) with mild to moderate pruritus and 60 (18.7%) with severe pruritus. Forty-six (14.3%) had hepatitis B virus (HBV) infection and 37 (11.5%) had hepatitis C virus (HCV) infection. The average serum high-sensitivity C-reactive protein (hsCRP) level was 0.58 mg/dl. Patients with severe pruritus had a significantly higher serum hsCRP level and more HBV or HCV infection (all P < 0.05). In the multi-variable logistic regression model, higher levels of hsCRP (OR = 3.54, P = 0.008) and HCV infection (OR = 2.77, P = 0.014) were both significant independent predictors for severe pruritus. Our study demonstrated the heavy burden of pruritus in HD patients and corroborated the role of inflammation in the pathogenesis of uraemic pruritus. HCV infection is associated with severe uraemic pruritus but is independent of the serum hsCRP level in HD patients.

Dissecting out crytogenic liver disease

See article on page 429 The report from Pamplona in this issue of Gut 1 gives insight into the spectrum of liver disease in Southern Europe and emphasises the importance...

The threat of hepatitis B virus recurrence: A sword of damocles to the liver transplant recipient

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanined by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in the native liver increased the risk of HBV induced tissue damage in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function. Four patients who underwent transplantation for hepatitis B virus-related liver disease developed rapidly progressive liver failure attributable to recurrent hepatitis B disease typified by hyperbilirubinemia and distinctive hepatocyte ballooning and progressive fibrosis consistent with recently reported fibrosing cholestatic hepatitis. Among these four patients, the mean interval from transplantation to redocumentation of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) was 5 months, to development of malaise and jaundice 6 months, to histological diagnosis 7 months, and to graft failure 8 months. the only patient who underwent retransplantation had accelerated recurrence of the same syndrome with biopsy documentation 1 month later and graft failure 2 months. Distinctive histological features included confluent hepatocelular balloning and progressive periportal fibrosis followed by lobular collapse over 4-6 weeks without significant inflammation. Immunohistochemical staining showed marked HBsAg and hepatitis B core antigen (HBcAg) immunoreactivity. The rapid development of cytolytic hepatocellular necrosis and lobular collapse with promient HBcAg immunoreactivity without significant inflammation suggests a cytolytic rather than immune pathogenesis for this unique and devastating form of recurrent hepatitis B that might better be termed “fibrosing cytolytic hepatitis”.

High prevalence of viral infection in adults with homozygous and heterozygous alpha 1-antitrypsin deficiency and chronic liver disease.

To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) alpha 1-antitrypsin deficiency and to assess the presence of other possible risk factors for the development of chronic active hepatitis and cirrhosis of the liver in these patients. Cross-sectional study. A referral-based university hospital. Consecutive patients (164) with the Pi ZZ and Pi Z phenotype with and without chronic liver disease. The presence of antibody to hepatitis C virus (anti-HCV) was determined using an assay incorporating synthetic peptide antigen from capsid protein (United Biomedical [UBI] assay) and a second-generation enzyme immunoassay (Abbott test); the presence of antibody to hepatitis B virus (anti-HBV) was determined using radioimmunoassays incorporating hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg); assays for antinuclear antibody and antimitochondrial antibody (M2 subtype) were also done, and alcohol abuse was assessed by history. Among patients with cirrhosis (32%), 62% were anti-HCV positive by the Abbott test (P = 0.006), and 41% were anti-HCV positive by the UBI assay (P = 0.007). Thirty-three percent of patients with cirrhosis had hepatitis B virus (HBV) infection (P = 0.01); 41% had a history of alcoholism; and 12% had features of autoimmune liver disease. Only five patients (9%) with cirrhosis had no other risk factor for chronic liver disease. Among patients with chronic active hepatitis (7%), 80% were anti-HCV positive by the Abbott test (P = 0.002), and 75% were anti-HCV positive by the UBI assay (P less than 0.001). Thirty percent of patients with chronic active hepatitis had HBV infection (P = 0.023); 18% had autoimmune hepatitis; and 8% abused alcohol. Only two patients (17%) had no additional risk factor for the development of chronic active hepatitis. Among patients with steatosis of the liver (48%), 5% were anti-HCV positive by the Abbott test, and none were anti-HCV positive by the UBI assay; 18% had serologic evidence of past HBV infection, and 28% abused alcohol. Among patients without chronic liver disease (13%), no viral infection could be found; 9% were alcoholics. Chronic liver disease in patients with alpha 1-antitrypsin deficiency is associated with a high prevalence of viral infection; this infection, rather than alpha 1-antitrypsin deficiency alone, may be the cause of the liver disease in such patients.

Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation.

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function.