Hepatitis B Virus Related Liver Disease Research Articles

Reprogramming of lipid metabolism in hepatocellular carcinoma resulting in downregulation of phosphatidylcholines used as potential markers for diagnosis and prediction

ABSTRACT Background Aberrant methylation and metabolic perturbations may deepen our understanding of hepatocarcinogenesis and help identify novel biomarkers for diagnosing hepatocellular carcinoma (HCC). We aimed to develop an HCC model based on a multi-omics. Research design and methods Four hundred patient samples (200 with HCC and 200 with hepatitis B virus-related liver disease (HBVLD)) were subjected to liquid chromatography-mass spectrometry and multiplex bisulfite sequencing. Integrative analysis of clinical data, CpG data, and metabolome for the 20 complete imputation datasets within a for-loopwas used to identify biomarker. Results Totally, 1,140 metabolites were annotated, of which 125 were differentially expressed. Lipid metabolism reprogramming in HCC, resulting in phosphatidylcholines (PC) significantly downregulated, partly due to the altered mitochondrial beta-oxidation of fatty acids with diverse chain lengths. Age, sex, serum-fetoprotein levels, cg05166871,cg14171514, cg18772205, PC (O-16:0/20:3(8Z, 11Z, 14Z)), and PC (16:1(9Z)/P-18:0) were used to develop the HCC model. The model presented a good diagnostic and an acceptable predictive performance. The cumulative incidence of HCC in low- and high-risk groups of HBVLD patients were 1.19% and 21.40%, respectively (p = 0.0039). Conclusions PCs serve as potential plasma biomarkers and help identify patients with HBVLD at risk of HCC who should be screened for early diagnosis and intervention.

Time-trends in disease characteristics and comorbidities in patients with chronic hepatitis B in the period 1980–2020

Background & aimsThe incidence of chronic hepatitis B (CHB) is declining due to successful implementation of vaccination programs and widespread use of antiviral therapy. We aimed to study time-trends in disease characteristics and comorbidities in newly referred CHB patients. MethodsWe collected information on hepatitis B virus (HBV) related disease characteristics (including hepatitis B e-antigen (HBeAg) status, viremia, stage of liver fibrosis and indication for treatment and/or hepatocellular carcinoma (HCC) surveillance) and presence of comorbidities in all CHB patients referred to our center from 1980 through 2020. Patient characteristics were compared according to referral date (before 2000, between 2000 and 2010 and after 2010). ResultsWe identified 1515 eligible patients. Patients referred after 2010 were older (36 versus 34 years, p < 0.001), more often non-Caucasian (82.3% versus 55.0%, p < 0.001) and more frequently HBeAg negative (81.5% versus 49.8%, p < 0.001) when compared to patients referred before 2000. Adjusted for ethnicity, sex and age, patients referred after 2010 were less likely to have significant fibrosis (adjusted odds ratio [aOR]:0.178, p < 0.001) or indication for antiviral therapy (aOR:0.342, p < 0.001) but were more likely to be affected by the metabolic syndrome (aOR:1.985, p = 0.013), hepatic steatosis (aOR:1.727, p < 0.001) and metabolic dysfunction associated fatty liver disease (MAFLD) (aOR:1.438, p = 0.013). ConclusionsThe characteristics of the CHB populations are changing. Newly referred patients are older, have less active HBV related liver disease but are more likely to be co-affected by MAFLD. These findings provide guidance for adequate allocation of resources to cope with the changing characteristics of the CHB population. FundingFoundation for Liver and Gastrointestinal Research Rotterdam, the Netherlands and Gilead Sciences

Association of PD-L1 gene polymorphisms and circulating sPD-L1 levels with HBV infection susceptibility and related liver disease progression.

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n=186), liver cirrhosis (LC, n=142) and hepatocellular carcinoma (HCC, n=223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR=1.6; 95%CI=1.1-2.3; p=0.0087) and disease progression (LC vs. CHB: OR=1.8; 95%CI=1.1-2.9; p=0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p<0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C>B>A, p<0.0001) and BCLC classification (BCLC D>C>B>A, p=0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.

Distinctive pattern of AHNAK methylation level in peripheral blood mononuclear cells and the association with HBV-related liver diseases.

The purpose of this study was to investigate the correlation between AHNAK methylation level in peripheral blood mononuclear cells (PBMC) and the progression of hepatitis B virus (HBV)‐related liver disease. Bioinformatics methods were applied to evaluate the AHNAK methylation level in PBMC and T cells at different stages of HBV related liver disease, to investigate the correlation between AHNAK methylation and clinical features, as well as to compare the methylation site of AHNAK in cancer tissues and adjacent tissues. Subsequently, the differentially expressed gene analysis technique was used to analyze the liver disease‐related genes and immune‐related pathways in hepatitis B patients with different pathological changes. Finally, promoter methylation and mRNA expression of AHNAK gene in liver cancer and adjacent tissues were determined by quantitative polymerase chain reaction (Q‐PCR), and the diagnostic value of AHNAK methylation level in hepatopathy was evaluated by receiver operating characteristic (ROC) curve. The promoter methylation level of AHNAK gene in PBMCs decreased with the progression of HBV‐related liver disease, and showed significant difference among the patients with various HBV‐related liver diseases (P = 0.0001). The AHNAK methylation level in PBMCs and T cells was negatively associated with age, white blood cell count, CREA, drinking, and positively associated with APTT and HbsAg. Higher mRNA expression of AHNAK was found in liver cancer tissues than that of adjacent tissues (P < 0.001), and the methylation level in PBMC decreased with the progression of hepatitis B‐related liver disease. The area under the ROC curve (ROC) was 0.883 (P < 0.001) in diagnosis of chronic hepatitis B (CHB), 0.885 (P < 0.001) in diagnosis of compensatory liver cirrhosis, 0.955 (P < 0.001) in diagnosis of decompensated liver cirrhosis, 0.981 (P < 0.001) in diagnosis of hepatocellular carcinoma. Our results revealed that AHNAK methylation level in peripheral blood decreases with the progression of hepatitis B‐related liver disease. This provided a potential differential diagnostic method for HBV‐related hepatopathies, and thus an early detective tool for liver cancer.

Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and clinical relevance.

The Hepatitis B Virus (HBV) has a worldwide distribution and is endemic in many populations. It is constantly evolving and 10 genotypic strains have been identified with varying prevalences in different geographic regions. Numerous stable mutations in the core gene and in the surface gene of the HBV have also been identified in untreated HBV populations. The genotypes and viral variants have been associated with certain clinical features of HBV related liver disease and Hepatocellular carcinoma. For example Genotype C is associated with later hepatitis B e antigen (HBeAg) seroconversion, and more advanced liver disease. Genotype A is associated with a greater risk of progression to chronicity in adult acquired HBV infections. Genotype D is particularly associated with the precore mutation and HBeAg negative chronic hepatitis B (CHB). The genotypes prevalent in parts of West Africa, Central and South America, E, F and H respectively, are less well studied. Viral variants especially the Basal Core Promotor mutation is associated with increased risk of fibrosis and cancer of the liver. Although not currently part of routine clinical care, evaluation of genotype and viral variants may provide useful adjunctive information in predicting risk about liver related morbidity in patients with CHB.

Overview of hepatitis B prevalence, prevention, and management in the Pacific Islands and Territories.

There are over 500-750 000 deaths per year because of hepatitis B virus (HBV)-related cirrhosis and liver cancer worldwide and the World Health Organization Western Pacific Region has some of the highest endemic levels of HBV in the world, particularly within China, South East Asia and Pacific Island Countries and Territories (PICT). The PICT have unique ethnic diversity and a very high prevalence of smoking and metabolic syndrome, both important risk factors for liver fibrosis and liver cancer. However, in contrast to many Asian countries, there is little published data on HBV prevalence and related liver disease burden in PICT. In this review, the available published literature and World Health Organization data for HBV prevalence and related liver disease and liver cancer burden in PICT is outlined, and unmet needs for improving HBV prevention and control in the region are highlighted.

Dynamics and liver disease specific aspects of quality of life among patients with chronic liver disease in Yunnan, China.

Patients with chronic liver diseases (CLD) may have compromised health related quality of life (HRQoL). Hepatitis B virus (HBV) infection has long been the leading cause of CLD including liver cancer and cirrhosis. Knowledge on different symptom profiles of CLD should help in development of comprehensive treatment and patient care plans. To access the facets of HRQoL in chronic liver diseases throughout their spectrum of severity. A cross-sectional study was conducted in the First Affiliated Hospital of Kunming Medical University in Yunnan Province of China. Both out- and inpatients undergoing treatment protocols for different HBV related liver disease states were consecutively collected from December 2012 to June 2013. ANOVA was used to compare the mean scores of EQ-5D and chronic liver disease questionnaire (CLDQ) among 5 disease groups. The relationship between demographic variables predicting global CLDQ scores and the domains of CLDQ was analysed. A total of 1040 patients including 520 without complications, 91 with compensated cirrhosis, 198 with decompensated cirrhosis, 131 with HCC and 100 with liver failure were recruited. All domains of CLDQ, the means of EQ-5D value and EQ VAS exhibited significant decline with worsening of disease severity from uncomplicated HBV to liver failure. The multivariate regression demonstrated the reduction of mean scores of CLDQ domain at advanced stage. Patients with liver failure and HCC had more HRQoL impairment than other disease states. No effect of patient gender was found. Patient age was associated with 'fatigue' and 'worry' domains (p=0.006; p=0.004) but not with other domains and global scores of CLDQ and ED-5D. The HRQoL in chronic hepatitis B patients is greatly affected by disease states. Care for HBV-related diseases should consider not only the outcomes of treatment strategies but also improvement in patient wellbeing.

Anti-HBc–positive/HBsAg-negative liver donors pose a higher risk of occult HBV infection but do not cause severe histological damage in liver grafts

The use of serum anti-hepatitis B core antibody (HBc)-positive/hepatitis B surface antigen (HBsAg)-negative liver donors for patients with hepatitis B virus (HBV)-related liver disease (HBRLD) is a promising means of expanding the organ donor pool and does not increase the risk of HBV recurrence. However, whether such donors will compromise the histology of the liver grafts is unclear. Among 84 patients who underwent transplantation for HBRLD and who did not have post-transplant HBV recurrence (non-detectable serum HBsAg and HBV DNA), 19 underwent liver biopsy (eight received anti-HBc-positive/HBsAg-negative liver grafts; 11 received anti-HBc-negative liver grafts) and were included in the study. Intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) were detected using real-time polymerase chain reaction; histological characteristics were evaluated with the Batts-Ludwig semi-quantitative scoring system. Of the 19 recipients, nine (47.4%) were positive for intrahepatic HBV DNA; 82.5% (7/8) received grafts from anti-HBc-positive donors and 18.2% (2/11) received grafts from anti-HBc-negative donors (P=0.003). HBV cccDNA was not detectable in the liver grafts of the 19 recipients. Ten patients had mild inflammation and minimal fibrosis in the portal area: four of the eight in the anti-HBc-positive group and six of the 11 in the anti-HBc-negative group (P>0.05). Anti-HBc-positive/HBsAg-negative donors for HBRLD pose a higher risk of occult HBV infection post-liver transplant but do not cause liver damage. Thus, anti-HBc-positive grafts may be considered an effective and safe means of expanding the pool of liver donors for patients with HBRLD.

RANTES Promoter Gene Polymorphism and its Association with HBV Related Liver Disease

Background: Immune-mediated mechanisms have been found to play important role in the progression of hepatitis B virus (HBV) infection. Chemokines are a group of chemotactic molecules that specifically attract and recruit populations of immune effector cells to the sites of injury or infection. Their major role is in leukocyte migration and dependent processes such as immune surveillance and innate and adaptive immune responses. Regulated and normal T-cell expressed and secreted (RANTES) may have a role in the selective recruitment of T-cells to portal and periportal regions in liver during inflammation.

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus (HIV) positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers. Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients co-infected with hepatitis B virus (HBV). However, liver transplantation in HIV positive patients with hepatitis C virus (HCV) has poorer outcomes overall, requiring careful selection of candidates. This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management. In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.

Genetic polymorphisms of CYP2E1 and DNA repair genes HOGG1 and XRCC1: Association with hepatitis B related advanced liver disease and cancer

A population based case–control study was designed to explore the genetic risk factors for hepatitis B virus (HBV) related liver disease susceptibility. A total of 424 subjects comprising 210 controls, 50 acute HBV (AVH), 84 chronic HBV (CHBV), 25 HBV related cirrhosis and 55 HBV related hepatocellular carcinoma (HCC) cases were included in the study. PCR-RFLP was used for the genotyping of Cyp2E1*5B, hOGG1 codon 326 and XRCC1 codon 399. Compared to controls, Cyp2E1 rsaI variant c2 genotype increased the risk of HBV related liver disease severity by 2.68 fold, the highest for HCC cases (3.981 folds, p=0.106); and was associated with higher histology activity index (HAI) (p<0.001) in CHBV patients. Cyp2E1 and hOGG1 variants were independently associated with a significantly higher fibrosis score in CHBV group. Analysis of gene–gene interaction studies showed an increased risk of HCC, cirrhosis and CHBV in a Cyp2E1 variant+XRCC1 variant combination (p<0.001); and hOGG1 variants+XRCC1 variants. A mutually independent heterozygous hOGG1 and XRCC1 combination resulted in a decreased risk of HBV related liver disease. On the other hand, a wild-type hOGG1 and XRCC1 combination was associated with a significantly higher risk of AVH (p=0.010) but a lower risk of CHBV (p=0.032) and HCC (p=0.006). The gene–gene interactions were also associated with a significant increase in HAI and fibrosis score in CHBV patients. Cyp2E1, hOGG1 and XRCC1 genotypes significantly alter the risk of HBV related liver disease susceptibility and severity, independently or through gene–gene interaction.

Is There Any Value to Hepatitis B Virus Genotype Analysis?

Hepatitis B may cause a varying spectrum of diseases ranging from an asymptomatic or mild anicteric acute illness, to severe or fulminant hepatitis. Similarly, the outcome of chronic hepatitis B is variable. Viral factors associated with outcome of chronic hepatitis B virus (HBV) infection include hepatitis B e antigen status, HBV DNA, genotype, and HBV variants. HBV genotypes and subgenotypes have been associated with differences in clinical and virological characteristics, indicating that they may play a role in the virus-host relationship. A total of ten hepatitis B virus genotypes have been defined with a distinct geographical distribution. Hitherto, genotypes A, B, C and D have been studied most extensively. The HBV genotype appears to influence not only the natural history of HBV related liver disease but also the response to HBV treatment. HBV genotypes are also linked with both core promoter and BCP mutations. Progression to chronic infection appears to occur more frequently following acute infection with genotypes A and D than with the other studied genotypes. Genotypes A and B appear to have higher rates of spontaneous HBeAg seroconversion. More advanced liver disease and progression to HCC is more often seen in chronic infection with genotypes C and D in contrast to genotypes A and B. More specifically, genotypes A1, C, B2-B5 and H appear to be associated with more serious complications than genotypes A2, B1 and B6. These observations suggest important pathogenic differences between HBV genotypes. Genotypes A and B have higher response rates to interferon based therapy than genotypes C and D. Knowledge of HBV genotype enables clinicians to identify those patients at increased risk of disease progression whilst aiding the selection of appropriate antiviral therapy. Genotyping and monoclonal subtyping can provide useful information for epidemiological studies. In conclusion, genotyping of chronic HBV infections can help practicing physicians identify those at risk of disease progression and determine optimal anti-viral therapy.

The relationship between hepatocellular carcinoma recurrence and hepatitis B virus recurrence after liver transplantation

To investigate the relationship between hepatocellular carcinoma (HCC) recurrence and hepatitis B virus (HBV) recurrence. The clinical data of 340 patients underwent liver transplantation due to HBV related end-stage liver disease and received long-term follow up in our hospital from Jan 2004 to Dec 2008 were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list and nucleoside analogues combined low-dose HBIG therapy during and after transplantation. Patients were regularly followed up at the outpatient, monitoring the HBV recurrence and survival. Multivariate Cox regression analysis was used to evaluate the risk factors for hepatitis recurrence. 33 patients suffered from HBV recurrence post transplantation. The 1-, 3- and 5- year recurrence rates were 7.0%, 10% and 13% respectively. The median HBV recurrence time was 5 months (1-21 months). COX regression analysis revealed that risk factors for HBV recurrence were HCC (HR = 2.98; 95% CI 1.08-8.25; P < 0.05) and pre-transplantation HBV-DNA load over 5 log10 copies/ml (HR = 3.99; 95% CI 1.85-8.62; P < 0.01). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which were 27.9% and 8.7% (HR = 4.58;95% CI 1.88-11.12; P < 0.01) respectively. 12 patients suffered from both HCC and HBV recurrence. Spearman correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times (r = 0.583, P < 0.05). Post transplantation HCC recurrence is a risk factor for HBV recurrence.

Prevention of HBV recurrence after liver transplant: The role of combination therapy

The prognosis after liver transplantation is related to the efficacy of prophylaxis of hepatitis B virus (HBV) graft re-infection. The risk of HBV re-infection is directly related to HBV viral load at the time of transplantation. HBV prophylaxis after transplantation with long-term administration of hepatitis B immunoglobulins (HBIG) or monoprophylaxis with lamivudine can significantly reduce the risk of HBV recurrence. Antivirals can control HBV replication in patients with decompensated HBV cirrhosis awaiting transplantation. However, there is a risk of HBV viral breakthrough during nucleo(t)side antiviral treatment. Efficacy of antivirals and the risk of viral resistance should be taken into account. The post-transplant combination of antiviral therapy and HBIG prophylaxis is very effective in reducing the rate of HBV re-infection to less than 10%, increasing the survival rate. The current 5-year survival after transplantation for HBV related liver disease is 85%. In patients without active viral replication at transplantation, the possibility of discontinuing HBIG prophylaxis over the long-term after transplantation with maintenance of antiviral treatment or HBV vaccination is under evaluation. In conclusion, the prophylaxis of HBV re-infection combining antiviral therapy prior to transplantation, and combination of HBIG and antiviral therapy post-transplantation is effective in reducing the rate of HBV re-infection.

Prevention and management of hepatitis B virus reinfection after liver transplantation

To investigate the prevention and treatment of hepatitis B virus (HBV) reinfection and recurrence after orthotopic liver transplantation (OLT) for HBV related end-stage liver disease. The clinical data of 316 patients undergoing allograft orthotopic liver transplantation who lived more than 6 months and had HBV infection preoperative with complete data from March 2001 to March 2007 at the First Affiliated Hospital of Sun Yat-sen University. According to the HBV prevention strategy, these patients were divided into two groups: group with pure lamivudine (LAM) (n = 106) and group with lamivudine plus intramuscular injection of low dose anti-hepatis B immunoglobulin (HBIG) (n = 210). Mean follow-up was 33.6 months. The rate of HBsAg negative conversion 1 week after OLT of the LAM group was 82.1% (87/106), significantly lower than that of LAM + HBIG group [91.0% (191/210), P < 0.05]. The rates of HBV reinfection, HBV recurrence, and YMDD mutation of the lamivudine group was 17.0% (18/106), 11.3% (12/106) and 8.5% (9/106) respectively, all significantly higher than those of LAM + HBIG group [6.2% (13/210), 3.8% (8/210) and 2.4% (5/210) respectively, P < 0.05 respectively]. All patients with HBV reinfection or HBV recurrence were treated with Adefovir, Entecavir or increased dose of HBIG and achieved better curative effect. The therapy with high dose of HBIG combining with adefovir or entecavir is better for patients who have HBV reinfection. Patients with HBV recurrence after OLT should be administrated reasonable liver aid, immunity regulation and anti-hepatic fibrosis to obtain better transplant liver histological results and normal transplant liver function.

Prevention and treatment of hepatitis B recurrence after liver transplantation

To investigate the effect of the regimen of lamivudine (LAM) combined with hepatitis B immunoglobulin (HBIG) in prevention and treatment of re-infection of hepatitis B virus (HBV) and recurrence of hepatitis B after orthotopic liver transplantation (OLT) for HBV related end stage liver disease. The clinical data of 183 adult liver transplantation patients who lived more than 6 months and were followed up for 14.6 months with complete data were studied retrospectively. According to the HBV prevention strategy, these recipients were divided into two groups: group of pure LAM (n = 106) and group of LAM plus intramuscular injection of low dose HBIG (n = 77). The rate of HBsAg negative conversion 1 week after OLT of the LAM group was 82.10% (87/106), significantly lower than that of the LAM + HBIG group [94.81% (73/77), P = 0.010]. The rates of HBV reinfection, HB recurrence, and YMDD mutation of the lamivudine group were 16.98% (18/106), 11.32% (12/106), and 8.49% (9/106) respectively, all significantly higher than those of the LAM + HBIG group [6.49% (5/77), 2.60% (2/77), and 1.30% (1/77) respectively, P = 0.035, 0.028, and 0.035 respectively]. All the patients with YMDD mutation were treated with adefovir (ADF) with improvement. Analysis showed no obvious difference in the effect of LAM given intramuscularly or intravenously. The protocol of combination of LAM and HBIG is highly effective, safe, and cost-effective in preventing the recurrence of HBV after OLT. YMDD mutation can be treated by ADF with satisfactory results.

Hepatitis B Virus Genotypes in Saudi Arabia

Purpose: Hepatitis B virus (HBV) infection has a wide spectrum of liver diseases, ranging from acute or fulminant hepatitis, chronic hepatitis, and cirrhosis to hepatocellular carcinoma. Recently, HBV genotypes have attracted increasing attention as they may affect the disease progression and outcomes of HBV related chronic liver disease, as well as to response to antiviral therapies. It has been reported that different hepatitis B virus (HBV) genotypes has distinct geographic distribution. Genotype A is prevalent in northern and central Europe, but it is also common in North America and sub Saharan Africa. Genotypes B and C are confined to Asia. Genotype D is widespread, but it is the predominant genotype in the Mediterranean region, while genotype E is found mainly in West Africa. Genotype F shows the highest divergence among the genotypes and is indigenous to aboriginal population of the America. The newly described genotype G has been found in USA and France. We aimed to study the prevalence of HBV genotypes in Saudi Arabia since there are no published data as well as to look for any association between different HBV genotypes with Alanine aminotransferases (ALT), Hepatitis B surface antigen (HBsAg), Hepatitis B e antigen (HBeAg) and HBV viral load. Methods: Between January 2004 to December 2005, 912 HBV PCR positive serums were collected from Saudi patients and from this pool fifty-eight samples were selected randomly for HBV genotyping by INNO-LiPA (a line probe assay). Association between genotypes and HBsAg, HBeAg, ALT and viral load were tested using chi square test using SPSS version 11. Results: Their mean age was 38.9 years (range 5–73 years) and 44 (76%) of them were male. Out of the 58 patients tested for HBV genotyping, 50 (86.2%) were HBV genotype D; three were genotype A (5.2%), three genotype E and two (3.4%) genotype A/D (mixed). There was no association between genotypes with ALT, HBsAg, HBeAg and viral load (p value >0.05). Conclusions: HBV genotype D was found to be the commonest genotype prevalent in Kingdom of Saudi Arabia and there was no significant association between different HBV genotypes with ALT, HBsAg, HBeAg or viral load. HBV genotype E was detected in small percentage of cases.

Prevention and treatment of hepatitis B virus reinfection after liver transplantation

To investigate the risk factors and treatment of hepatitis B virus (HBV) reinfection after liver transplantation. Patients with HBV related end-stage liver disease underwent liver transplantation in our center, and received the combination of intramuscular hepatitis B virus immunoglobulin and oral lamivudine as prophylaxis for HBV reinfection. HBV reinfection cases were monitored after the transplantation. HBsAg disappeared and HBsAb was detectable in 128 of total 130 patients. The median follow-up period was 12.2 months after transplantation. Eight patients developed HBV reinfection. The recurrence rate of HBV was 6.3%. The reinfection risks were 14.3% and 4.0% respectively among patients with serum HBeAg positive and negative before transplantation (P < 0.05). Among patients with serum HBsAg positive and negative at the first day after liver transplantation, the reinfection risks were 21.1% and 3.7% respectively (P < 0.05). Combination of intramuscular HBIg and Lamivudine as prophylaxis of HBV reinfection is effective. HBeAg positive before liver transplantation and HBsAg positive at the first day after transplantation are risk factors of HBV reinfection.

Delta agent infection in acute hepatitis and chronic HBsAg carriers with and without liver disease.

Hepatitis B virus (HBV) is a major cause of chronic liver disease in southern Italy. In the same area superinfection with the delta agent is endemic. To assess the prevalence of delta infection in a large population of patients with acute and chronic HBV related liver disease and to look for differential features among delta infected and uninfected subjects sera from 592 consecutive HBsAg positive patients were tested for the delta/anti-delta system by RIA. In no case was delta Ag found in serum. The prevalence of anti-delta was low in acute hepatitis (6.6%) and in asymptomatic carriers (6.4%) but raised in chronic active hepatitis with or without cirrhosis (52.3%). A decrease in frequency of anti-delta was seen in inactive cirrhosis (38.8%) and in hepatocellular carcinoma (11.9%). A younger mean age of delta-infected subjects was observed in each type of chronic liver disease. Our data confirm that delta agent superinfection is definitely associated with severe chronic active liver disease. The difference in age between anti-delta positive and negative patients suggests that delta infection accelerates the natural history of HBV related liver disease.