Cause Of Chronic Hepatitis Research Articles

Interleukin one beta (IL-1B) gene polymorphisms in Iraqi patients with susceptibility to develop hepatitis C infections

Hepatitis C virus (HCV) infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide. Initial exposure to HCV is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus. This study aimed to find an associated relationship between HCV susceptibility and Polymorphic gene of IL‐1B targeting a total of 45 individuals: 30 patients with chronic hepatitis C and 15 healthy control from different cities of Iraqi recruited the Hospital for diseases of the digestive system and liver in Baghdad between November 2022 to February 2023. Genomic DNA was extracted and specific promotor sequence was amplified by polymerase chain reaction (PCR) followed by sequencing then measuring serum concentrations of IL-1β by Enzyme-Linked Immunosorbent Assay (ELISA). The results revealed significant difference in serum levels of IL-1B (P≤0.01), from 1.10-+0.09 in Chronic HCV patients in comparison with its level in healthy controls 7.58± 0.28. Molecular results suggested that single nucleotide polymorphisms in the promoter of IL-1B is probably associated with susceptibility to HCV chronic infection according to this sample of Iraqi patients. In conclusion, the results suggested that variation in serum level and polymorphism in IL-1B is probably associated with susceptibility to hepatitis C virus chronic infection.

Co-relation of hepatitis C RNA load with antiviral therapy and risk factors among hepatitis C seropositive patients

Hepatitis C virus is a bloodborne virus and the major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Viral load is the prognostic marker of the disease progression. The aim of this study is to determine the correlation of hepatitis C RNA load with antiviral therapy and its risk factors among the HCV seropositive patients. This study will be helpful in early assessment of the disease progression and its complications.The blood samples were collected over a period of one year from April 2022-March 2023. The serum was subjected to ELISA for Anti HCV Ab. Viral load quantification was done by MylabPathoDetect HCV Quantitative PCR Kit in HCV seropositive patients.About 18,882 patients were tested for HCV infection over a period of one year. 75 patients were positive for HCV infection. Prevalence of HCV was 0.39. The mean viral load was reduced from 3.08×10 IU/ml to 1.98×10 IU/ml and Sustained Viral Response (SVR12) was achieved in 63(84%) patients after effective treatment with direct acting antiviral agents. High risk sexual behavior was the most common risk factor observed in seropositive patients.The current study determines the reduction in mean viral load and achieving sustained viral response after the effective antiviral therapy at the earliest, which is helpful in prevention of disease progression and its complications.

Molecular Characterization of Hepatitis B Virus among HIV Positive and HIV Negative Pregnant Antenatal Women in Federal Capital Territory Abuja Hospital

A significant contributor to chronic hepatitis, cirrhosis and hepatocellular carcinoma is the Hepatitis B Virus (HBV). Hepatitis B Virus (HBV) is a major cause of Chronic Hepatitis, cirrhosis and Hepatocellular Cancer (HCC). The incidence of HBV-related HCC cases is projected to increase for at least two decades due to the high prevalence of chronic HBV infection throughout the world. The overall aim of this study is to determine the sero-prevalence and molecular characterization of hepatitis B virus among HIV positive and HIV negative antenatal women attending Federal Capital Territory Abuja hospitals. A total number of 302 samples were collected from 302 participants between the ages of 18-55 years. The samples were screened for HIV, HBV, HBV serology markers, using rapid test kits, HBV Viral load and HBV genotyping was carried out using multiplex PCR method and data was analyzed using appropriate tools. Nine tested positive for HIV, 34 tested positive for HBV and 2 tested positive for both HIV and HBV, corresponding to 2.9 % (95% CI; 1.2 – 3.8) prevalence for HIV, 11.3% (95% CI; 8.7 – 13.6) for Hepatitis B and 0.7% for HIV/HBV co-infection. Age 25-35 years old had the highest prevalence of HBV 22(7.3%) followed by those of less than 25 years old 8(2.8%) and 1(0.7%) each for age range 36-45 years, 2(0.7%) and 46-55 years. HBeAb and HBcAb were expressed highest among subject within the age range of 25 – 35 year 14 (41.2%) and 22 (64.7 %,) participants respectively, followed by the age range of less than 25 years 5 (14.7%) and 8 (36.4%), for HBeAb and HBcAb respectively. There was no Hepatitis B envelop antigen (HBeAg) nor Hepatitis B surface antibody (HBsAb) among the study group. Of the 34 samples, 20 (62%) had undetectable viral load, while 14 (38%) had detectable viral load. Genotype E was three times more prevalent among those of 25 years old and above than those less than 25 years old detected (75% and 25%). However, genotype B/E mixed was more expressed (60% of cases) among those less than 25 years old, than those greater than 25 years of age (40%). There was no significant difference in the prevalence of genotype E and B/E serotype between HBV+/HIV-patients and their HBV+/HIV+ counterpart (P=0.08 and P=0.15, respectively). HBV Genotype E single infection viral load was significantly (P=0.01) more expressed among those 25 years of age and above than less than 25 years old (4,354,703 ± 346865 IU/ml versus 55.6 ±28.1 IU/ml). Mixed infection genotype B/E was significantly (P=0.04) more expressed among those less than 25 years of age than those 25 years old and above (730.9 ± 238 IU/ml versus IU/ml versus 91.1 ± 48 IU/ml). There was no significant difference between the mean of HBV Viral load HBV+/HIV- patients and their HBV+/HIV+ counterpart (T-test =0.009; P=0.92). In conclusion FCT is 11.3% prevalence rate of HBV and genotypes E and B/E are in circulation among pregnant women among the pregnant women attending antenatal clinic in FCT hospital in Abuja.

Prevalence and associated factors for hepatitis B infection among pregnant women attending antenatal clinic at SOS Hospital in Mogadishu, Somalia.

Hepatitis B virus (HBV) remains a leading cause of chronic hepatitis, maternal complications, and neonatal deaths in sub-Saharan Africa. Mother-to-child transmission is a major route of HBV transmission in endemic areas. This study aimed to determine the prevalence of hepatitis B infection and its associated factors among pregnant women attending Antenatal Care clinics at SOS Hospital in Mogadishu, Somalia. The research followed a cross-sectional design, and the participants were chosen through systematic random sampling, including every fifth outpatient. Each participant provided a blood sample for standard testing, and their consent was obtained before conducting Hepatitis B screening using the ELISA method. In our study of 384 pregnant women, 43 individuals (11.2%) tested positive for HBsAg. The frequency of HBsAg seropositivity was significantly higher in subjects with no education when compared to those with primary education (AOR = 0.1, 95% CI: 0.01-0.96, p = 0.046). Caesarian Section (AOR = 0.02, 95% CI: 0.004-0.0103, p = 0.001), blood transfusion (AOR = 11.6, 95% CI: 3.44-38.08, p = 0.001), previous dental procedures (AOR = 0.1, 95% CI: 0.04-0.38, p = 0.001), and unsafe injections in the past (AOR = 0.3, 95% CI: 0.09-0.91, p = 0.035) were identified as significant risk factors for hepatitis positivity. The study found a higher prevalence of hepatitis B compared to previous studies. Factors such as blood transfusion, dental procedures, Caesarian Section, and unsafe injections were associated with hepatitis B infection. It is essential to raise awareness, promote preventive measures, and implement routine screening for pregnant women so as to stop the transmission of hepatitis B to their children.

The combined pioglitazone and topiramate therapy for management of pediatric patients with severe MASLD.

Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults. Pioglitazone has been shown to improve liver histology in adult patients with MASLD, and in some studies, it attenuated liver fibrosis. Despite its perceived efficacy, pioglitazone is not widely used, likely due to its side effect profile, specifically increased weight gain. Topiramate lowers body weight in adolescents and in combination with phentermine, is one of the few FDA-approved medications for the management of obesity in children over 12 years of age. We performed a retrospective review of the outcomes in pediatric patients with severe MASLD, treated with the combined pioglitazone and topiramate therapy. Here, we report a case series of seven adolescents with severe MASLD and ≥F2 liver fibrosis treated with the combined pioglitazone and topiramate therapy. The combined therapy improved mean serum ALT from 165 ± 80 U/L to 89 ± 62 U/L after 12 months mean duration of treatment. One patient who completed 24 months of the combined therapy demonstrated a decrease in liver stiffness from 8.9 kPa to 5.6 kPa, as assessed by FibroScan elastography. There was a significant increase in body weight during this time, however, body mass index as a percentage of the 95 th percentile adjusted for age and gender did not increase significantly, 151 ± 29% vs. 152 ± 28%. Moreover, waist circumference, mid-upper arm circumference, percent body fat, and muscle mass were not significantly different before and after treatment. Serum lipid levels and hemoglobin A1c also did not change with the treatment. In summary, this case series provides encouraging results about the efficacy of the combined pioglitazone and topiramate therapy for the management of adolescents with severe MASLD, which should be further explored in clinical studies.

Leveraging metformin to combat hepatocellular carcinoma: its therapeutic promise against hepatitis viral infections

Hepatocellular carcinoma (HCC) is categorized among the most common primary malignant liver cancer and a primary global cause of death from cancer. HCC tends to affect males 2-4 times more than females in many nations. The main factors that raise the incidence of HCC are chronic liver diseases, hepatotropic viruses like hepatitis B (HBV) and C (HCV), non-alcoholic fatty liver disease, exposure to toxins like aflatoxin, and non-alcoholic steatohepatitis (NASH). Among these, hepatitis B and C are the most prevalent causes of chronic hepatitis globally. Metformin, which is made from a naturally occurring compound called galegine, derived from the plant Galega officinalis (G. officinalis ), has been found to exhibit antitumor effects in a wide range of malignancies, including HCC. In fact, compared to patients on sulphonylureas or insulin, studies have demonstrated that metformin treatment significantly lowers the risk of HCC in patients with chronic liver disease. This article will first describe the molecular mechanism of hepatitis B and C viruses in the development of HCC. Then, we will provide detailed explanations about metformin, followed by a discussion of the association between metformin and hepatocellular carcinoma caused by the viruses mentioned above.

Assessing the rate of non-linkage to care and identifying barriers in individuals living with hepatitis B. Results of the LINK-B study.

Hepatitis B infection is the most frequent cause of chronic hepatitis and liver cancer worldwide. Active searching for individuals with chronic hepatitis B has been proposed as a strategy to achieve the elimination of this virus. The primary aim of this study was to link to specialists HBsAg-positive individuals detected in a laboratory database and to characterize individuals who were not linked to care. We performed a retrospective-prospective evaluation of all HBsAg-positive serum samples identified in the central laboratory of the Northern Barcelona area between January 2018 and June 2022. After reviewing the patients' clinical charts, all those not linked to care were given an appointment with a specialist. Medical records of 2765 different HBsAg-positive serum samples were reviewed and 2590 individuals were identified: 844 (32.6%) were not linked to a specialist, 653 were candidates for linkage, and 344 attended the specialist visit. The two main reasons why they were not under specialist care were administrative issues, such as living in another region (12.1%) and lacking contact details (4.1%), and low life expectancy (2.8%). Individuals who did not attend their scheduled visit were mainly young [38.1 ± 12.9 vs. 44.0 ± 14.0 (p < .001)], non-White European [75.3% vs. 58.1% (p < .001)] and men [70.7% vs. 56.4% (p < .001)]. One in every three HBsAg-positive individuals in our setting was not currently under specialist care. Of particular note, half of them had never attended a specialist consultation, an essential step for evaluating the disease and starting therapy in some countries.

Purification of hepatitis C virus core protein in non-denaturing condition

Hepatitis C virus (HCV) is the major cause of chronic hepatitis and hepatocellular carcinoma. Among its structural proteins, the HCV core protein has been implicated in liver disease. Understanding the role of HCV core proteins in viral diseases is crucial to elucidating disease mechanisms and identifying potential drug targets. However, purification challenges hinder the comprehensive elucidation of the structure and biochemical properties of HCV core proteins. In this study, we successfully solubilized bacterially expressed core protein using a high-salt and detergent-containing buffer and bypassed the denaturing-refolding process. Size-exclusion chromatography revealed three distinct peaks in the HCV-infected cell lysate, with the bacterially expressed soluble core protein corresponding to its second peak. Using a combination of affinity, size exclusion, and multi-modal chromatography purification techniques, we achieved a purity of > 95% for the core protein. Analytical ultracentrifugation revealed monomer formation in the solution. Far UV Circular dichroism spectroscopy identified 25.53% alpha helices and 20.26% beta sheets. These findings strongly suggest that the purified core proteins retained one of the native structures observed in HCV-infected cells.

Hepatitis B Screening Program for patients attending out-patient department (OPD) at Sir Salimullah Medical College Mitford Hospital, Dhaka – An Observational Study

Background: Hepatitis B (HBV) is a major cause of chronic hepatitis, cirrhosis of liver and hepatocellular carcinoma in Bangladesh. It is also the most common cause of death from liver disease in the country. The prevalence of hepatitis B is 5-6% in the general population. So the present status of the virus is considered as an important public health concern of Bangladesh. Objectives: To investigate hepatitis B prevalence among the persons attending the OPD and to increase awareness about hepatitis B. Materials and methods: A cross-sectional observational study was carried out the at the Department of Hepatology, Sir Salimullah Medical College Mitford Hospital, Dhaka on March 17&amp;18, 2022 at Special Treatment Campaign on the occasion of celebration of the birth anniversary of the Father of Nation, Bangabandhu Sheikh Mujibur Rahman. A total of 190 people of both sexes from 18 years to 50 years of age group were enrolled in the study. These people were unaware of whether they were carrying hepatitis B virus or also was not aware of whether they are suffering from any kind of liver disease. Informed consent was taken and a pre-designed structured questionnaire was used. Screening was done by HBsAg detection using rapid diagnostic kit. Result: The mean age of respondents was 35.95±6.42 years with a male to female ratio of 0.83. Most of the respondents were married (72.63%) and Muslim (87.37%). Among them 47.36% of the respondents were service holders. Only 17.89% had a previous history of some types of hepatitis. 25.26% of respondents had history of different types of surgical procedure. 8 (4.2%) participants were found positive for HBsAg on the screening test in our study. Conclusion: This study shows 4.2 % of participants were screening positive among the respondents. This correlate with the intermediate prevalence of hepatitis B in Bangladesh as stated in World Health Organization data. Screening program increases knowledge and awareness among the population and thereby increase treatment seeking, which ultimately reduce incidence of disease and complications as well as death. Sir Salimullah Med Coll J 2023; 31: 3-8

Sero-prevalence of Hepatitis B virus infection among tribal under-five children in aspirational Nabarangpur district of Odisha, India

IntroductionHepatitis B (HB) is a major global health problem and a leading cause of chronic Hepatitis, liver cirrhosis, and hepatocellular carcinoma. Determining the prevalence of serological marker/s will help to know the burden of this disease and further carry out proper management. This study aimed to assess the seroprevalence of HBV infection among the tribal under-five children of Nabarangpur district, Odisha, India. MethodsA community based cross-sectional study was carried out employing multistage systematic random sampling. Serum samples were collected from 263 children. The participants were tested for Hepatitis B surface antigen (HBsAg) using Enzyme linked Immunosorbent Assay (ELISA). Descriptive statistics such as frequency and proportions were used to report the findings. ResultsWe observed 3 (1.14%) children to be positive for HBsAg. The prevalence of HBsAg was higher (1.63%) among females. ConclusionThe sero-prevalence of hepatitis B infection among under-five children was notably low in Nabarangpur district. This highlights the importance of vaccination coverage and further warrants information, education and communication to continue motivating people to uptake vaccines against the infection.

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis.

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus-host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow.

Amentoflavone inhibits hepatitis B virus infection via the suppression of preS1 binding to host cells.

Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapeutic drugs for chronic HBV infection use IFN and nucleos(t)ide analogs; however, their efficacy is limited. Thus, there is an urgent need to develop new antivirals for HBV therapy. In this study, we identified a plant-derived polyphenolic bioflavonoid, amentoflavone, as a new anti-HBV compound. Amentoflavone treatment dose-dependently inhibited HBV infection in HBV-susceptible cells with HepG2-hNTCP-C4 and primary human hepatocyte PXB-cells. A mode-of-action study showed that amentoflavone inhibits the viral entry step, but not the viral internalization and early replication processes. Attachment of HBV particles as well as HBV preS1 peptide to HepG2-hNTCP-C4 cells was inhibited by amentoflavone. The transporter assay revealed that amentoflavone partly inhibits uptake of sodium taurocholate cotransporting polypeptide (NTCP)-mediated bile acid. Furthermore, effect of various amentoflavone analogs on HBs and HBe production from HBV-infected HepG2-hNTCP-C4 cells was examined. Robustaflavone exhibited comparable anti-HBV activity to that of amentoflavone and an amentoflavone-7,4', 4‴-trimethyl ether derivative (sciadopitysin) with moderate anti-HBV activity. Cupressuflavone or the monomeric flavonoid apigenin did not exhibit the antiviral activity. Amentoflavone and its structurally related biflavonoids may provide a potential drug scaffold in the design of a new anti-HBV drug inhibitor targeting NTCP.

Hepatitis B Virus A1762T/G1764A Mutation Has a Minor Effect on the Viral Spliced DNA Expression

Background: Hepatitis B virus (HBV) is the major cause of chronic hepatitis B, which can lead to liver cirrhosis and hepatocellular carcinoma. During HBV replication, splicing of viral RNA frequently occurs, and the spliced RNA or DNA has been reported to be related to the development of liver disease. HBV transcription is mainly regulated by core promoter ranging from nucleotide 1613 to 1849 and the A1762T/G1764A mutation, which can increase the viral transcription, is frequently detected in this region. Objective: The study aimed to analyze the effect of the A1762T/G1764A mutation in the core promoter of HBV on viral RNA splicing. Methods: The wild type (WT) and the A1762T/G1764A mutant HBV genome were cloned into the pCDNA3.1 vector, which was then transiently transfected into HepG2 cells. The intracellular HBV DNA and core protein were determined by the Southern blot and the Western blot, respectively. The relative level of HBSD was examined by quantitative PCR using TB green reagent. Results: the A1762T/G1764A mutation could enhance the ability of viral replication, however, had a minor effect on HBSD expression. Conclusion: The double mutation in CP could regulate the viral transcription, but was not involved in the viral RNA splicing.

Serum retinol-binding protein 4 as a predictor of fibrosis regression and response to direct-acting antiviral drugs in chronic hepatitis C virus patients

BackgroundHepatitis C virus is the underlying cause of chronic hepatitis which frequently progresses to cirrhosis and hepatocellular carcinoma. In addition, HCV is thought to cause steatosis, dyslipidemia, insulin resistance, diabetes, obesity, and cardiovascular events. The aim of this study is to evaluate the role of serum RBP-4 in the prediction of fibrosis regression and the response of treatment among chronic HCV patients receiving direct-acting antiviral agents.MethodsThis study included 40 chronic HCV Egyptian patients, divided into two groups: Naive cases, 20 chronic HCV patients before starting first line of treatment; Relapser cases, 20 chronic HCV patients who were non-responders before starting second line treatment; and 10 healthy subjects as control. Laboratory investigations including complete blood count, full hepatic profile, fibroscan assessment, and retinol-binding protein-4 level at baseline and re-assessed 12 weeks after the end of treatment [sustained virological response SVR12]. Student T test, analysis of variance, chi-square, Tukey’s test, and Pearson correlation coefficient tests were used for statistical analysis.ResultsBaseline retinol-binding protein-4 level was significantly higher in the naïve case group than in the relapser and control groups with a P value of P value of < 0.001. All the naïve patients had 100% SVR12, only 90% of the relapser group achieved SVR12. A significant reduction in retinol-binding protein-4 and fibrosis staging and measurements by fibroscan among all studied patients were noted after receiving direct acting antivirals (P value < 0.001). Retinol-binding protein-4 levels before and after treatment were significantly lower among F4 patients in comparison to those of F1–F3 patients (P value 0.002, 0.009, respectively). The best cutoff value of retinol-binding protein-4 in the prediction of liver cirrhosis (F4) was ≤ 46 pg/ml with sensitivity of 100% and specificity of 66.67%.ConclusionSerum retinol-binding protein-4 was found to be higher in chronic HCV infection with a significant reduction after successful eradication. Its level is much lower in cirrhotic patients [F4]. As a result, retinol-binding protein-4 may have a promising role in assessing direct acting antivirals response, as well as a prognostic value in predicting liver cirrhosis.

Hepatitis in India: challenges, efforts, and recommendations

Hepatitis in India: challenges, efforts, and recommendations

A Case of Hepatitis E in The Liver Transplant Recipient

Hepatitis E Virus (HEV) is an underrecognized cause of chronic hepatitis in the solid organ transplant (SOT) population. Amongst the liver transplant population, HEV viremia may persist and can cause advanced fibrosis and cirrhosis. A high index of suspicion is necessary for diagnosis. This is a case of a 63-year-old liver transplant recipient who presented with abnormal liver tests and ultimately diagnosed with chronic Hepatitis E. He was treated with Ribavirin with subsequent normalization of his liver tests.

Hepatitis B-Virus Genotype D is Prevalent in a Multi-Ethnic Population of Karachi, Pakistan

The Hepatitis B virus (HBV) remains a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) globally. HBV is broadly classified into ten genotypes (A-J). Each genotype is distinctive due to its geographical distribution, response to certain treatments, and association with disease severity. The investigation of HBV genotypes is worthwhile as it will help predict patient prognosis and ensure effective treatment. Therefore, this study aimed to determine the prevalent HBV genotypes in the multiethnic population of Karachi, Pakistan. A total of 206 patients were enrolled in the study from January 2011 to April 2016. Of the 206 patients that we investigated, a total of 159 patients were positive for HBV infection. Furthermore, genotyping analysis of the positive samples revealed that the most common genotypes were HBV D (59% samples (n=94)), co-infection with genotype A &amp; D (22% (n=35)) and genotype A (16% (n=26)). Most of the HBV-positive patients were males between 21 to 40 years of age. As genotype D is associated with worse outcomes, it is imperative that HBV awareness programs are launched to prevent the further spread of infections in this densely populated city.

Discovery of a first-in-class orally available HBV cccDNA inhibitor

The persistence of covalently closed circular DNA (cccDNA) in infected hepatocytes is the major barrier preventing viral eradication with existing therapies in patients with chronic hepatitis B. Therapeutic agents that can eliminate cccDNA are urgently needed to achieve viral eradication and thus HBV cure. A phenotypic assay with HBV-infected primary human hepatocytes (PHHs) was employed to screen for novel cccDNA inhibitors. A HBVcircle mouse model and a uPA-SCID (urokinase-type plasminogen activator-severe combined immunodeficiency) humanized liver mouse model were used to evaluate the anti-HBV efficacy of the discovered cccDNA inhibitors. Potent and dose-dependent reductions in extracellular HBV DNA, HBsAg, and HBeAg levels were achieved upon the initiation of ccc_R08 treatment two days after the HBV infection of PHHs. More importantly, the level of cccDNA was specifically reduced by ccc_R08, while it did not obviously affect mitochondrial DNA. Additionally, ccc_R08 showed no significant cytotoxicity in PHHs or in multiple proliferating cell lines. The twice daily oral administration of ccc_R08 to HBVcircle model mice, which contained surrogate cccDNA molecules, significantly decreased the serum levels of HBV DNA and antigens, and these effects were sustained during the off-treatment follow-up period. Moreover, at the end of follow-up, the levels of surrogate cccDNA molecules in the livers of ccc_R08-treated HBVcircle mice were reduced to below the lower limit of quantification. We have discovered a small-molecule cccDNA inhibitor that reduces HBV cccDNA levels. cccDNA inhibitors potentially represent a new approach to completely cure patients chronically infected with HBV. Covalently closed circular DNA (cccDNA) persistence in HBV-infected hepatocytes is the root cause of chronic hepatitis B. We discovered a novel small-molecule cccDNA inhibitor that can specifically reduce cccDNA levels in HBV-infected hepatocytes. This type of molecule could offer a new approach to completely cure patients chronically infected with HBV.

Long-term liver allograft fibrosis: A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection.

Liver transplantation (LT) is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease. With improvements in organ preservation techniques, perioperative care, and immunosuppression, there is better patient and graft survival following LT, and assessment of the liver allograft in long-term survivors is becoming increasingly important. Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults. However, no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients, as they have been transplanted for non-recurrent liver diseases. Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes. Pathological findings are frequently present in liver biopsies obtained after a year post LT. The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters. This narrative review summaries the factors predisposing to long-term liver allograft fibrosis, highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.

First identification of bovine hepacivirus in wild boars

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma in humans. Humans were long considered the only hosts of Hepacivirus. Recently HCV-like sequences have been found in several animal species. Hepaciviruses are considered species-specific but a wider host range and a zoonotic role has been hypothesized. We report the first detection of bovine hepacivirus (BovHepV) sequences in wild boars. A total of 310 wild boars hunted in Campania region were investigated with a pan-hepacivirus nested-PCR protocol for the NS3 gene. Hepacivirus RNA was detected in 5.8% of the animals. Sequence and phylogenetic analysis showed high homology with BovHepV subtype F, with nucleotide identity of 99%. The positive wild boars were georeferenced, revealing high density of livestock farms, with no clear distinction between animal husbandry and hunting areas. These findings might suggest the ability of BovHepV to cross the host-species barrier and infect wild boars.