COVID-19 and liver disease: An update. / Actualización en COVID-19 y enfermedad hepática.

The SARS-CoV-2 pandemic has proven to be a serious challenge for the Spanish healthcare system. The impact of the virus on the liver is not well known, but in patients with chronic liver disease, mostly in advanced stages, it can critically compromise survival and trigger decompensation. Treatment in this subpopulation is complex due to the potential hepatotoxicity of some of the medicinal products used. Moreover, the pandemic has also negatively impacted patients with liver disease who have not contracted COVID-19, since the reallocation of human and material resources to the care of patients with the virus has resulted in a decrease in the treatment, diagnosis and follow-up of patients with liver disease, which will surely have negative consequences in the near future. Efficient reorganization of hepatology units is a priority to minimise the impact of the pandemic on a population as vulnerable as liver disease patients.

Assessment of hepatitis E virus (HEV) in the edible goat products pointed out a risk for human infection in Upper Egypt.

Hepatitis E virus (HEV) infection is endemic in developed and developing countries. Although the seroprevalence of HEV among the Egyptians is high, the sources of HEV infection in Egypt are not completely identified. Zoonotic HEV transmission among Egyptians is underestimated. Recently, we detected HEV in the milk of cows, this suggests the possibility of HEV transmission through the ingestion of contaminated milk. However, the role of small ruminants especially the goats in HEV epidemiology in Egypt remains unclear. Herein, we screened HEV markers in the edible goat products, mainly the milk and liver and we assessed the risk factor for HEV infection to the goat owners. A total of 280 goat milk samples were collected from 15 villages in the Assiut governorate. Anti-HEV IgG and HEV Ag were detected in 7.14% and 1.8% of the samples, respectively. HEV RNA was detected in 2 milk samples, cladogram analysis revealed that the isolated viruses belonged to HEV-3 subtype 3a. One viral isolate showed high homology to HEV recently isolated from the cow milk in the same geographic area. The level of anti-HEV IgG and HEV Ag were comparable in the milk and matched blood samples. While the urine and stool of HEV seropositive goats tested negative for HEV markers. HEV RNA was also detectable in the fresh goat liver samples (n = 2) derived from HEV seropositive goats. Finally, we analyzed HEV seroprevalence in households (n = 5) that owned the seropositive goats and households (n = 5) that owned the seronegative goats. Interestingly, anti-HEV IgG was recorded in 80% of households owned and frequently consumed the products of HEV seropositive goats, while HEV markers were not detectable in the owners of the seronegative goats. In conclusion: Here, we report HEV in the milk and liver of goats distributed in the villages of Assiut governorate. Higher HEV seroprevalence was recorded in the households that owned the seropositive goats. Investigation of the goat products is pivotal to assess the risk factor of HEV transmission to villagers in the Assiut governorate.

Noninvasive assessment of liver fibrosis in chronic hepatitis C virus patients compared to liver biopsy: the experience of tertiary level hospital in Serbia.

BACKGROUND: Chronic hepatitis C virus (HCV) infection, that is defined by active carriage of HCV RNA in the blood, is represents one of the major public health problems worldwide. In Serbia, the prevalence of anti-HCV positive persons in the general population, is estimated on average 1.13%. METHODS: The aim of our study was to evaluate the ability of noninvasive scores in order to define the degree of liver fibrosis, and to assess the effect of host and viral factors on fibrosis in chronic HCV patients. In a retrospective analysis a total of 814 patients with chronic HCV infection were included. Liver fibrosis scores were calculated, and in particular AST/ALT Score APRI, Forns Index, and FIB-4 score, and all of them compared with histological classification. RESULTS: We found that noninvasive biochemical scores of fibrosis, have a good performance especially to distinguish mild and moderate fibrosis to advanced fibrosis. In particular, we found that FIB-4 score is a useful screening tool to accurately exclude patients with advanced disease. CONCLUSIONS: Noninvasive liver fibrosis scores are efficient tools in the management and follow-up of HCV patients in clinical practice.

Liver safety assessment in clinical trials of new agents for chronic hepatitis B.

Investigational agents that reduce or eliminate covalently closed circular DNA (cccDNA) or enhance host immunity against hepatitis B virus (HBV)-infected hepatocytes are intended to induce a durable off-treatment clearance of hepatitis B surface antigen (HBsAg) (referred to as functional cure). The aim of this paper was to highlight challenges in interpreting liver safety data in clinical trials of these agents when given alone or in combination regimens. The incidence, grading and management of spontaneous serum ALT flares in untreated chronic HBV patients are reviewed along with a summary of serum ALT flares observed during the registration trials for peginterferon and nucleos(t)ide reverse transcriptase inhibitors. Recommendations regarding the detection, management and interpretation of liver safety biomarker data in future clinical trials as well as suggested inclusion and exclusion criteria for phase 1/2 vs phase 3 studies are provided. Criteria to help classify liver safety signals as being due to the intended therapeutic response, emergence of drug-resistant HBV virions, or idiosyncratic drug-induced liver injury are provided along with a review of the role of an expert hepatic adjudication panel in assessing a compound's hepatotoxicity profile. Finally, an algorithmic approach to the differential diagnosis and recommended medical evaluation and management of individual clinical trial patients that develop a liver safety signal is provided along with the rationale to collect and test research blood samples for future mechanistic studies.

Temporal Changes and Regional Variation in Acceptance of Hepatitis C Virus-Viremic Livers.

The high efficacy of current hepatitis C virus (HCV) therapy and increased numbers of HCV-infected deceased donors have changed the paradigm of HCV in liver transplantation (LT). Modeling studies have been performed to evaluate the optimal timing of HCV treatment (before versus after LT) in HCV-infected patients and to assess the cost-effectiveness of transplanting HCV-infected livers into HCV- patients. However, these models rely on historical data and have not quantified the temporal changes in the median Model for End-Stage Liver Disease (MELD) score at transplant of recipients of an HCV-infected liver across geographic areas. We performed a retrospective cohort study of Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data of nonstatus 1 deceased donor LT recipients from January 1, 2016, to December 31, 2018, and we calculated the difference in allocation MELD score in recipients of HCV nucleic acid test (NAT)- versus NAT+ livers by year and UNOS region. We used Pearson correlation coefficients to assess the relationship between MELD score difference in recipients of HCV NAT+ versus HCV NAT- livers and the proportion of non-HCV recipients of HCV NAT+ livers. Nationally, the allocation MELD score difference at LT in recipients of HCV NAT+ versus NAT- livers did not change (4-point difference). This stability was seen in regions 3, 5, and 10. In regions 1, 7, 8, 9, and 11, the MELD score difference decreased, which is a diminishing advantage. However, in regions 2 and 4, it increased, which is a rising advantage. In 2018, recipients of HCV NAT+ livers had a lower MELD score in 9/11 regions, and the MELD score advantage of accepting HCV NAT+ livers had a moderate inverse correlation with the regional use in non-HCV patients (r = -0.53). These data should be used to inform clinicians of the pre- and post-LT trade-offs of HCV treatment.

The inpatient hospital burden of comorbidities in HCV-infected patients: A population-based study in two Italian regions with high HCV endemicity (The BaCH study).

BACKGROUND & AIMS: Hepatitis C (HCV) is associated with several extrahepatic manifestations, and estimates of the hospitalization burden related to these comorbidities are still limited. The aim of this study is to quantify the hospitalization risk associated with comorbidities in an Italian cohort of HCV-infected patients and to assess which of these comorbidities are associated with high hospitalization resource utilization. METHODS: Individuals aged 18 years and older with HCV-infection were identified in the Abruzzo's and Campania's hospital discharge abstracts during 2011-2014 with 1-year follow-up. Cardio-and cerebrovascular disease, diabetes and renal disease were grouped as HCV-related comorbidities. Negative binomial models were used to compare the hospitalization risk in patients with and without each comorbidity. Logistic regression model was used to identify the characteristics of being in the top 20% of patients with the highest hospitalization costs (high-cost patients). RESULTS: 15,985 patients were included; 19.9% had a liver complication and 48.6% had one or more HCV-related comorbidities. During follow-up, 36.0% of patients underwent at least one hospitalization. Liver complications and the presence of two or more HCV-related comorbidities were the major predictors of hospitalization and highest inpatient costs. Among those, patients with cardiovascular disease had the highest risk of hospitalization (Incidence Rate Ratios = 1.42;95%CI:1.33-1.51) and the highest likelihood of becoming high-cost patients (Odd Ratio = 1.37;95%CI:1.20-1.57). CONCLUSION: Beyond advanced liver disease, HCV-related comorbidities (especially cardiovascular disease) are the strongest predictors of high hospitalization rates and costs. Our findings highlight the potential benefit that early identification and treatment of HCV might have on the reduction of hospitalization costs driven by extrahepatic conditions.

National landscape of HIV+ to HIV+ kidney and liver transplantation in the United States.

The HIV Organ Policy Equity (HOPE) Act, enacted on November 21, 2013, enables research on the transplantation of organs from donors infected with human immunodeficiency virus (HIV) (HIV+) into HIV+ individuals who, prior to transplantation, are infected with HIV. In 2015, the Organ Procurement and Transplantation Network revised organ allocation policies on November 21, and on November 23, the Secretary of Health and Human Services published research criteria and revised the Final Rule accordingly. The HOPE Act appears to be underutilized to date. As of December 31, 2018, there were 56 donors recovered (50 donors transplanted) resulting in 102 organs transplanted (31 liver, 71 kidney). As of December 31, 2018, 212 registrations were indicated on the waiting list as willing to accept an HIV+ kidney or liver, most of which were waiting in active status. Due to the limited number of transplants performed to date, definitive safety conclusions cannot be reached at this time, though current data suggest that 1-year patient and graft survival does not deviate in a major way from that observed in HIV+ recipients of non-HIV+ organs or non-HIV+ recipients. As safety data are reviewed and disseminated, it is anticipated that HOPE participation will increase should safety signals remain low.

A panel of a mitogenic (PDGF), biochemical (albumin) and demographic (age) parameters for the non-invasive assessment of hepatic fibrosis.

Background: Several studies have investigated certain fibrosis markers that incorporate liver function tests, fragments of liver-matrix components and/or degraded products generated by hepatic stellate cells for determining the degree of hepatic fibrosis. However, the role of these molecules in the development of hepatic fibrosis is unclear. This work aimed (a) to determine whether platelet-derived growth factor (PDGF) is linked to different stages of hepatic fibrosis and (b) investigate its diagnostic performance alongside other laboratory and demographic factors in assessing liver fibrosis in chronic hepatitis C infection. Methods: Liver-fibrosis was staged according to Fibroscan, PDGF quantified using ELISA, and liver function tests and other analytes determined by standard techniques in 239 patients with chronic hepatitis C virus infection. Results: Patients with significant (F2-F4), advanced fibrosis (F3-F4) and cirrhotic liver disease (F4) showed significantly (P<0.0001) higher PDGF levels increase respectively compared to stage F0/1. We used this to construct the PARA-Index (PDGF/albumin ratio, age), which performed well in assessing hepatic-fibrosis stages with AUCs of 0.91, 0.87 and 0.86 for identifying F2-F4, F3-F4 and F4, respectively. Additionally, the PARA-Index correlated strongly (r=0.65, P<0.0001) with the severity of the fibrosis. An elevated PARA-index provided odds ratios of 21.0, 20.7 and 10.3 for developing F2-F4, F3-F4 and F4, respectively. Conclusion: A panel of mitogenic (PDGF), biochemical (albumin) and demographical (age) parameters may improve liver-fibrosis staging with a high degree of accuracy in those with a hepatitis C virus infection.

Epidemiology and Elimination of HCV-Related Liver Disease.

Hepatitis C virus (HCV) infection, defined by active carriage of HCV RNA, affects nearly 1.0% of the worldwide population. The main risk factors include unsafe injection drug use and iatrogenic infections. Chronic HCV infection can promote liver damage, cirrhosis and hepatocellular carcinoma (HCC) in affected individuals. The advent of new second-generation, direct-acting antiviral (DAA) agents allow a virological cure in more than 90% of treated patients, and therefore prevent HCV-related complications. Recently, concerns have been raised regarding the safety of DAA-regimens in cirrhotic patients with respect to the occurrence and the recurrence of HCC. Here, we review the current available data on HCV epidemiology, the beneficial effects of therapy, and discuss the recent controversy with respect to the potential link with liver cancer. We also highlight the challenges that have to be overcome to achieve the ambitious World Health Organization objective of HCV eradication by 2030.

Economic and clinical burden of viral hepatitis in California: A population-based study with longitudinal analysis.

BACKGROUND: Economic burden of HBV and HCV infection are trending upwards. AIMS: Compare hepatitis B virus (HBV) and hepatitis C virus (HCV) related hospital admission rates, charges, mortality rates, causes of death in a US population-based study. METHODS: Retrospective cohort analysis of HBV and HCV patients from the California Office of Statewide Health Planning and Development (2006-2013) database. RESULTS: A total of 23,891 HBV and 148,229 HCV patients were identified. Across the 8-year period, the mean increase for all-cause ($1,863 vs $1,388) and liver-related hospitalization charges ($1,175 vs $675) were significantly higher for the HBV cohort compared to the HCV cohort. HBV patients had significantly higher liver-related hospital charges per person per year than HCV patients after controlling for covariates ($123,239 vs $111,837; p = 0.002). Compared to HCV patients, adjusted mortality hazard ratio was slightly lower in HBV patients (relative risk = 0.96; 95% CI 0.94-0.99). The major causes and places of death were different. The three major causes of death for HBV were: other malignant neoplasms (35%), cardiovascular disease/other circulatory disorders (17%), and liver-related disease (15%) whereas for HCV patients were: liver-related disease (22%), other malignant neoplasms (20%), and cardiovascular disease (16%). Regarding the place of death, 53% of HBV patients and 44% of HCV patients died in hospital inpatient, respectively. CONCLUSIONS: HBV patients incurred higher liver-related hospital charges and higher mean increase for all-cause and liver-related hospitalization charges over the 8-year period compared to HCV patients. HBV patients had slightly lower mortality rate and their major causes and places of death were noticeably different from HCV patients.

Epidemiology, determinants, and management of AIDS cholangiopathy: A review.

Diseases of the liver and biliary tree have been described with significant frequency among patients with human immunodeficiency virus (HIV), and its advanced state, acquired immunodeficiency syndrome (AIDS). Through a variety of mechanisms, HIV/AIDS has been shown to affect the hepatic parenchyma and biliary tree, leading to liver inflammation and biliary strictures. One of the potential hepatobiliary complications of this viral infection is AIDS cholangiopathy, a syndrome of biliary obstruction and liver damage due to infection-related strictures of the biliary tract. AIDS cholangiopathy is highly associated with opportunistic infections and advanced immunosuppression in AIDS patients, and due to the increased availability of highly active antiretroviral therapy, is now primarily seen in instances of poor access to anti-retroviral therapy and medication non-compliance. While current published literature describes well the clinical, biochemical, and endoscopic management of AIDS-related cholangiopathy, information on its epidemiology, natural history, and pathology are not as well defined. The objective of this review is to summarize the available literature on AIDS cholangiopathy, emphasizing its epidemiology, course of disease, and determinants, while also revealing an updated approach for its evaluation and management.

Assessment of liver fibrosis with acoustic radiation force impulse imaging versus liver histology in patients with chronic hepatitis C: a pilot study.

BACKGROUND: Acoustic radiation force impulse imaging (ARFI) involves the mechanical excitation of tissues using short-duration acoustic pulses to generate localized displacements in tissue. The displacements results in shear-wave propagation, tracked by ultrasonography (US) correlation-based methods and recorded in meters per seconds. AIM: To compare (ARFI) integrated into a conventional US with the standard histological examination of liver biopsy specimens for the assessment of liver fibrosis. MATERIALS AND METHODS: Histological fibrosis staging with standard liver biopsy using the Metavir scoring system as well as fibrosis assessment using ARFI were performed to 80 patients with chronic hepatitis C over a 3-month period. RESULTS: ARFI findings were identical to the biopsy findings in 61 (76.25%) patients.Fifty-eight (67.5%) patients with an early fibrosis stage (F0, F1, and F2) by histology had identical fibrosis stages using ARFI.Only 20 out of 26 patients with an advanced fibrosis stage (F3 and F4) using ARFI had advanced fibrosis histologically. In the advanced fibrosis stages, the sensitivity of ARFI was 70% and specificity was 80%, with positive and negative predictive values of 53.8 and 88.9%, respectively. The accuracy of detection of advanced fibrosis by ARFI was 77.5%. CONCLUSION: ARFI imaging is a promising noninvasive US-based method for the assessment of liver fibrosis.

3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy.

AIM: To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. METHODS: We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. RESULTS: A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). CONCLUSION: Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.

Transient elastography as a noninvasive assessment tool for hepatopathies of different etiology in pediatric type 1 diabetes mellitus.

AIM: To identify the prevalence and effect of hepatopathies of different etiologies among pediatric patients with type 1 diabetes mellitus (T1DM) using transient elastography (TE) and its relation to glycemic control. METHODS: One hundred T1DM patients were studied focusing on liver functions, fasting lipid profile, hemoglobin A1c (HbA1c), hepatitis C virus (HCV), serum immunoglobulins, autoimmune antibodies; anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver kidney microsomal antibody (anti-LKM). Abdominal ultrasound was performed and TE was done for patients with HCV, positive autoimmune antibody and/or abnormal ultrasound findings. RESULTS: Thirty-one patients were found to have one or more hepatic abnormalities; clinical hepatomegaly in 8%, elevated alanine aminotransferase (ALT) in 10%, HCV in 6%, autoimmune hepatitis (AIH) in 11% (10 were positive for ASMA and 2 were positive for ANA while anti-LKM antibodies were negative) and abnormal hepatic ultrasound in 20% (12 non-alcoholic fatty liver disease, 5 AIH, 2 HCV, 1 Mauriac syndrome). Mean liver stiffness in those 31 patients was 7.0±2.1kPa (range, 3.1-11.8kPa); 24 were Metavir F0-F1, 7 were F2-F3 while none was F4. Type 1 diabetic patients with abnormal hepatic ultrasound had higher fasting blood glucose, HbA1c and total cholesterol than those with normal findings. Liver stiffness was significantly higher in patients with abnormal liver ultrasound compared with normal sonography. Liver stiffness was positively correlated to HbA1c and ALT. CONCLUSIONS: Hepatic abnormalities are prevalent in T1DM and related to poor metabolic control. TE provides a non-invasive method for detection of hepatopathy-induced fibrosis.

Assessment of the risk of foodborne transmission and burden of hepatitis E in Switzerland.

The objective of this study was i) to quantify the risk of hepatitis E for Swiss consumers by specified pork products and ii) to estimate the total burden of human food-borne hepatitis E in Switzerland. A quantitative risk assessment from slaughter to consumption was carried out according to the Codex Alimentarius framework. In the hazard characterization, assumptions were made due to the lack of a dose-response relationship for oral exposure to hepatitis E virus (HEV). The prevalence of HEV in 160 pig livers of 40 different Swiss fattening farms was examined and determined to be 1.3% (CI 0.3%; 4.4%). This result was used as input in the risk assessment model, together with data from other published studies. The annual burden of hepatitis E was estimated in terms of Disability Adjusted Life Years (DALY), using data about hepatitis E cases diagnosed between 2010 and 2015 at two major hospitals located in the canton Ticino. Only the risk of foodborne hepatitis E from products containing pork liver was evaluated, as those containing only pork meat could not be evaluated because of lack of data on HEV load in pork. Assuming that successful oral infection occurs in 1% of servings contaminated with high HEV loads (>105 genome copies), and that acute illness develops in 5% of susceptible consumers, the most likely annual number of foodborne hepatitis E cases in Switzerland was estimated to be 1481 (95% CI 552; 4488) if all products containing pork liver were considered. If only high-risk products, such as plain pork liver and liver sausages (e.g. Saucisse au Foie), were considered, the annual number of cases was estimated to be 176 (95% CI 64; 498). We were unable to calculate the total burden of hepatitis E in Switzerland due to lack of data. Yet, for the canton Ticino, it was shown that a significant increase had occurred from <5 DALY per 100,000 inhabitants before 2012 to >50 DALY per 100,000 inhabitants in 2015. This change could partly be due to an increased reporting and higher awareness among medical practitioners. Extrapolation to other regions could be accomplished if detailed information on food consumption patterns were available. Notification of HEV cases and attempts of cases source attribution would improve the basis for risk assessments.

Hepatitis E Virus in Pork and Variety Meats Sold in Fresh Markets.

Swine is an economically important livestock, yet pork consumption and close contact with pigs are associated with the risk of hepatitis E virus (HEV) infection. Limited data on the prevalence of HEV in Southeast Asia have mainly examined farm animals. To investigate the potential zoonotic transmission of HEV from dietary consumption of pork and variety meats (i.e., offal or organ meats), we obtained 1090 liver, 559 pork meat, and 556 intestine samples from fresh markets in the Bangkok metropolitan area between November 2014 and February 2015. The presence of HEV was assessed using reverse-transcription polymerase chain reaction. Concurrently, 720 bile and 553 fecal samples from a slaughterhouse were also examined. Overall, HEV RNA was found in 0.23 % of the market samples and 3.93 % of the slaughterhouse samples. Fecal and bile samples were more likely to test positive compared to liver, pork, and intestine samples (p < 0.001). Phylogenetic analysis showed that all HEV sequences obtained in this study formed a cluster closely related to genotype 3f. Pork and variety meats derived from pigs are commonly sold in fresh markets throughout Southeast Asia. Here, a relatively low HEV prevalence from pork and variety meats sold in Bangkok was found. Additional studies will be required to further assess potential dietary transmission of HEV elsewhere in the region.

Assessment of Domestic Pigs, Wild Boars and Feral Hybrid Pigs as Reservoirs of Hepatitis E Virus in Corsica, France.

In Corsica, extensive pig breeding systems allow frequent interactions between wild boars and domestic pigs, which are suspected to act as reservoirs of several zoonotic diseases including hepatitis E virus (HEV). In this context, 370 sera and 166 liver samples were collected from phenotypically characterized as pure or hybrid wild boars, between 2009 and 2012. In addition, serum and liver from 208 domestic pigs belonging to 30 farms were collected at the abattoir during the end of 2013. Anti-HEV antibodies were detected in 26% (21%-31.6%) of the pure wild boar, 43.5% (31%-56.7%) of hybrid wild boar and 88% (82.6%-91.9%) of the domestic pig sera. In addition, HEV RNA was detected in five wild boars, three hybrid wild boars and two domestic pig livers tested. Our findings provide evidence that both domestic pig and wild boar (pure and hybrid) act as reservoirs of HEV in Corsica, representing an important zoonotic risk for Corsican hunters and farmers but also for the large population of consumers of raw pig liver specialties produced in Corsica. In addition, hybrid wild boars seem to play an important ecological role in the dissemination of HEV between domestic pig and wild boar populations, unnoticed to date, that deserves further investigation.

Diagnostic performance of T lymphocyte subpopulations in assessment of liver fibrosis stages in hepatitis C virus patients: simple noninvasive score.

BACKGROUND/AIMS: Evaluation of liver fibrosis in patients infected with hepatitis C virus is highly useful for the diagnosis of the disease as well as therapeutic decision. Our aim was to develop and validate a simple noninvasive score for liver fibrosis staging in chronic hepatitis C (CHC) patients and compare its performance against three published simple noninvasive indexes. MATERIALS AND METHODS: CHC patients were divided into two groups: an estimated group (n=70) and a validated group (n=52). Liver fibrosis was tested in biopsies using the Metavair score system. CD4 and CD8 count/percentage were assayed by fluorescence-activated cell sorting analysis. RESULTS: The multivariate discriminant analysis selects a function on the basis of absolute values of five biochemical markers: immune fibrosis index (IFI); score=3.07+3.06×CD4/CD8+0.02×α-fetoprotein (U/l)-0.07×alanine aminotransferase ratio-0.005×platelet count (10/l)-1.4×albumin (g/dl). The IFI score produced areas under curve of 0.949, 0.947, and 0.806 for differentiation of all patient categories [significant fibrosis (F2-F4), advanced fibrosis (F3-F4), and cirrhosis (F4)]. CONCLUSION: The IFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage in CHC patients. Our score was more efficient than aspartate aminotransferase to platelet ratio index, fibrosis index, and fibroQ and more suitable for use in Egyptian hepatitis C virus patients.

Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis.

Because polysaccharide and flavone ingredients display good antiviral activity, we developed a flavone/polysaccharide-containing prescription that would be effective against duck viral hepatitis (DVH) and investigated its hepatoprotective effects. Flavones were derived from Hypericum japonicum (HJF) (entire herb of Hypericum japonicum Thunb) and Salvia plebeia (SPF) (entire herb of Salvia plebeia R. Br.), and polysaccharides were derived from Radix Rehmanniae Recens (RRRP) (dried root of Rehmannia glutinosa Libosch). This prescription combination was based on the theory of syndrome differentiation and treatment in traditional Chinese veterinary medicine. In vitro and in vivo experiments were conducted using the three single ingredients compared to the combined HRS prescription to determine their anti-duck hepatitis A viral (anti-DHAV) activity. The results showed that all experimental conditions displayed anti-DHAV activity, but the HRS prescription presented the best effect. To further investigate the hepatoprotective effect of the HRS prescription on DHAV-induced hepatic injury, we tested the mortality rate, the hepatic pathological severity score, plasma biochemical indexes of hepatic function, blood DHAV gene expression levels and peroxidation damage evaluation indexes and then analyzed correlations among these indexes. The results demonstrated that the HRS prescription significantly decreased the mortality rate, reduced the severity of hepatic injury, decreased the hepatic pathological severity score, depressed blood DHAV gene expression levels, and returned the indexes of hepatic function and peroxidation almost to a normal level. These results indicate that the HRS prescription confers an outstanding hepatoprotective effect, and we expect that it will be developed into a new candidate anti-DHAV drug.

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

BACKGROUND AND RATIONALE: The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. MATERIAL AND METHODS: Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. RESULTS: APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.