Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

BACKGROUND: We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). METHODS: A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. RESULTS: A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. CONCLUSIONS: The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

Reduced incidence of hepatitis C in 9 villages in rural Egypt: Progress towards national elimination goals.

BACKGROUND & AIMS: Egypt has a major HCV burden and a well established treatment programme, with an ambitious goal of HCV elimination. Our aim was to assess the impact of a comprehensive HCV prevention, test and treat programme on the incidence of new HCV infections in 9 villages in rural Egypt. METHODS: An HCV "educate, test and treat" project was implemented in 73 villages across 7 governorates in Egypt between 06/2015 and 06/2018. In 2018, in 9 of the villages we re-tested individuals who originally tested HCV antibody (HCV-Ab) and HBsAg negative using rapid diagnostic tests (RDTs); confirmatory HCV RNA testing was performed for positive cases. The incidence rate per 1,000 person-years (py) was calculated, and risk factors for incident HCV infections assessed through an interviewer-administered questionnaire in 1:3 age- and gender-matched cases and controls. RESULTS: Out of 20,490 individuals who originally tested HCV-Ab negative in the 9 villages during the 2015-2016 implementation of the "educate, test and treat" programme, 19,816 (96.7%) were re-tested in 2018. Over a median of 2.4 years (IQR 2.1-2.7), there were 19 new HCV infections all of which were HCV RNA positive (incidence rate 0.37/1,000 py) (95% CI 0.24-0.59). Compared to a previous estimate of incidence in the Nile Delta region (2.4/1,000 py) from 2006, there was a substantial reduction in overall incidence of new HCV infections. Exposures through surgery (odds ratio 51; 95% CI 3.5-740.1) and dental procedures (odds ratio 23.8; 95% CI 2.9-194.9) were significant independent predictors of incident infections. CONCLUSIONS: This is the first study to show a substantial reduction in incidence of new HCV infections in a sample of the general population in Egypt following attainment of high testing and treatment coverage. New infections were significantly associated with healthcare-associated exposures. LAY SUMMARY: Egypt has a major national HCV testing and treatment programme with the goal of eliminating HCV infection. We assessed the impact of a comprehensive HCV prevention, test and treat programme in 73 villages that achieved high coverage of testing and treatment on the subsequent incidence of new HCV infections in nine of the villages. We re-tested people who were previously HCV antibody negative and found that the rate of new HCV infections was greatly reduced compared to previous estimates. We also found that exposure through surgery and dental procedures were associated with these new infections. This highlights the importance of continued strengthening of infection control and prevention measures, alongside treatment scale-up.

Fibrogenic/Angiogenic Linker for Non-Invasive Assessment of Hepatic Fibrosis Staging in Chronic Hepatitis C Among Egyptian Patients.

Background and rationale for the study. Liver biopsy is the golden standard for staging liver fibrosis, but it may be accompanied by complications. Because of this complication, the aim of this study is to evaluate a simple noninvasive score to assess hepatic fibrosis in chronic hepatitis C genotype 4 patients which is very may have an important in diagnosis and therapeutic decision. This score [HA vascular (HAV) score] is a combination of direct markers [hyaluronic acid (HA) and vascular endothelial growth factor (VEGF)] and indirect markers [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)]. RESULTS: Samples were collected from 220 patients (F0-F4): an estimated group (n = 120) and a validated group (n = 100). HA and VEGF levels, HCV RNA, liver function tests, platelet counts were assayed, Fibroscan was done and liver biopsy was taken and the stage of liver fibrosis and the grade of inflammatory activity was calculated according to Metavir score system. HA vascular (HAV) score = -35.1 + 0.14 (HA) (ng/L) + 0.03 (VEGF) (pg/mL) + (-6.7) [AAR (AST/ALT ratio)]. The HAV score produced areas under curve of 0.979 and 0.994 for significant (F2-F4) and advanced fibrosis (F3-F4) (cut off = 0.583 and 6.3, respectively). Surprisingly, the validation study of this score gave very good values of AUCs i.e. 0.990, 0.996 and 0.995 for significant, advanced and liver cirrhosis. CONCLUSIONS: Our developed score can not only help to assess liver fibrosis staging effectively but also avoid the invasiveness and the limitations of liver biopsy in Egyptian hepatitis C virus patients.

Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update.

Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end result of any injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Despite the fact that liver biopsy (LB) has been considered the "gold standard" of assessment of hepatic fibrosis, LB is not favored by patients or physicians owing to its invasiveness, limitations, sampling errors, etc. Therefore, many alternative approaches to assess liver fibrosis are gaining more popularity and have assumed great importance, and many data on such approaches are being generated. The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The first consensus guidelines of the APASL recommendations on hepatic fibrosis were published in 2009. Due to advances in the field, we present herein the APASL 2016 updated version on invasive and non-invasive assessment of hepatic fibrosis. The process for the development of these consensus guidelines involved review of all available published literature by a core group of experts who subsequently proposed consensus statements followed by discussion of the contentious issues and unanimous approval of the consensus statements. The Oxford System of the evidence-based approach was adopted for developing the consensus statements using the level of evidence from one (highest) to five (lowest) and grade of recommendation from A (strongest) to D (weakest). The topics covered in the guidelines include invasive methods (LB and hepatic venous pressure gradient measurements), blood tests, conventional radiological methods, elastography techniques and cost-effectiveness of hepatic fibrosis assessment methods, in addition to fibrosis assessment in special and rare situations.

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.

Non-invasive assessment of portal hypertension and liver fibrosis using contrast-enhanced ultrasonography.

Portal hypertension and hepatic fibrosis are key pathophysiologies with major manifestations in cirrhosis. Although the degree of portal pressure and hepatic fibrosis are pivotal parameters, both are determined using invasive procedures. Ultrasound (US) is a simple and non-invasive technique that is available for use worldwide in the abdominal field. Because of its safety and easy of use, contrast-enhanced US is one of the most frequently used tools in the management of liver tumors for the detection and characterization of lesions, assessment of malignancy grade, and evaluation of therapeutic effects. This wide range of applications drives the practical use of contrast-enhanced US for evaluation of the severity of portal hypertension and hepatic fibrosis. The present article reviews the recent progress in contrast-enhanced US for the assessment of portal hypertension and hepatic fibrosis.

Role of hyaluronic acid, its degrading enzymes, degradation products, and ferritin in the assessment of fibrosis stage in Egyptian patients with chronic hepatitis C.

BACKGROUND/AIMS: Liver biopsy is considered a gold standard for fibrosis staging, but it has a high risk of morbidity. Therefore, there is an interest in developing noninvasive markers for the prediction of liver fibrosis stages. METHODS: Hyaluronic acid, ferritin, N-acetyl-ß-D-glucosaminidase, ß-glucuronidase, glucosamine, aspartate transaminase, and alanine transaminase were assayed in 210 individuals with chronic hepatitis C infection. Statistical analysis was carried out by logistic regression and receiver-operating characteristic curves. RESULTS: The best linear combination of only significant blood markers was used for the determination of the fibrosis discriminant score; score=[1.64 (numerical constant)-0.002×hyaluronic acid (pg/l)-2.68×ß-glucuronidase (µmol/ml/min)-0.026×glucosamine (µg/dl)-0.001×ferritin-0.033 (ng/ml)×aspartate transaminase/alanine transaminase]. The selected fibrosis discriminant score function correctly classified 81% of patients with severe liver fibrosis at a discriminant cut-off score=0.55 (i.e. less than 0.55 indicated mild liver fibrosis and greater than 0.55 indicated severe liver fibrosis), with a sensitivity of 100% and a specificity of 73%. CONCLUSION: A simple fibrosis index can be useful to select hepatitis C virus-infected patients with a very low risk of significant fibrosis in whom the protocol of liver biopsies may be avoided.

Evaluation of liver stiffness measurement by fibroscan as compared to liver biopsy for assessment of hepatic fibrosis in children with chronic hepatitis C.

The study evaluated liver stiffness measurement (LSM) using non-invasive transient elastography (TE) in comparison with liver biopsy for assessment of hepatic fibrosis in children with chronic hepatitis C (CHC). Thirty children (mean age 10.13 +/- 3.4 years) with CHC were subjected to histopathological assessment of liver biopsy specimens using METAVIER score and LSM using TE (FibroScan) as well as appropriate laboratory investigations. The results showed a highly significant stepwise increase of the mean liver stiffness values with increasing histological severity of hepatic fibrosis with the highest level detected in patients with stage F4 "cirrhosis" and significant differences for F3 and F4 vs. other fibrosis stages. There were significant positive correlations between LSM and several parameters of activity and progression of the chronic liver disease including METAVIER fibrosis stages (r=0.774, p=0.0001), necroinflammatory activity grades, AST, ALT, total serum bilirubin, prothrombin time and Child-Pugh grades as well as biochemical serum fibrosis markers (Fibrotest, Actitest, AST-to-platelet ratio index, Forns index and hyaluronic acid). The variables significantly negatively associated with the LSM were platelets count and serum albumin. The highest predictive performance of LSM was detected for stage F4 "cirrhosis", followed by F3 "advanced fibrosis" where accuracy of(96.7%, 85.3%) and AUROC of (1.00, 0.815) were obtained for these fibrosis stages at cutoff values of 9.5 and 12.5 kPa, respectively. The negative predictive values to exclude advanced fibrosis and cirrhosis at these cutoffs were high, whereas positive predictive values were modest.

Current status and future directions in the management of chronic hepatitis C.

Hepatitis C virus (HCV) is endemic worldwide, and it causes cirrhosis and other complications that often lead to death; nevertheless, our knowledge of the disease and its mechanisms is limited. HCV is most common in underdeveloped nations, including many in Africa and Asia. The virus is usually transmitted by parenteral routes, but sexual, perinatal, and other types of transfer have been known to occur. Approximately 80% of individuals who contract hepatitis C develop a chronic infection, and very few are able to spontaneously clear the virus. Because hepatitis C is asymptomatic in the majority of patients, the presence of HCV RNA in the serum is the best diagnostic tool. Although serious complications from hepatitis C may not occur for 20 years, 1/5 of chronic patients eventually develop life - threatening cirrhosis. More research is needed on the different therapy options for the disease, and many factors, most importantly the genotype of the virus, must be taken into account before beginning any treatment. As there is no vaccine against HCV at present, the most effective and recommended therapy is pegylated-interferon-α-2a plus ribavirin. While interferon is marginally effective as a monotherapy, both adding the moiety and combining it with ribavirin have been shown to dramatically increase its potency. While there are numerous alternative and complementary medicines available for patients with hepatitis C, their efficacy is questionable. Currently, research is being done to investigate other possible treatments for hepatitis C, and progress is being made to develop a vaccine against HCV, despite the many challenges the virus presents. Until such a vaccination is available, prevention and control methods are important in containing and impeding the spread of the virus and mitigating its deleterious effects on the health of people and communities worldwide.

Regression of fibrosis in paediatric autoimmune hepatitis: morphometric assessment of fibrosis versus semiquantiatative methods.

BACKGROUND: Regression of hepatic fibrosis in patients with autoimmune hepatitis (AIH) has been described in response to immunosuppressive therapy. These studies, however, besides being few in number, were conducted on adult populations. Our aim was to assess the regression of hepatic fibrosis, using morphometric assessment of fibrosis versus semi-quantitative methods, in children with AIH who achieved clinical and biochemical remission. Thirteen patients who achieved clinical and biochemical remission were included in the study, out of 62 children with AIH. Repeat biopsy was performed after 6 to 12 months of clinical and biochemical remission. Morphometric assessment of fibrosis was performed and correlated with METAVIR and Ishak semi-quantitative scores. RESULTS: The study group included eight male and five female patients. The median age at presentation was 4 years (range 2 to 12 years). The mean duration of treatment was 22 +/- 7.3 months, and the mean interval between biopsies was 26.2 +/- 6.5 months. Following therapy, there was significant reduction in aspartate aminotransferase, ALT and IgG levels as well as improvement of necroinflammation. The mean fibrosis scores were significantly decreased from 4.5 +/- 1.19 and 2.9 +/- 0.7 before therapy to 2.7 +/- 1.16 and 2 +/- 0.8 after treatment as assessed by Ishak and METAVIR scores, respectively (P = 0.001 and 0.004). The mean morphometric assessment of fibrosis before treatment was 20% +/- 9.7 and following therapy it decreased to 5.6% +/- 3.9 (P = 0.000). CONCLUSION: Significant regression of fibrosis in paediatric AIH could occur with current therapeutic regimens. Morphometric assessment of fibrosis is more sensitive than semi-quantitative methods to identify changes in fibrosis.

Does schistosomiasis interfere with application of the Knodell score for assessment of chronic hepatitis C?

BACKGROUND: Schistosoma mansoni (SM) is a significant cause of liver disease in many countries. Chronic hepatitis C (HCV) is a worldwide health problem. The association of SM and chronic HCV is not uncommon, especially in areas where both diseases occur. The possible synergistic relationship between them is controversial. Also, the degree of necroinflammatory injury and the stage of fibrosis in patients with mixed schistosomiasis and chronic HCV remains unclear. MATERIAL/METHODS: 185 individuals were studied: 25 with pure SM, 100 with pure HCV, and 60 mixed HCV and SM (HCV+S), selected from 222 biopsied patients with chronic liver disease treated at the liver unit of the Internal Medicine Department, Mansoura University (July 1999-May 2000). They were subjected to rectal snip and serological test for schistosomiasis, liver functions, HBV, HCV serological markers, serum qualitative PCR, and liver biopsy. Masson trichrome stain was performed to assess fibrosis. Immunohistochemical staining was performed for HBsAg and HBcAg. The Modified Knodell score was applied to assess the biopsy. RESULTS: Five of the 25 pure SM and 2 of the HCV+S group revealed schistosomal granuloma. 30% of the pure HCV and 33% of the HCV+S patients were found to be cirrhotic. No statistically significant difference was identified between the groups as regards necroinflammatory injury or Knodell score, or the stage of fibrosis. CONCLUSIONS: Schistosomal hepatic infection does not lead to more severe or progressive disease in patients with chronic hepatitis C.