Progress towards elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission update.

The top 20 highest burdened countries (in disability-adjusted life years) account for more than 75% of the global burden of viral hepatitis. An effective response in these 20 countries is crucial if global elimination targets are to be achieved. In this update of the Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis, we convene national experts from each of the top 20 highest burdened countries to provide an update on progress. Although the global burden of diseases is falling, progress towards elimination varies greatly by country. By use of a hepatitis elimination policy index conceived as part of the 2019 Commission, we measure countries' progress towards elimination. Progress in elimination policy has been made in 14 of 20 countries with the highest burden since 2018, with the most substantial gains observed in Bangladesh, India, Indonesia, Japan, and Russia. Most improvements are attributable to the publication of formalised national action plans for the elimination of viral hepatitis, provision of publicly funded screening programmes, and government subsidisation of antiviral treatments. Key themes that emerged from discussion between national commissioners from the highest burdened countries build on the original recommendations to accelerate the global elimination of viral hepatitis. These themes include the need for simplified models of care, improved access to appropriate diagnostics, financing initiatives, and rapid implementation of lessons from the COVID-19 pandemic.

Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

Multidisciplinary consensus recommendations for management of hepatocellular carcinoma in Middle East and North Africa region.

Hepatocellular carcinoma (HCC) is a growing health concern projected to cross over a million cases worldwide by 2025. HCC presents a significant burden of disease in Middle East and North African (MENA) countries due to a high prevalence of risk factors such as hepatitis C and B infections and rising incidence of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease. In August 2022, an advisory meeting consisting of experts from 5 MENA countries was convened in an attempt to provide consensus recommendations on HCC screening, early diagnosis, current treatment modalities and unmet medical needs in the region. Data were collected from a pre-meeting survey questionnaire and responses analysed and presented during the advisory meeting. This review summarizes the evidence discussed at the meeting and provides expert recommendations on the management of HCC. The 2022 update of Barcelona clinic liver cancer (BCLC) staging and treatment strategy and its implementation in the MENA region was extensively discussed. A key consensus of the expert panel was that multidisciplinary care is crucial to effective patient management that results in better clinical outcomes and overall survival of the patient. The panel recommended the use of predictive and early response biomarkers to guide clinicians in arriving at more effective therapeutic decisions. The experts also emphasized the role of robust screening/surveillance systems, population-based registries, effective referral pathways and standardization of guidelines to ensure the successful management of HCC in the region.

Impacts of the Egyptian national screening and treatment programme for viral hepatitis C: A cost-effectiveness model.

BACKGROUND & AIMS: Egypt used to have one of the highest prevalences of HCV infection worldwide. The Egyptian Ministry of Health launched a national campaign for the detection and management of HCV to reduce its burden. This study aims to carry out a cost-effectiveness analysis to evaluate the costs and benefits of the Egyptian national screening and treatment programme. METHODS: A disease burden and economic impact model was populated with the Egyptian national screening and treatment programme data to assess direct medical costs, health effects measured in disability-adjusted life years and the incremental cost-effectiveness ratio. The scenario was compared to a historical base case, which assumed that no programme had been conducted. RESULTS: Total number of viremic cases is expected to decrease in 2030 by 86% under the national screening and treatment programme, versus by 41% under the historical base case. Annual discounted direct medical costs are expected to decrease from $178 million in 2018 to $81 million by 2030 under the historical base case, while annual direct medical costs are estimated to have peaked in 2019 at $312 million before declining to $55 million by 2030 under the national screening and treatment programme. Under the programme, annual disability-adjusted life years are expected to decline to 127 647 by 2030, leading to 883 333 cumulative disability-adjusted life years averted over 2018-2030. CONCLUSIONS: The national screening and treatment programme is highly cost-effective by the year 2021, cost-saving by 2029 and expected to save about $35 million in direct costs and $4705 million in indirect costs by 2030.

Evolution of liver fibrosis after interferon-based anti-hepatitis C virus therapy failure in 3,049 chronic hepatitis C patients without cirrhosis.

BACKGROUND AND STUDY AIMS: Liver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart. PATIENTS AND METHODS: This was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs. RESULTS: A total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [-0.98 (2.93), p ≤ 0.001]. CONCLUSION: Fibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.

Lymphoepithelioma-like Hepatocellular Carcinoma: a Case Report and Review of Literature.

We report a case of hepatic lymphoepithelioma-like carcinoma-hepatocellular carcinoma subtype (LEL-HCC) in a 41-year-old man with chronic hepatitis C virus (HCV) infection. The patient presented with abdominal pain and further assessment revealed a hypoechoic mass on ultrasonography. Serum alpha-fetoprotein (AFP) was 13·6 ng/dl. The patient was diagnosed as hepatocellular carcinoma based on the established triphasic computed tomography (TCT) diagnostic criteria and he underwent a surgical resection of the mass. Microscopic examination showed sheets and cords of malignant epithelial cells intermixed with heavy lymphoid infiltrate, with more than 100 tumor-infiltrating lymphocytes (TILs) per 10 high-power-field (HPF). Based on immunohistochemical studies, the malignant cells were positive for Hep Par 1 and glypican 3, focally positive for cytokeratin 7 (CK7), and negative for cytokeratin 20 (CK20). TILs were diffusely positive for cluster of differentiation 3 CD3 with an approximately equal CD4/CD8 ratio. The patient was recurrence free at 25 months after surgery, as evident by CT and serum alpha-fetoprotein level. LEL-HCC is a rare variant of HCC with a relatively better prognosis. Exploring the potential for immune modulator-based therapy in this subset of tumors is highly recommended.

Seroprevalence of HBV/HCV coinfection among patients with HCV screened during the national campaign for HCV eradication in Egypt.

BACKGROUND AND STUDY AIMS: Little is known about the true prevalence of hepatitis B virus (HBV) coinfection in patients with hepatitis C virus (HCV). This multicenter nationwide study aimed to assess the seroprevalence of HBV among Egyptian patients with HCV and its possible risk factors. PATIENTS AND METHODS: This is a cross-sectional, multicenter, nationwide study. Data were extracted from the National Network of Viral Hepatitis Treatment Centers database. Baseline data of patients proved to be viremic during the national campaign for HCV eradication (October 2018-April 2019) were retrieved. Data included demographics, laboratory tests (HBsAg, CBC, liver biochemical profile, creatinine, AFP, HbA1c, and viral load), FIB-4 score calculation, and abdominal ultrasound results. RESULTS: Results of 297,965 patients showed that HBsAg was positive in 2,347 (0.8%) patients. Patients with HBV/HCV were 57% females and had a mean age of 51 ± 13 years. Patients with positive HBsAg showed significantly more tobacco consumption, intravenous drug abuse, hypertension, and diabetes. No significant difference was noted in HCV viremia between patients with HCV and those with HBV/HCV. Only 14% of patients with HBV/HCV had cirrhosis compared with the 9% of those with HCV; two of them had HCC. CONCLUSION: Although Egypt has a heavy HCV burden, the overall prevalence of HBV is low among patients with HCV infection. Comorbid conditions seem to favor coinfection.

Prevalence and clinical characteristics of patients with metabolic dysfunction-associated fatty liver disease with hepatitis C virus infection-a population-based study.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) was proposed in 2020 to identify fatty liver disease associated with metabolic risks. Metabolic abnormalities with hepatitis C virus (HCV) and MAFLD frequently co-exist. However, data on the co-existence are still lacking. AIM: To explore the prevalence and characteristics of metabolic profiles among a large cohort of patients with HCV infection between 2007 and 2020 based on new diagnostic criteria METHODS: We recruited 288,222 patients with chronic HCV infection with demographic data, laboratory parameters, and ultrasound from a web-based registry of the National Committee for Control of Viral Hepatitis in Egypt from 2007 to 2020. RESULTS: Among the participants, 41.9% (95% CI: 41.69-42.05) met diagnostic criteria for MAFLD, with a significant increase in the period 2014-2020 compared to 2007-2013 (43.3% vs. 19%, respectively). Participants with MAFLD had a high prevalence of obesity, diabetes mellitus and hypertension. The prevalences increased significantly over time (obesity: 66.7% vs. 76.9%, p < 0.01; diabetes mellitus: 14.6% vs. 31.5%, p < 0.01; hypertension: 0.9% vs. 7.6%, p < 0.01; prediabetes: 28.8% vs. 25.9%, p < 0.01) for the periods 2007-2013 and 2014-2020, respectively. The percentage of advanced fibrosis by fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) was significantly higher in participants with MAFLD during 2014-2020 than during 2007-2013 (FIB-4; 18.4% vs. 8% and NFS; 17.1% vs. 7%). CONCLUSION: MAFLD is highly prevalent in patients with HCV infection and has risen over time. This rising prevalence parallels the alarming rise in obesity, diabetes mellitus and hypertension. Early detection of metabolic dysfunction in patients with HCV infection is recommended to prevent MAFLD progression.

International multicenter validation of GES score for HCC risk stratification in chronic hepatitis C patients.

We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6-7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12,038 patients with chronic HCV were analyzed in this study, of whom 11,202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and log-rank tests. The performance of the GES score was evaluated using Harrell's C-index (HCI). The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (p < .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs.

Optimized Systematic Review Tool: Application to Candidate Biomarkers for the Diagnosis of Hepatocellular Carcinoma.

This review aims to develop an appropriate review tool for systematically collating metabolites that are dysregulated in disease and applies the method to identify novel diagnostic biomarkers for hepatocellular carcinoma (HCC). Studies that analyzed metabolites in blood or urine samples where HCC was compared with comparison groups (healthy, precirrhotic liver disease, cirrhosis) were eligible. Tumor tissue was included to help differentiate primary and secondary biomarkers. Searches were conducted on Medline and EMBASE. A bespoke "risk of bias" tool for metabolomic studies was developed adjusting for analytic quality. Discriminant metabolites for each sample type were ranked using a weighted score accounting for the direction and extent of change and the risk of bias of the reporting publication. A total of 84 eligible studies were included in the review (54 blood, 9 urine, and 15 tissue), with six studying multiple sample types. High-ranking metabolites, based on their weighted score, comprised energy metabolites, bile acids, acylcarnitines, and lysophosphocholines. This new review tool addresses an unmet need for incorporating quality of study design and analysis to overcome the gaps in standardization of reporting of metabolomic data. Validation studies, standardized study designs, and publications meeting minimal reporting standards are crucial for advancing the field beyond exploratory studies.

Case study of hepatitis C virus control in Egypt: impact of access program.

BACKGROUND: Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure more than 4 million chronically infected patients. PURPOSE: This is a small tribute to John Martin. METHODOLOGY AND CONCLUSION: Here I present a summary of the HCV problem in Egypt, and how we, through Gilead's Access program under his leadership, were able to eliminate the disease.

Egyptian revalidation of non-invasive parameters for predicting esophageal varices in cirrhotic patients: A retrospective study.

BACKGROUND AND STUDY AIMS: In resource-limited countries, non-invasive tests for assessing liver fibrosis are a potential alternative to costly endoscopic screening for esophageal varices. We aimed to validate several non-invasive parameters for predicting the presence of varices. PATIENTS AND METHODS: Between September 2006 and August 2017, a total of 46,014 patients who underwent upper gastrointestinal endoscopy as one of the perquisites for receiving hepatitis C virus (HCV) therapy were enrolled and divided into group I (without varices) and group II (with varices). Non-invasive parameters of fibrosis, namely Lok index, Bonacini score, liver stiffness, FIB-4, Baveno, and extended Baveno criteria, were validated. RESULTS: Lok index, Bonacini score, liver stiffness, and FIB-4 had areas under the receiver operating characteristic curve (AUCs) of >0.6 (all P < 0.01 for the null hypothesis that the AUC was 0.5) for determination of the presence/absence of varices, with cutoff values of 0.80, 6.5, 21.9 kPa, and 2.94, and sensitivities of 74%, 74%, 66%, and 83%, respectively. The expanded Baveno VI criteria performed better than the Baveno VI criteria (spared endoscopy rate 81% versus 63%). CONCLUSION: The use of non-invasive methods is of limited value in predicting esophageal varices. The limited accuracy of ≤60% may delay the use of appropriate primary prophylaxis against variceal bleeding in a large proportion of cirrhotic patients.

The egyptian clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.

The landscape of chronic liver disease in Egypt has drastically changed over the past few decades. The prevalence of metabolic-associated fatty liver disease (MAFLD) has risen to alarming levels. Despite the magnitude of the problem, no regional guidelines have been developed to tackle this disease. This document provides the clinical practice guidelines of the key Egyptian opinion leaders on MAFLD screening, diagnosis, and management, and covers various aspects in the management of MAFLD. The document considers our local situations and the burden of clinical management for the healthcare sector and is proposed for daily clinical practical use. Particular reference to special groups was done whenever necessary.

Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma.

BACKGROUND: There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV. RESEARCH DESIGN AND METHODS: This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein. RESULTS: Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01). CONCLUSION: Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.

Retreatment of Chronic Hepatitis C Infection: Real-World Regimens and Outcomes From National Treatment Programs in Three Low- and Middle-Income Countries.

Access to recommended second-line treatments is limited for patients who fail initial hepatitis C virus (HCV) therapy in low- and middle-income countries. Alternative regimens and associated outcomes are not well understood. Through a pooled analysis of national program data in Egypt, Georgia, and Myanmar, we observed SVR rates >90% for alternative retreatment regimens.

Survival of a case of pre-eclampsia complicated with acute fatty liver of pregnancy and acute pancreatitis.

Acute fatty liver of pregnancy (AFLP) and acute pancreatitis are peculiar complications of pregnancy. When acute pancreatitis occurs co-incidentally with acute fatty liver of pregnancy, mortality is high. Here, we report a case of a 22-year-old lady in her 36th week of gestation, who presented with pre-eclampsia, acute fatty liver of pregnancy and acute pancreatitis. She fulfilled six Swansea criteria for diagnosis of AFLP, and the diagnosis of acute pancreatitis was based on clinical suspicion, elevated pancreatic enzymes and the sonographic appearance of a swollen pancreatic head.

Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis.

BACKGROUND AND AIM: Existing data are controversial regarding the incidence of hepatitis C (HCV)-related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4). METHODS: Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined. RESULTS: The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×103/mL, and high AFP were independent risk factors of developing HCC. CONCLUSION: Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.

Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID-19: A randomized controlled trial.

Only a few treatments are approved for coronavirus disease-2019 (COVID-19) infections, with continuous debate about their clinical impact. Repurposing antiviral treatments might prove the fastest way to identify effective therapy. This trial aimed to evaluate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or ravidasvir (RDV) added to standard care (SOC) for patients with moderate and severe COVID-19 infection. Multicentre parallel randomized controlled open-label trial. One hundred and twenty eligible patients with moderate and severe COVID-19 infection were randomized to one of the study arms. Ten days of treatment with SOF plus DCV or RDV in addition to the standard of care compared to SOC. Follow up in 7 days. Sum of the counted symptoms at 7 and 10 days, mean change in oxygen saturation level, viral negativity, and rate of intensive care unit (ICU) admission. Compared to SOC, the SOF-DCV group experienced a significantly lower sum of the counted symptoms (fever, headache, generalized aches, or respiratory distress) combined with no evidence of deterioration (ICU admission and mechanical ventilation) on Days 7 and 10 of treatment. Oxygen saturation also significantly improved among the SOF-DCV group compared to SOC starting from Day 4. The study also showed positive trends regarding the efficacy of SOF-DCV with a lower incidence of mortality. On the other hand, adding SOF-RDV to SOC did not show significant improvements in endpoints. The results support the efficacy and safety of SOF-DCV as an add-on to SOC for the treatment of moderate to severe COVID-19 infections.