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Background: Although the prevalence and mortality of hepatitis is high in the Asia‐Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART). Methods: Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD‐LITE) cohort, on ART, and with follow‐up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co‐infection if they ever tested positive for HCV antibody (anti‐HCV) or HBV surface antigen (HBsAg), respectively. Results: In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti‐HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti‐HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response. Conclusion: Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment. [ABSTRACT FROM AUTHOR]

Liver cancer is the fifth most common cancer and the second leading cause of malignant death in Asia, and Asia reports 72.5% of the world's cases in 2020. As the most common histological type, hepatocellular carcinoma (HCC) accounts for the majority of incidence and mortality of liver cancer cases. This review presents the changing epidemiology of HCC in Asian countries in recent years. Globally, aged, male and Asian populations remain the group with the highest risk of HCC. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are still the leading risk factors of HCC with a slight decline in most Asian countries, which is mainly attributed to HBV vaccination of newborns, prevention of HCV horizontal transmission and treatment of chronic hepatitis. However, the prevalence of HCC caused by metabolic factors, including metabolic syndrome, obesity and non-alcoholic fatty liver diseases, is increasing rapidly in Asian countries, which may eventually become the major cause of HCC. Excessive alcohol consumption continues to be an important risk factor as the average consumption of alcohol is still growing. Hopefully, great effort has been made to better prevention and treatment of HCC in most Asian regions, which significantly prolongs the survival of HCC patients. Asian countries tend to use more aggressive intervention than European and American countries, but it remains unclear whether this preference is related to a better prognosis. In conclusion, HCC remains a major disease burden in Asia, and the management of HCC should be adjusted dynamically based on the changing epidemiology. [ABSTRACT FROM AUTHOR]

The incidence rate of hepatocellular carcinoma (HCC) is expected to increase, with most cases occurring in Asia. In some parts of Asia, the occurrence of HCC developing from metabolic-related liver disease has markedly increased in recent years, whereas the occurrence of HCC developing from viral-hepatitis-related liver disease has decreased. Advancements in the treatment of HCC over the past few decades has been remarkable, with most treatment strategies to remove or control liver tumours (hepatic resection, local ablation, radiation therapy, transarterial chemoembolisation, hepatic arterial infusion chemotherapy) primarily developing in Asia. In addition, recent progress in systemic therapies has prolonged the prognosis of advanced HCC. Nowadays, six regimens of systemic therapies have become available in most countries, according to phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). In a global randomised phase III trial (IMbrave 150 trial), the most effective of the latest drug designs was newly emerged combination immunotherapy (atezolizumab plus bevacizumab), which has shown significantly prolonged overall survival compared with sorafenib, which was the first-line systemic therapy for more than a decade. Now, the treatment dynamics for HCC are undergoing a major transition as a result of two important changes: the replacement of viral-related HCC by metabolic-related HCC and the emergence of combination immune therapy. [ABSTRACT FROM AUTHOR]

Liver cancer is the fifth most common cancer and the second leading cause of malignant death in Asia, and Asia reports 72.5% of the world's cases in 2020. As the most common histological type, hepatocellular carcinoma (HCC) accounts for the majority of incidence and mortality of liver cancer cases. This review presents the changing epidemiology of HCC in Asian countries in recent years. Globally, aged, male and Asian populations remain the group with the highest risk of HCC. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are still the leading risk factors of HCC with a slight decline in most Asian countries, which is mainly attributed to HBV vaccination of newborns, prevention of HCV horizontal transmission and treatment of chronic hepatitis. However, the prevalence of HCC caused by metabolic factors, including metabolic syndrome, obesity and non‐alcoholic fatty liver diseases, is increasing rapidly in Asian countries, which may eventually become the major cause of HCC. Excessive alcohol consumption continues to be an important risk factor as the average consumption of alcohol is still growing. Hopefully, great effort has been made to better prevention and treatment of HCC in most Asian regions, which significantly prolongs the survival of HCC patients. Asian countries tend to use more aggressive intervention than European and American countries, but it remains unclear whether this preference is related to a better prognosis. In conclusion, HCC remains a major disease burden in Asia, and the management of HCC should be adjusted dynamically based on the changing epidemiology. [ABSTRACT FROM AUTHOR]

The incidence rate of hepatocellular carcinoma (HCC) is expected to increase, with most cases occurring in Asia. In some parts of Asia, the occurrence of HCC developing from metabolic‐related liver disease has markedly increased in recent years, whereas the occurrence of HCC developing from viral‐hepatitis–related liver disease has decreased. Advancements in the treatment of HCC over the past few decades has been remarkable, with most treatment strategies to remove or control liver tumours (hepatic resection, local ablation, radiation therapy, transarterial chemoembolisation, hepatic arterial infusion chemotherapy) primarily developing in Asia. In addition, recent progress in systemic therapies has prolonged the prognosis of advanced HCC. Nowadays, six regimens of systemic therapies have become available in most countries, according to phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). In a global randomised phase III trial (IMbrave 150 trial), the most effective of the latest drug designs was newly emerged combination immunotherapy (atezolizumab plus bevacizumab), which has shown significantly prolonged overall survival compared with sorafenib, which was the first‐line systemic therapy for more than a decade. Now, the treatment dynamics for HCC are undergoing a major transition as a result of two important changes: the replacement of viral‐related HCC by metabolic‐related HCC and the emergence of combination immune therapy. [ABSTRACT FROM AUTHOR]

Clinical and patient-reported outcomes from patients with nonalcoholic fatty liver disease across the world: data from the Global Non-alcoholic Steatohepatitis (NASH)/Non-alcoholic Fatty Liver Disease (NAFLD) Registry [published online ahead of print November 9, 2021]. NAFLD IN ASIAN CHILDREN A systematic review and meta-analysis included populations comprising 20 595 Asian children demonstrated an overall NAFLD prevalence of 5.53%, and 36.64% children with NAFLD had an elevation of ALT.19 The prevalence of NAFLD increased from 4.4% to 7.1% before and after 2010. The pooled percentage of NASH and advanced fibrosis in nonobese NAFLD was 42.9% and 20.6%, respectively.16 According to an international registry study in Asia, there were 21.6% nonobese individuals among 1812 biopsy-proven NAFLD patients across nine countries.18 Nonobese patients with NAFLD had lower proportions of NASH (50.5% vs 56.5%) and advanced fibrosis (14.0% vs 18.7%) than obese patients with NAFLD. According to the Global Burden of Chronic Disease study, the global hepatocellular carcinoma (HCC) and cirrhosis-related deaths have increased by 11.4% from 2012 to 2017.1 Although chronic hepatitis B (CHB) and hepatitis C remain the most common causes of liver-related deaths, nonalcoholic fatty liver disease (NAFLD) has emerged as the most rapidly growing etiology of liver mortality and morbidity worldwide.1 The global prevalence of NAFLD is around 25% in the general population, with the spectrum from simple fatty liver (SFL) to nonalcoholic steatohepatitis (NASH), and related cirrhosis and HCC. [Extracted from the article]

Asia has a very high burden of acute hepatitis; thus, a comprehensive study of the current burden and long-term trends of acute hepatitis in Asia is needed. We aimed to assess the current status and trends from 1990 to 2019 of acute hepatitis burden in Asia, using the data from the Global Burden of Diseases Study 2019 (GBD 2019) results. Methods: We used the data from the GBD 2019. Absolute death, incidence, and disability adjusted life years (DALY) number and rate of acute hepatitis in Asia were derived from the database from 1990 to 2019. Age-standardized mortality, incidence and DALY rates (ASMR, ASIR and ASDR) were used to compare populations in different regions and times. The estimated annual percentage change (EAPC) in the rates quantified the trends of the acute hepatitis burden. Results: From 1990 to 2019, the ASMR and ASDR of acute hepatitis decreased significantly at different paces, with the largest decrease in acute hepatitis C and the smallest in acute hepatitis E. The ASIR of acute hepatitis decreased relatively slowly, by an average of 0.06% (95% CI, 0.05–0.08%) per year in acute hepatitis A, 0.91% (0.64–1.18%) per year in acute hepatitis C and 0.26% (0.24–0.28%) per year in acute hepatitis E; while the ASIR of acute hepatitis B decreased by an average of 1.95% (1.08–2.11) per year. From 1990 to 2019, the incidence rate of acute hepatitis A increased in most age groups (from the age of 5 to 70), with the 50–55 years group having the fastest increase by an average of 1.81% (95% CI, 1.67–1.95%) per year. In 2019, Afghanistan had the highest ASMR (10.44 per 100,000) and ASDR (357.85 per 100,000) of acute hepatitis, and the highest ASIR was in Mongolia (4703.14 per 100,000). Conclusions: In Asia, the burden of acute viral hepatitis was at a relatively high level, compared with the other four continents. International cooperation and multifaceted and multisectoral actions are needed for Asian countries to eliminate viral hepatitis and to contribute to the global elimination of viral hepatitis. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world. This review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity. Interventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC. [ABSTRACT FROM AUTHOR]

Objectives: The study evaluates the trend over time and the results of serological screening for hepatitis C infection in pregnancy and obstetric and neonatal outcomes.Study Design: It is a retrospective observational study of all pregnant women delivered in maternity units in Trento province, North East Italy, between 2009-2018. Serological screening data for hepatitis C virus were collected through the birth attendance certificate that is the mandatory tool in Italy for the birth report and the monitoring of the pregnancy, childbirth and health of the newborn. We also used the informations collected in the Hospital information system in order to get, for confirmed positive cases, the data of the entire serological profile. On this basis, we calculated the coverage of serological screening, the seroprevalence of the infection and the obstetric and neonatal outcomes.Results: A total of 45,493 pregnant women were analysed, 75.5% Italians and 24.5% foreigners. The mean coverage for serological HCV screening in pregnancy was 99.4%. 177 women tested positive for HCV antibodies (107 Italian and 70 foreign women). Mean overall seroprevalence in pregnant women was 3.9‰ (95% CI: 3.8-4.0); amongst Italians it was 3.2‰ (95% CI: 3.0-3.4) and amongst foreigners it was 6.1‰ (95% CI: 5.9-6.2). The highest seroprevalence was recorded in mothers coming from Asian countries. HCV positive mothers present an excess risk for intrahepatic cholestasis and gestational diabetes compared to HCV negative mothers. The neonatal outcomes considered bring to light a statistically significant increase in preterm births, low birth weight, elective Caesarean births, hospitalisation at birth and bottle- or mixed-feeding vs breast-only feeding. There are differences in obstetric and neonatal outcomes in relation to the HCV positive subgroup of the mother defined in particular by exposure to smoke and/or opioids.Conclusions: The availability and integration of current information sources allows you to verify compliance with national recommendations on the serological screening of hepatitis C virus infection, to determine infection seroprevalence, the characteristics of the cases and the obstetric and neonatal outcomes. Only part of the maternal and neonatal outcomes studied can be attributed to the presence of HCV. [ABSTRACT FROM AUTHOR]

Background and Aim: Infection with hepatitis C virus (HCV) genotype (GT) 6 is uncommon in Taiwan, and reports of ledipasvir/sofosbuvir (LDV/SOF) treatment for GT6 are few. This study evaluates the effectiveness and safety of LDV/SOF in treating chronic hepatitis C (CHC) patients with GT6 infection. Methods: CHC patients that were infected with GT6 and treated for 12 weeks with LDV/SOF at two hospitals were enrolled. All patients were followed for an additional 12 weeks after the completion of LDV/SOF treatment. Demographics, HCV viral load, lipid and sugar profiles, and adverse events were recorded and reviewed. Results: A total of 127 patients were enrolled. Cirrhosis was found in 68.2% of them. Sustained virological response (SVR), determined by per‐protocol analysis, was 97.6%. The SVR rates for cirrhosis versus non‐cirrhosis (96.5% vs 100%, P = 0.229) and low versus high viral load (cutoff value: 106 IU/mL; 100% vs 95.6%, P = 0.108) were similar. Following HCV clearance, significantly lower glycosylated hemoglobin was present both in patients with or without diabetes mellitus. Twenty‐three (18.1%) patients exhibited adverse events, and each adverse event presented with an incidence of 0.8% to 3.1%. Neuropsychiatric symptoms were the most common. During treatment, 18 patients (14.2%) had alanine aminotransferase elevations consistent with more than grade 1 abnormalities, and none had signs of decompensation. Renal function remained unchanged. Conclusion: The high SVR and excellent safety of LDV/SOF treatment for GT6 CHC patients suggest that LDV/SOF is a favorable option for treating GT6 CHC patients in Taiwan and Asia. [ABSTRACT FROM AUTHOR]

Background: Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort.Methods: Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score.Results: A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001).Conclusions: The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy. [ABSTRACT FROM AUTHOR]

Aims: To investigate the relationship between HbA1c and glucose in people with co‐existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease. Methods: HbA1c and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non‐alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non‐cirrhotic portal hypertension and α‐1‐antitrypsin‐related disease. Results: The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49–63) years compared to 60 (50–71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro‐Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA1c was 41 (32–56) mmol/mol [5.9 (5.1–7.3)%] vs 61 (52–70) mmol/mol [7.7 (6.9–8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0–11.2) mmol/l vs 7.3 (5.2–11.5) mmol/l (P=0.17). HbA1c was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α‐1‐antitrypsin disorder. Those with cirrhosis and depressed HbA1c had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA1c (r=–0.28 and r=–0.26, respectively) in the diabetes group with cirrhosis. Conclusion: HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation. What's new?: HbA1c may not be an accurate reflection of blood glucose for the diagnosis/monitoring of diabetes in people with other illnesses or on certain drugs; people with diabetes and liver disease awaiting transplantation are one such group.HbA1c was found to be depressed relative to random plasma glucose by 20 mmol/mol in people with diabetes and cirrhosis (n = 28) compared to people with diabetes but no liver disease (n = 125); however, HbA1c was elevated in one person with cirrhosis attributable to α‐1‐antitrypsin disorder.Compromised HbA1c may be related to haematological differences associated with liver disease involving erythrocyte half‐life, with shorter/longer times giving less/more opportunity for glycation of haemoglobin. [ABSTRACT FROM AUTHOR]

This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored. [ABSTRACT FROM AUTHOR]

Objectives: With earlier antiretroviral therapy (ART) initiation, time spent in HIV care is expected to increase. We aimed to investigate loss to follow‐up (LTFU) in Asian patients who remained in care 5 years after ART initiation. Methods: Long‐term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression. Results: Under the 12‐month definition, the LTFU rate was 2.0 per 100 person‐years (PY) [95% confidence interval (CI) 1.8–2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub‐hazard ratio (SHR) 1.64; 95% CI 1.17–2.31] compared with 31–40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16–2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06–2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self‐reported adherence ≥ 95%, and in those living in high‐income countries. The 6‐month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9–3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006–2009: SHR 2.38; 95% CI 1.93–2.94; and 2010–2011: SHR 4.26; 95% CI 3.17–5.73) compared with 2003–2005. Conclusions: The long‐term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6‐month analysis, but not the 12‐month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the leading causes of cancer-related mortality around the world. Hepatocellular carcinoma (HCC) is the primary cancer of the liver, accounting for the majority of liver cancers. The risk factors associated with HCC include chronic infections with HBV and HCV, alcoholic liver disease, and nonalcoholic fatty liver disease. Additionally, male patients have higher risk for than females, and the risk increases with older age. Mortality rates for HCC parallel its increasing incidence rates. In this context, incidence rate for HCC shows geographic variations in different parts of the world and is heavily affected by regional differences in risk factor for liver disease. The highest incidence rates for HCC are observed in Asia and Africa, while Europe and North America have lower rates. In fact, HBV is still regarded as the leading cause of HCC globally, while HCV is the most common cause of HCC in the USA. Recently, it has been suggested that HCC cases related to nonalcoholic fatty liver disease is on the rise, while the proportion of HCC attributed to alcoholic liver disease remains stable. [ABSTRACT FROM AUTHOR]

Aim: Sustained suppression of hepatitis B surface antigen (HBsAg) production after interferon (IFN) treatment has not been reported for children with genotype C chronic hepatitis B virus (HBV) infection, which is prevalent in Asia. Among children with hepatitis B envelope antigen‐positive genotype C chronic HBV infection, we compared the efficacy of combination therapy with nucleotide analogues and IFN‐α in 11 children with 12 historical cases treated with IFN monotherapy. Methods: The combination of lamivudine and conventional IFN‐α was introduced for the first three patients; the other eight patients were treated with entecavir and pegylated IFN. Results: Demographic factors as well as baseline HBsAg titers and HBV‐DNA levels were similar between the two groups. In the combination therapy group, viral loads were suppressed in 9/11 to below 4.0 log copies/mL both at the end of the therapy (EOT) and at 6 months after EOT. In contrast, in the IFN monotherapy group, suppression of viral loads was observed in 2/12 and 3/12 at EOT and at 6 months after EOT, respectively. In the combination therapy group, HBsAg titers dropped from 4.03 at pretreatment to 2.91 log IU/mL at 6 months after EOT with 4/11 showing a drop to below 1000 IU/mL (one patient achieved HBsAg clearance). In contrast, the amount of HBsAg did not change during the corresponding periods in the IFN monotherapy group. Conclusions: Our preliminary results suggest that combination therapy might be effective in the suppression of HBsAg production as well as HBV‐DNA production for children with genotype C chronic HBV infection. [ABSTRACT FROM AUTHOR]

Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV) infection (frequent in Asia and Africa), hepatitis C virus (HCV), chronic alcohol abuse, or metabolic syndrome (frequent in Western countries). In cirrhosis, hepatocarcinogenesis is a multi-step process where pre-cancerous dysplastic macronodules transform progressively into HCC. The patterns of genomic alterations observed in these tumors were recently identified and were instrumental for the identification of potential targeted therapies that could improve patient care. Liver cancer stem cells are a small subset of undifferentiated liver tumor cells, responsible for cancer initiation, metastasis, relapse and chemoresistance, enriched and isolated according to immunophenotypic and functional properties: cell surface proteins (CD133, CD90, CD44, EpCAM, OV-6, CD13, CD24, DLK1, α2δ1, ICAM-1 and CD47); the functional markers corresponding to side population, high aldehyde dehydrogenase (ALDH) activity and autofluorescence. The identification and definition of liver cancer stem cells requires both immunophenotypic and functional properties. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over 50% of HCV patients worldwide live in the region, where HCV genotypes 1b, 2, 3, and 6 are the most prevalent. Treatment outcomes for chronic hepatitis C vary by ethnicity, and Asian patients achieve higher sustained virologic response rates following interferon (IFN)-based therapy than non-Asians. However, low efficacy, poor safety profile, and subcutaneous administration limit the use of IFN-based therapies. Superior virologic outcomes have been observed with different classes of direct-acting antivirals (DAAs) alone or in combination, and several all-oral DAA regimens are available in Asia. These regimens have shown excellent efficacy and favorable tolerability in clinical trials, yet there is a need for further studies of DAAs in a real world context, particularly in Asia. Furthermore, IFN-free treatment may not be accessible for many patients in the region, and IFN-based regimens remain an option in some countries. There is a need to improve current clinical practices for HCV management in Asia, including effective screening, disease awareness, and prevention programs, and to further understand the cost-effectiveness of IFN-free regimens. The evolution of potent treatments makes HCV eradication a possibility that should be available to all patients. However, access to these therapies in Asian countries has been slow, primarily because of economic barriers that continue to present a hurdle to optimal treatment. [ABSTRACT FROM AUTHOR]

The World Health Organization estimates that 170 million persons are infected with HCV worldwide, but only 22 million are from the Americas and Europe, compared to 94 million from Asia. HCV prevalence in the general US population is 1.6 %, but data for Asian Americans are limited. Our goal was to examine HCV prevalence in Asian Americans in a large ethnically diverse patient cohort seeking primary care at a free clinic in Northern California. A total of 1347 consecutive patients were seen from September 2009 to October 2012 and were studied via individual chart review using case report forms. HCV infection was defined as positive HCV antibody (anti-HCV) or HCV RNA by PCR. 699 out of 1347 patients were screened for HCV. Asian Americans comprised 57.2 % of these patients and 29 (4.1 %) patients tested positive for HCV. Of these 29 HCV-positive patients, 22 (75.9 %) were Asian, yielding a prevalence of 5.5 % for Asians and 2.3 % for non-Asians ( P = 0.038). The highest HCV prevalence was seen in Vietnamese patients at 7.9 %, and 6.0 % in Chinese patients. Of the HCV-positive Asians, none had a history of intravenous drug use (IVDU), tattoos, or sexual exposure. On multivariate analysis, significant independent predictors for positive HCV infection were male gender (OR 2.53, P = 0.02) and presence of known risk factors (OR 21.1, P < 0.001). However, older age and Asian ethnicity were found to be significant predictors of HCV infection (OR 1.03, P = 0.05 and 2.31, P = 0.066, respectively). In our study, HCV prevalence in patients seeking routine primary care was 5.5 % in Asian Americans, which was over double the prevalence for non-Asians at 2.3 %. Known risk factors were also notably absent in Asian patients with HCV infection. The high prevalence of HCV in Asian-Americans is likely reflective of the higher prevalence of HCV in their countries of origin in Asia. Asian-Americans immigrants from endemic countries are at higher risk of HCV infection and should be screened for HCV, regardless of their exposure risk profile. [ABSTRACT FROM AUTHOR]

Background: Single-nucleotide polymorphisms (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene correlate with ribavirin (RBV)-induced anemia in patients with chronic hepatitis C (CHC) receiving combination therapy. Managing anemia is an early priority in the treatment process. Objectives: The aim was to develop a predictive index based on ITPA SNP status to identify CHC patients at risk of anemia. Patients and Methods: A total of 418 eligible East Asian patients diagnosed with CHC genotype 1 (G1) received combination therapy in this study. Participant DNA was genotyped for a functional ITPA SNP (C/C, A/A or C/A) on chromosome 20 at rs1127354. A predictive index was constructed by incorporating independent factors identified for severe anemia events (hemoglobin < 10 g/dL). Areas under the receiveroperating characteristic curves (AUCs) represented the diagnostic accuracies of the predictive index in randomly assigned development and validation cohorts. Results: Multiple logistic regressions identified age (≥ 50 y: OR = 9.7, 95% CI = 5.0 - 18.6), ITPA rs1127354 (C/C: OR = 3.3, 95% CI = 1.8 - 5.8) and baseline hemoglobin (< 14.0 g/dL: OR 6.4, 95% CI = 3.3 - 12.1; 14.0 - 14.9: OR = 2.4, 95% CI = 1.2 - 4.6) as predictors of severe anemia throughout the treatment. For severe anemia, the predictive index incorporating age, ITPA SNP status and baseline hemoglobin yielded diagnostic accuracies (AUCs) of 0.830 (95% CI = 0.783 - 0.871) in the development (n = 324) and 0.902 (0.826 - 0.925) in the validation (n = 81) cohorts. Conclusions: In patients with CHC G1 and receiving combination therapy, ITPA SNP-based index was an accurate and practical solution for prediction of severe anemia. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV).Methods. Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria.Results. The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers.Conclusion. Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease. [ABSTRACT FROM PUBLISHER]

Background & Aims: The World Health Organisation (WHO) Prevention & Control of Viral Hepatitis Infection: Framework for Global Action offers a global vision for the prevention and control of viral hepatitis. In October 2012, the Coalition to Eradicate Viral Hepatitis in Asia Pacific (CEVHAP) organised the North Asia Workshop on Viral Hepatitis in Taipei to discuss how to implement the WHO Framework in the North Asia region. This paper presents outcomes from this workshop. Methods: Twenty-eight representatives from local liver associations, patient organisations, and centres of excellence in Hong Kong, Japan, Korea, and Taiwan participated in the workshop. Findings: Priority areas for action were described along the four axes of the WHO Framework: (1) awareness, advocacy and resources; (2) evidence and data; (3) prevention of transmission; and (4) screening and treatment. Priorities included: axis 1: greater public and professional awareness, particularly among primary care physicians and local advocacy networks. Axis 2: better economic data and identifying barriers to screening and treatment uptake. Axis 3: monitoring of vaccination outcomes and targeted harm reduction strategies. Axis 4: strengthening links between hospitals and primary care providers, and secure funding of screening and treatment, including for hepatocellular carcinoma. Conclusions: The WHO Framework provides an opportunity to develop comprehensive and cohesive policies in North Asia and the broader region. A partnership between clinical specialists, primary care physicians, policy makers, and people with or at risk of viral hepatitis is essential in shaping future policies. [Copyright &y& Elsevier]

Abstract: Background: Clinical outcomes of heart transplantation (HTx) among recipients with chronic hepatitis C virus (HCV) infection are poorly understood especially in Asia. Therefore, this study evaluated these clinical outcomes. Methods: Using retrospective chart review we collected data on 385 patients including 20 HCV-positive recipients at the time of transplantation. We obtained information on demographics features, serial transaminases, graft function, patient survival as well as the incidences of acute hepatitis and transplant coronary artery disease. Results: Between 1987 and 2010, the 20 HCV-positive patients had a median age at transplantation of 52 years (range, 30–63). Seventeen were men and three women. All the patients were classified as Child-Pugh class A; two had cirrhosis prior to HTx. Over a mean follow-up of 63 months (range, 2 days to 187 months), there were 11 deaths, including two hospital mortalities and nine subsequent deaths. Only one mortality (5%) was related to Child-Pugh class C cirrhosis, despite liver transplantation. Among the other 19 deceased or surviving recipients, there was no evidence of hepatic dysfunction or hepatocellular carcinoma. Transplant coronary artery disease was detected in six patients (30%). There was no significant difference in Kaplan-Meier actuarial survival between the HCV-positive and HCV-negative recipients (P = .59). Conclusions: There was no significant difference in patient survival or graft function between HCV-positive and HCV-negative HTx recipients. Additionally, HCV-positive recipients were not at an increased risk of hepatic failure or accelerated transplant coronary artery disease. [Copyright &y& Elsevier]

The incidence of HCC is rising worldwide. Studies on ethnicity-based clinical presentation of HCC remain limited. The aim is to compare the clinical presentation and stage of HCC between Asian-Americans and non-Asian-Americans. This retrospective study assessed ethnicity-based differences in HCC presentation, including demographics, laboratory results, diagnosis of underlying liver disease, and stage of HCC. Of 276 patients, 162 were Asian-Americans and 114 were non-Asian-Americans. Compared to non-Asian-Americans, Asian-Americans had a significantly higher incidence of history of hepatitis B virus (HBV) infection (55.0% vs. 4.9%, P < 0.001), family history of HBV infection (12.5% vs. 0.0%, P < 0.001) and HCC (15.2% vs. 2.9%, P = 0.002), but lower incidence of history of hepatitis C virus (HCV) infection (37.5% vs. 61.6%, P < 0.001). At diagnosis of HCC, Asian-American patients had a significantly lower frequency of hepatic encephalopathy (8.9% vs. 29.3%, P = 0.001), and ascites (26.7% vs. 57.3%, P < 0.001). Asian-Americans had lower Child-Pugh scores (class A: 62.0% vs. 31.4%, P < 0.001), and MELD scores (9.2 ± 4.4 vs. 12.0 ± 6.4, P = 0.02), and presented with a lower stage of HCC by Okuda staging (I: 43.8% vs. 22.8%, P = 0.001). Asian-American patients with HCC presented with a higher incidence of history and family history of HBV infection, lower incidence of hepatic decompensation, lower Child and MELD scores, and an early stage HCC disease. [ABSTRACT FROM AUTHOR]

Background & Aims: There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy. Methods: Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5μg/kg/wk) for 24weeks (group A); peginterferon alfa-2b (1.0μg/kg/wk) for 24weeks (group B); or peginterferon alfa-2b (1.5μg/kg/wk) for 16weeks (group C), each in combination with weight-based ribavirin (800–1200mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR). Results: The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similar in Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms. Conclusions: For patients with chronic hepatitis C genotype 2/3 infection, 24weeks of peginterferon alfa-2b (1.5μg/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment. [ABSTRACT FROM AUTHOR]

The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. Data references were identified through indexed journals and non-indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. We estimated that 49.3-64.0 million adults in Asia, Australia and Egypt are anti-HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection. [ABSTRACT FROM AUTHOR]

The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24 weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR) > 2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2] = 171, HCV-3 = 92), and 433 non-Asian region patients (407 'Caucasian'); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis) = 201 (77%) and F2-F4 (significant fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 = 64 (25%), grade 2/3 = 27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38%) patients had HOMA-IR > 2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR] = 8.42), necro-inflammatory grade (OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN α-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 ± 3.73) (day-1, mean ± SD) but lower daily viral production rate (P = 106-1012) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Background/aims: Traditional Chinese herbal therapies are widely used for the treatment of chronic hepatitis C (CHC) in Asia. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing interferon therapies with Chinese herbal therapies and/or interferon plus Chinese herb therapies for the treatment of CHC. Methods: The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database and China Biomedical Database were searched to identify RCTs that evaluated the virological response to interferon therapies, Chinese herbal therapies and interferon plus Chinese herb therapies in CHC patients. We statistically combined data using a random-effect meta-analysis according to the intention-to-treat principle. Results: The literature search yielded 770 studies, and 26 RCTs comprising 1905 patients matched the selection criteria. Overall, the sustained virological response (SVR) was significantly higher in patients treated with interferon plus Chinese herbs than in patients treated with interferon alone (49% vs 33%, relative risk, 1.52; 95% confidence interval: 1.23–1.89; p <0.05). Combined therapies of interferon plus Chinese herb therapies were also superior to interferon therapies alone in achieving the end-of-treatment viral response (ETVR), and resulted in fewer relapses, fewer adverse events and more rapid alanine transaminase normalisation. Interferon therapies achieved higher ETVR than Chinese herbal therapies, but they yielded a similar SVR. Conclusions: The current evidence suggests that combined therapies of interferon plus Chinese herbs yielded a higher SVR, and resulted in fewer relapses and fewer adverse events than interferon therapies. [ABSTRACT FROM AUTHOR]

The article presents a clinical review of hepatocellular carcinoma for the non-specialist. It is cited as the third most common cause of cancer related mortality around the world. Population data from Great Britain indicate that age standardised incidence has risen from 1.4 to 3.9 per 100,000 people between 1975 and 2006. The liver diseases that predispose to hepatocellular carcinoma include hepatitis B in Asia and Africa and hepatitis C in Western countries and Japan. Preventive and treatment options are also discussed. INSET: A PATIENT'S PERSPECTIVE.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The number of new cases is estimated to be 564,000 per year. About 80% of all cases are found in Asia. The goal of MCC management is "cancer control" — a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their family. Overall, 80% of HCC can be attributed to chronic hepatitis B and C infection. Prevention of infection with hepatitis B and C virus is the key strategy to reduce the incidence of HCC in Asia. Liver resection and liver transplantation remain the options that give the best chance of a cure. In the past two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC. Many challenges are still present in Asia, such as the high prevalence of chronic hepatitis, the low resection rate of HCC, the high post-operative recurrence and the severe shortage of cadaveric organ donor. This article aims to discuss the development and challenges in the prevention and management of HCC in Asia. [ABSTRACT FROM AUTHOR]

Abstract Hepatitis C virus (HCV) infection is widespread throughout Asia. Unusual features of HCV in Asia include a novel genotype distribution with a significant representation of 3a. This is particularly important as genotype 3 is very sensitive to interferon-based therapies. A major concern in the Asian region is the high prevalence of hepatocellular cancer complicating HCV-associated cirrhosis, particularly in Japan. Finally, liver transplantation for advanced HCV infection with cirrhosis is an option via cadaveric and living donor programmes. [ABSTRACT FROM AUTHOR]

Abstract The discovery a decade ago of the hepatitis C virus (HCV) led to control of post-transfusion hepatitis in many countries, but raised a number of further questions about the transmission and epidemiological distribution of the newly discovered virus. In some countries, the diagnosis of HCV infection has been designated as a notifiable condition, with doctors (or laboratories, or both) required to send case reports to public health authorities. Such case reports of HCV diagnosis are inevitably biased towards people with symptomatic presentations or a known history of exposure, or those who undergo screening for other purposes, such as blood transfusion. Another approach has been the use of serological prevalence surveys either making use of blood that had been taken or tested for other purposes or recruiting specific population groups for the explicit purpose of measuring HCV prevalence. A limited number of surveys have either attempted to obtain true random samples of geographically defined populations, or recruited subjects, such as pregnant women, who may be considered to be broadly representative of the wider population. Injecting drug use is clearly the main mode of HCV transmission in countries that have established comprehensive blood screening, and it remains a major public health challenge. Although mother-to-child transmission is known to occur with a frequency of about 7% there is no proven means of prevention and very little is known about the long-term consequences of maternally transmitted infection. The conclusion from a number of somewhat conflicting studies is probably that HCV infection should not be viewed as a sexually transmissible infection from the perspective of population health strategies. However, people with HCV infection and their sexual partners should minimize the extent of blood contact that may occur through sexual activity. [ABSTRACT FROM AUTHOR]

Introduction: Sexual acquisition has emerged as a transmission route for hepatitis C virus (HCV) of growing importance among human immunodeficiency virus (HIV)-positive populations. In Western countries, HCV epidemics have been increasingly detected among men who have sex with men (MSM). This review describes the molecular epidemiology of sexually acquired HCV infection in the Asia-Pacific region., Methods: A systematic search was performed on PubMed in March 2019. Either abstract or full-text of each publication in the search results was screened for eligibility. Studies from different countries/cities involving eligible cases, who acquired HCV sexually with identified subtype, were synthesized for the evaluation of molecular epidemiology in the Asia-Pacific region. Two large-scale systematic reviews on the genotype distribution of HCV at a population level and among PWID were used as references for comparison., Results and Discussion: Overall, 13 full-text articles with 549 subjects originating from nine countries/cities were reviewed. A total of five genotypes and 14 subtypes were identified, dominated by subtypes 1b (23.0%), 2a (19.1%) and 3a (29.5%). A majority of the infected cases occurred in HIV-positive MSM. In some places, notably Hong Kong, India and Indonesia, the predominant subtype in sexually acquired HCV infection in MSM was different from that circulating in the general population. Shared transmission networks between people who inject drugs (PWID) and MSM were shown in Australia and New Zealand, whereas overlapping risk elicited from a small number of subjects existed in Tokyo, Taipei and Guangxi. MSM-specific clusters were identified in Hong Kong, Taipei and Hubei., Conclusions: The distribution of sexually acquired HCV was sparsely scattered across countries/cities in the Asia-Pacific region. The threat of overlapping risk differed by locations, whereas transnational outbreaks remained uncommon. The paucity of information has hindered progress with comprehensive assessment in the Asia-Pacific region, where seroprevalence of HCV among HIV-positive MSM was relatively high., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Genetic polymorphism in the interferon lambda (IFN-λ) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to interferon-based treatment. Here, we evaluate associations between IFN-λ polymorphism and HCV variation in 8729 patients (Europeans 77%, Asians 13%, Africans 8%) infected with various viral genotypes, predominantly 1a (41%), 1b (22%) and 3a (21%). We searched for associations between rs12979860 genotype and variants in the NS3, NS4A, NS5A and NS5B HCV proteins. We report multiple associations in all tested proteins, including in the interferon-sensitivity determining region of NS5A. We also assessed the combined impact of human and HCV variation on pretreatment viral load and report amino acids associated with both IFN-λ polymorphism and HCV load across multiple viral genotypes. By demonstrating that IFN-λ variation leaves a large footprint on the viral proteome, we provide evidence of pervasive viral adaptation to innate immune pressure during chronic HCV infection., Competing Interests: NC, JF No competing interests declared, ES, HM, AO, DB, GS, JM This study was partially funded by Gilead Sciences and the author is an employee of Gilead Sciences, SZ has been a consultant for Abbvie, Gilead, Janssen, Merck/MSD, (© 2019, Chaturvedi et al.)

Background: Hepatitis C virus (HCV) genotype 6 (GT 6) is the predominant genotype among certain Asian populations. The availability of newer DAA options is limited in many parts of Asia., Aim: To compare sustained virologic response (SVR-12) rates between ledipasvir and sofosbuvir (LDV+SOF) and velpatasvir+SOF (SOF+VEL) for patients with HCVGT6 infection., Method: Retrospective study of consecutive adult HCVGT6 patients identified via ICD 9 code: 070.5 from United States treatment centers. Treatment was LDV+SOF or SOF+VEL for 8-24 weeks. A 1:1 propensity score matching (PSM) on HCV RNA, cirrhosis, alanine aminotransferase, aspartate aminotransferase, platelets, and fibrosis score was conducted among the treatment-naïve HCVGT6 patients to balance groups and isolate treatment effects., Results: After exclusion criteria, 149 patients remained (n = 135 treatment-naïve; n = 14 treatment-experienced). The mean age was 63.8 ± 10.2 years, 66.9% male, and 93.9% Vietnamese. In treatment-naïve arm, 52.2% LDV+SOF cohort were cirrhotic compared to 11.6% SOF+VEL cohort (P < 0.0001). SVR-12 for LDV+SOF was 96.4% and 100% for the SOF+VEL cohort (P = 0.22). SVR-12 for cirrhotic patients was 95.4% (n = 41/43) for LDV+SOF and 100.0% (n = 5/5) for SOF+VEL (P = 0.62). After PSM (n = 33 per group), LDV+SOF SVR-12 rate was 97.0% compared to SOF+VEL SVR-12 of 100% (P = 0.31). The treatment-experienced group (n = 14), were all treated with LDV+SOF with an SVR-12 of 92.3%., Conclusion: Whether treatment-naïve, treatment-experienced, or cirrhotic patients with HCV GT 6 residing in the US had excellent outcomes when treated with SOF+VEL or LDV+SOF. Since LDV+SOF is more readily available globally, our results may provide clinicians with a treatment option when cost and availability limit the treatment choice., (© 2018 John Wiley & Sons Ltd.)

To estimate HCV seroprevalence in subpopulations of women delivering live-born infants in the North Thames region in England in 2012, an unlinked anonymous (UA) cross-sectional survey of neonatal dried blood spot samples was conducted. Data were available from 31467 samples from live-born infants received by the North Thames screening laboratory. Thirty neonatal samples had HCV antibodies, corresponding to a maternal seroprevalence of 0·095% (95% confidence interval 0·067-0·136). Estimated HCV seroprevalences in women born in Eastern Europe, Southern Asia and the UK were 0·366%, 0·162% and 0·019%, respectively. For women born in Eastern Europe seroprevalence was highest in those aged around 27 years, while in women born in the UK and Asia-Pacific region, seroprevalence increased significantly with age. HCV seroprevalence in UK-born women whose infant's father was also UK-born was 0·016%. One of the 30 HCV-seropositive women was HIV-1 seropositive. Estimated HCV seroprevalence for women delivering live-born infants in North Thames in 2012 (0·095%) was significantly lower than that reported in an earlier UA survey in 1997-1998 (0·191%). Data indicate that the cohort of UK-born HCV-seropositive women is ageing and that, in this area of England, most perinatally HCV-exposed infants were born to women themselves born in Southern Asia or Eastern Europe.

HCV in the East is a complex scenario with prevalence rates of 0.5% to as high as 4.7%, and variable distributions of genotypes, with a dominance of genotype 1b in East Asia, genotype 3 in South Asia and South East Asia, and genotype 6 in Indochina. Approvals for the new oral directing antiviral agents (DAAs), in the East have been very slow, but ultimately will be achieved by 2019, consequently, pegylated interferon and ribavirin are still widely used. Nonetheless the main issues are the problems of screening and linkage to management, and the considerable barriers to access HCV care., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hepatitis C virus (HCV) genotypes' monitoring allows real-time insight into the dynamic changes that occur in the global epidemiological picture of HCV infection. Intravenous drug use is currently the primary driver for HCV transmission in developed and developing countries. The distribution of HCV genotypes/subtypes differs significantly between people who inject drugs (PWID) and the general population. HCV genotypes that previously exhibited a limited geographical distribution (3a, 4) are becoming more prevalent in this high-risk group. Immigration from HCV-endemic countries and the evolving networks of HCV transmission in PWID influence HCV genotypes distribution in Europe. Social vulnerabilities (e.g., unemployment, homelessness, and limited access to social and healthcare insurances systems) are important triggers for illicit drug use, which increases the associated risks of HCV infection and the frequent emergence of less prevalent genotypes. Genotype/subtype determination bears important clinical consequences in the progression of liver disease, susceptibility to antiviral therapies and the emergence of resistance-associated variants. An estimated half of the chronically HCV-infected PWID are unaware of their infection, and only one in ten of those diagnosed enter treatment. Nevertheless, PWID exhibit high response rates to new antiviral regimens, and the level of HCV reinfection is unexpectedly low. The focus of the healthcare system must be on the early detection and treatment of infection, to avoid late presentations that are associated with high levels of viremia and liver fibrosis, which may diminish the therapeutic success rate.

The prevalence of hepatitis C virus (HCV) in Asia is 0.5% to 4.7%, with three different genotypes predominating, depending on the geographic region: genotype 1b in East Asia, genotype 3 in South and Southeast Asia, and genotype 6 in Indochina. Official approval for direct-acting antiviral agents (DAAs) in Asia lags significantly behind that in the West, such that in most countries the mainstay of therapy is still pegylated interferon and ribavirin (PR). Because the interleukin-28B genetic variant, associated with a high sustained virologic response (SVR), is common in Asians, this treatment is still acceptable in Asian patients with HCV infections. A roadmap for HCV therapy that starts with PR and takes into account those DAAs already approved in some Asian countries can provide guidance as to the best strategies for management, particularly of genotype 1 and 3 infections, based on SVR rates. Sofosbuvir and PR are likely to be the initial therapies for genotype 1 and 3 disease, although in the former these drugs may be suboptimal in patients with cirrhosis (62% SVR) and the extension of treatment to 24 weeks may be required. For difficult to treat genotype 3 infections in treatment-experienced patients with cirrhosis, a combination of sofosbuvir and PR result in an 83% SVR and is, therefore, currently the optimal treatment regimen. Treatment failure is best avoided since data on rescue therapies for DAA failure are still incomplete.

Background: Barriers to access medical screening and care may underestimate the number of diseased subjects among immigrant populations., Aims: To evaluate the prevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus infections among immigrants recruited in a disadvantaged area., Methods: The study enrolled all subjects seen between 1999 and 2009 at an on-site health and family counselling centre for immigrants. During the first 6 years of the study a pro-active recruitment was performed using a mobile unit., Results: Overall 2681 subjects were enrolled (median age: 31 years; 52.8% males; 82.3% from Sub-Saharan Africa; 13.9% of the women were sex workers). A total of 206 subjects (7.6%) were hepatitis B surface antigen-positive, 84 (3.6%) were anti-hepatitis C virus-positive, 129 (5%) were anti-human immunodeficiency virus-positive, 84 (3.1%) were drug users, and 436 (16.3%) were alcohol abusers. The prevalence of hepatitis B surface antigen and anti-hepatitis C virus remained consistent throughout the study period, while the prevalence of human immunodeficiency virus significantly decreased. At multivariate analysis, hepatitis B virus infection was associated with male gender, hepatitis C virus infection with drug addiction, and human immunodeficiency virus infection was associated with female gender, drug addiction, and active recruitment., Conclusions: An active recruitment strategy should be considered to reach disadvantaged populations at high risk of human immunodeficiency virus infection., (Copyright © 2013. Published by Elsevier Ltd.)