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The increasing number of direct-acting antiviral (DAA) regimens along with limited number of subjects and co-medications involved in clinical trials results in drug-drug interactions (DDIs) with DAAs is to be determined. We aimed to examine the prevalence and degree of DDIs between DAAs and other co-medications in a territory-wide cohort of chronic hepatitis C virus (HCV) patients.DDIs were assigned to three risk categories: Category 1-no clinically significant DDI; category 2-potential clinically significant interaction (monitoring and caution required); category 3-contraindicated (should not be co-administered).Of 2981 patients (mean age 59.3 ± 12.3 years; male 60.6%), 810 (48.8%) had genotype 1 and 552 (33.2%) genotype 6 HCV among the 1661 patients with HCV genotype tested; 769 (25.8%) received sofosbuvir/velpatasvir, 510 (17.1%) sofosbuvir/ledipasvir, and 865 (29.0%) glecaprevir/pibrentasvir. More than one-fourth (26.3%) of the patients have polypharmacy (≥ 3 co-medications) in all patients, 27.0% in patients received sofosbuvir/velpatasvir, 25.1% in elbasvir/grazoprevir, and 21.2% in glecaprevir/pibrentasvir. 2037 (68.3%) patient experienced DDI (Category 2: 53.1%; Category 3: 15.2%). The commonest drugs leading to DDIs were calcium channel blockers (31.5%) and proton pump inhibitors (23.0%) in category 2; statins (10.2%), antiplatelet/anticoagulants (3.0%) and antipsychotics (2.9%) in category 3. Changing medication was the most common response from physicians in both category 2 and 3 DDIs.The commonest co-medications leading to contraindication during DAA treatment were statins and antipsychotics. Category 2 and 3 DDIs are often managed by appropriate dose adjustments or temporary discontinuation of relevant co-medications. Careful assessment for potential DDI before DAA use is mandatory to avoid potential harmful effects.

The world has made significant progress in developing novel treatments for COVID-19 since the pandemic began. Some treatments target the patient's dysregulated inflammatory response during COVID-19 infection and may cause hepatitis B reactivation (HBVr) in patients with current or past hepatitis B virus (HBV) infection. This review summarizes the risk and management of HBVr due to different treatments of COVID-19 in patients who have current or past HBV infection. Abnormal liver function tests are common during COVID-19 infection. Current evidence suggests that current or past HBV infection is not associated with an increased risk of liver injury and severe disease in COVID-19 patients. Among patients who received high-dose corticosteroids, various immunosuppressive monoclonal antibodies and inhibitors of Janus kinase, the risk of HBVr exists, especially among those without antiviral prophylaxis. Data, however, remain scarce regarding the specific use of immunosuppressive therapies in COVID-19 patients with HBV infection. Some results are mainly extrapolated from patients receiving the same agents in other diseases. HBVr is a potentially life-threatening event following profound immunosuppression by COVID-19 therapies. Future studies should explore the use of immunosuppressive therapies in COVID-19 patients with HBV infection and the impact of antiviral prophylaxis on the risk of HBVr.

We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). This is a retrospective study of 6189 adult treatment-naive CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR

Background & Aim Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. Methods All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. Recommendations We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization’s goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions. We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan–Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria. Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03–1.57% among noncirrhotic males and 2.57–6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment. Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.

Despite HCV cure, patients remain at risk for HCC, but risk factor data for HCC following SVR are limited for Asian patients. To address this gap, we analyzed 5814 patients (5646 SVR, 168 non-SVR) from the Real-World Evidence from the Asia Liver Consortium for HCV (REAL-C) who did not have HCC or a history of HCC at baseline (pre-DAA treatment) and did not develop HCC within 6 months of baseline. To assess the effect of SVR on HCC incidence, we used 1:4 propensity score matching [(PSM), age, sex, baseline cirrhosis, and baseline AFP] to balance the SVR and non-SVR groups. In the PSM cohort (160 non-SVR and 612 SVR), the HCC incidence rate per 100 person years was higher in the non-SVR compared to the SVR group (5.26 vs. 1.94, p

Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs—entecavir and tenofovir disoproxil fumarate (TDF)—Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations—TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.

To provide an updated overview on the current status of risk prediction scores for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus infection. More HCC risk scores have been developed, validated, and optimized (e.g., with liver stiffness measurement) in different patient and ethnic groups. Risk scores for treated patients with high negative predictive values would be able to identify patients who may not need HCC surveillance anymore as their HCC risk has been reduced by antiviral therapy. Current HCC risk scores can accurately predict HCC in specific populations, in both treatment-naive patients and those receiving antiviral therapy. Different levels of care and different intensities of HCC surveillance should be offered according to the risk profile of patients.

One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia. Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR

Background Because of high-risk behaviours, sedentary lifestyle and side effects of medications, psychiatric patients are at risk of viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. We aimed to study the incidence of hepatocellular carcinoma (HCC) and cirrhotic complications in psychiatric patients. Methods We identified consecutive adult patients in all public hospitals and clinics in Hong Kong with psychiatric diagnoses between year 2003 and 2007 using the Clinical Data Analysis and Reporting System, which represents in-patient and out-patient data of approximately 80% of the 7.4-million local population. The patients were followed for liver-related events (HCC and cirrhotic complications) and deaths until December 2017. Age- and sex-standardized incidence ratio (SIR) of HCC in psychiatric patients to the general population was estimated by Poisson model. Results We included 105,763 psychiatric patients without prior liver-related events in the final analysis. During a median (interquartile range) follow-up of 12.4 (11.0–13.7) years, 1461 (1.4%) patients developed liver-related events; 472 (0.4%) patients developed HCC. Compared with the general population, psychiatric patients had increased incidence of HCC (SIR 1.42, 95% confidence interval [CI] 1.28–1.57, P P P P P = 0.047). Liver disease was the fifth most common cause of death in this population, accounting for 595 of 10,614 (5.6%) deaths. Importantly, 569 (38.9%) patients were not known to have liver diseases at the time of liver-related events. The median age at HCC diagnosis (61 [range 26–83] years) was older and the median overall survival (8.0 [95% CI 5.0–10.9] months) after HCC diagnosis was shorter in this cohort of psychiatric patients than other reports from Hong Kong. Conclusions HCC, cirrhotic complications, and liver-related deaths are common in psychiatric patients, but liver diseases are often undiagnosed. More efforts are needed to identify liver diseases in the psychiatric population so that treatments and screening for HCC and varices can be provided to patients in need.

Both chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are frequent liver diseases with substantial morbidity and mortality. How often do these two diseases occur together? Does hepatitis B virus protect or promote concurrent fatty liver? How does concurrent fatty liver influence the clinical outcomes of CHB? We summarized the latest evidence to tackle all these clinically significant questions. Concurrent fatty liver in CHB without significant alcohol intake is a common and increasingly alarming problem. Patients with CHB have a lower chance of fatty liver than the general population, but the underlying mechanism remains to be further explored. Clinical impacts of concurrent fatty liver among CHB patients, in terms of treatment response, fibrosis and cirrhosis progression, liver cancer risk, and mortality, are still debatable. Concurrent fatty liver in CHB is a common and clinically relevant condition.

Approximately one-quarter of patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A hepatocellular carcinoma (HCC) suffer from tumor relapse within the first year after surgical resection. Little data is available for inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), in predicting the clinical outcome of patients with very early/early stage HCC who underwent curative surgery. A retrospective cohort study of 324 patients with BCLC stage 0/A primary HCC undergoing surgical resection was conducted to investigate the prognostic impacts of NLR, PLR, and PNI. The low-PNI group (

Nonalcoholic fatty liver disease (NAFLD) is an evergrowing problem in the developed and developing worlds, affecting 15–40 % of the population [1]. Once regarded as a benign condition, NAFLD is the leading cause of cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma (HCC) [2], and the third most frequent indication for liver transplantation [3]. A key challenge faced by clinicians who manage NAFLD is to establish the diagnosis and to differentiate simple steatosis from advanced disease [4]. Furthermore, steatosis often coexists in other chronic liver diseases such as chronic hepatitis C [5]. Trans-abdominal ultrasonography (USG) is the commonest imaging tool used in the diagnosis of hepatic steatosis, but only with confidence when the amount of fatty infiltration exceeds 33 % [6]. Although proton magnetic resonance spectroscopy (H-MRS) is an accurate and reproducible noninvasive means of quantifying hepatic fat, its availability is limited in many areas [1]. Transient elastography (Fibroscan, Echosens, Paris, France), originally developed for the diagnosis of liver fibrosis and cirrhosis, has been validated in patients with NAFLD [7]. The fundamental technology employed by Fibroscan involves a plastic shear wave that propagates through liver tissue combined with a pulse-echo ultrasound used to follow and measure the velocity of the propagation of the shear wave, which is directly related to tissue stiffness and hence severity of liver fibrosis [8]. Its latest iteration includes the measurement of the controlled attenuation parameter (CAP), a measurement of the attenuation of the forward and return ultrasound signal at 3.5 MHz using signals acquired by the regular M probe of Fibroscan. At a given frequency, the ultrasound-attenuation coefficient can be expressed in dB/m. Since the attenuation of ultrasound signals is greater in fat than in water, CAP may be used to estimate the degree of hepatic steatosis [9]. The diagnostic attractiveness of CAP is that it may be measured concurrently with liver stiffness using the same instrument enabling the simultaneous assessment of hepatic steatosis and fibrosis [8]. Data concerning the accuracy of CAP to diagnosis different degrees of hepatic steatosis are evolving. CAP efficiently detected low-grade steatosis ([10 %), with a sensitivity of 91 % and specificity of 81 % at a cutoff value of 238 dB/m in a retrospective cohort of patients of mixed etiology chronic liver diseases [9]. The accuracy of CAP was confirmed in two prospective studies of mixed etiology liver disease [10, 11], and in single etiology populations, including chronic hepatitis B (CHB), chronic hepatitis C, NAFLD, and alcoholic liver disease [12]. The suggested diagnostic performance and cutoff values for different degrees of steatosis are summarized in Table 1. Nonetheless, data concerning its performance in healthy subjects and patients with CHB were either lacking or insufficient. In this issue of the Digestive Diseases and Sciences, two groups of investigators provide important data to illustrate the accuracy of CAP in these two settings. Chon et al. [16] report CAP data from 264 healthy subjects, either as potential liver donors or in subjects undergoing routine G. L.-H. Wong (&) V. W.-S. Wong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China e-mail: wonglaihung@cuhk.edu.hk

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in many regions, affecting 15–40 % of the general population [1, 2]. One of the key challenges in managing NAFLD is differentiating simple steatosis from advanced disease, i.e., those with nonalcoholic steatohepatitis (NASH), advanced fibrosis or even cirrhosis [3]. The challenge is further substantiated by the poor correlation between liver fibrosis and routine blood tests, e.g., the serum alanine aminotransferase (ALT) level [4]. Patients may have progressed to advanced fibrosis or cirrhosis without any abnormalities in these common blood parameters [5]. Liver biopsy is not always feasible or acceptable to patients, especially to those largely asymptomatic subjects; this has promoted the popularity of noninvasive assessments of liver fibrosis for NAFLD patients (Table 1) [6, 7]. Among the numerous noninvasive assessments, liver stiffness measurement (LSM) by transient elastography is one of the most popular tools [8]. This tool out-performed other serum parameters in detecting advanced fibrosis or cirrhosis [9]. Nonetheless, a false-positive diagnosis of advanced fibrosis is not uncommon, in addition to LSM results lying in the gray zone [9]. This would be an even more serious problem in obviously obese subjects, as the LSM is higher among those with a body mass index (BMI) above 30 kg/m in the same fibrosis stage [10]. On the other hand, the NAFLD fibrosis score (NFS) is the beststudied serum-based combined clinical algorithm; it was recommended in the latest American practice guidelines for NAFLD [11]. All these observations have raised the interest in combining these two well-studied noninvasive parameters. On the other hand, magnetic resonance elastography (MRE) is probably even more accurate than LSM and NFS [12]. Nonetheless, MRE is not as widely available as these two tools. Recently, Chan et al. [13] evaluated the diagnostic performance a novel two-step approach combining NFS and LSM. The beauty of this study was the robust methodology of including two independent groups of patients as the training and validation cohort, respectively. The detailed comparison of the performance of various approaches, be it either parameter alone or combining two parameters in different fashions, established this novel twostep approach as the best among the five to avoid liver biopsy. Similar approaches have been proposed in patients with chronic hepatitis B [14, 15]; this was the first time in NALFD patients. The unresolved questions remaining include the suboptimal performance of NFS in Asian subjects because of the different BMI cutoffs for obesity [16]. This was echoed by the relatively low sensitivity (40 %) of NFS to predict advanced fibrosis in Chan’s study. Investigators should pay special attention when applying any parameters derived from the west to Asian patients, such that different cutoffs or even different algorithms should be considered. It would be helpful if another serum parameter with better performance could be found. Cytokeratin-18 (CK18) fragments have been investigated extensively as novel biomarkers for G. L.-H. Wong H. L.-Y. Chan Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong

Chronic hepatitis B is the leading cause of hepatocellular carcinoma (HCC) in Asia. Despite liver resection or local ablation therapy, up to 70 % of patients will have HCC recurrence. While early HCC recurrence within 2 years of index treatment is mainly associated with tumor characteristics such as vascular invasion and tumor number, late recurrence arises due to field effect and is associated with high hepatitis B virus DNA level and hepatic necroinflammation. Although current data suggest that antiviral therapy can reduce the risk of cirrhosis and incident HCC, its role in preventing HCC recurrence after curative treatment remains controversial. In recent years, knowledge on the signaling pathways of HCC has led to exciting development in targeted therapy, with sorafenib being the first to be registered for the treatment of advanced HCC. Further studies are needed to clarify the role of targeted therapy in the adjuvant setting to prevent HCC recurrence.

Background Little is known of the prevalence of hepatitis B virus (HBV) infection and its effect on choice of therapy and disease course in patients with inflammatory bowel disease (IBD). We assessed the prevalence of HBV in Hong Kong as well as determinants of altered transaminases, effects of HBV infection on therapeutic strategy and clinical course in IBD. Methods In this retrospective cohort, hepatitis B surface antigen (HBsAg), liver function tests, and IBD disease characteristics were recorded. Logistic regression was used to identify factors associated with altered transaminases. Results Four hundred six IBD patients were recruited. HBV infection was found in 5.7 % patients in Hong Kong. The use of steroids (OR, 2.52; p = 0.010) and a previous history of surgery (OR 2.33; p = 0.026) were associated with altered transaminases in IBD. There was no significant difference in disease control and use of IBD medication between HBsAg-positive and HBsAg-negative IBD patients. Conclusion The prevalence of HBV among patients with IBD in Hong Kong (5.7 %) is similar to that of general population (~7 %). There was no difference in disease control and use of IBD medication between subjects with or without HBV.

South Asian immigrants living in the United Kingdom and Canada have been found to have lower rates of cancers of all types compared with the native born population and most other immigrant groups. Cancer among Asian Indian/Pakistani people in the United States has been studied very little. Incidence rates for all cancers combined and site-specific rates for major cancers were estimated for Asian Indians/Pakistani population using incidence data from the U.S. National Cancer Institutes SEER database and population data from the U.S. Census Bureau. Site-specific survival was compared for major cancer sites between Asian Indians/Pakistanis and Caucasians using Cox proportional hazards models. Cancer rates for Asian Indian/Pakistani males and females were considerably lower than for White Americans with standardized incidence ratios (SIRs) of 0.46 (95% CI = 0.44, 0.48), and 0.55 (95% CI = 0.53, 0.58) respectively. Site-specific rates were lower for both genders for most sites with particularly low rates observed for lung, colorectal, female breast, and prostate cancer. Among common cancers sites, survival was generally better among Asian Indians/Pakistanis than Caucasians with the notable exception of breast cancer for which Caucasians had slightly better survival. The finding that Asian Indians/Pakistanis in the United States have relatively low incidence rates for most major cancers is consistent with studies from other countries. Whether the low incidence of cancer and above average cancer survival for this group is related to their well-above average socioeconomic status or cultural and behavioral factors is a topic for further research.