Economic Analyses to Inform and Support Health Policy for Chronic Hepatitis B Treatment Abstract Purpose of Review Summarize insights into the economic impact of global hepatitis B treatment policies. Recent Findings With the highly effective antiviral treatment, entecavir and recently tenofovir, coming off patent, hepatitis B treatment is now very inexpensive and may save costs in the long run. In the USA alone, dramatic increases in screening and treatment would prevent between 80 and 100 thousand cases of cirrhosis, 50 and 60 thousand cases of liver cancer, and 80 to 100 thousand HBV-related deaths over the next 50 years. Summary Cost-effectiveness analyses can provide information in the form of what a proper course of action will cost, and what the benefits will be in terms of health impact. Since the sharp reduction in antiviral drug pricing, the focus should be on treating patients with generic antivirals to ensure that the chronic hepatitis B care and treatment efforts are highly cost-effective and even cost-saving.

Global Epidemiology of Drug-Induced Liver Injury (DILI) Abstract Purpose of Review Drug-induced liver injury (DILI) is not an uncommon liver disease in many parts of the world. DILI is one of the most common causes of acute liver failure in most countries. The current review summarizes the global epidemiology of DILI. Recent Findings The number need to harm in terms of DILI due to amoxicillin-clavulanate was approximately 1 out 2300, but was higher for azathioprine (1 out of 133) and infliximab (1 out of 148). A retrospective Chinese study showed the highest rate of DILI in hospitalized patients with an incidence of approximately 24 patients per 100,000 annually with a more favorable prognosis in the DILI cohort than previously reported from Europe, the USA, and Asia. Summary Although large DILI registries from Europe and the USA have collected much data, more prospective studies with continual enrollment are needed particularly as new therapies such as immune modulatory and oncological medications with longer half-lives and latencies come to market.

Strategies for Global Elimination of Chronic HBV Infection: 2019 Update Abstract Purpose of Review With just over a decade to go before the WHO 2030 hepatitis elimination targets, this review takes a global perspective at the major challenges standing in the way of hepatitis B virus (HBV) elimination and discusses potential innovative solutions on the horizon for use in high burden settings. Recent Findings Universal HBV infant vaccination has been an incredible success. However, in order to reach the elimination targets, efforts now need to urgently focus on scaling up HBV prevention of mother-to-child (PMTCT) interventions, particularly in sub-Saharan Africa and increasing population level testing and treatment. Summary Innovative outreach strategies, simplified diagnostics and novel biomarkers and integration of systems are promising solutions to allow HBV elimination to be reached in an effective and affordable way. This should go alongside careful financing, policy planning and establishment of strong surveillance systems.

The Role of Traditional Chinese Medicines (TCM) and Other Complementary and Alternative Medicines (CAM) in the Management of Chronic Hepatitis B Abstract Purpose of Review To provide a review and update of complementary and alternative medicine (CAM) approaches to the management of chronic hepatitis B, with particular emphasis upon traditional Chinese medicines (TCM). Recent Findings The major findings are as follows: (1) TCMs were better than interferons [IFN] in lowering serum HBeAg and normalizing serum ALT, and equivalent to IFN in clearing serum HBV DNA; (2) TCMs were equivalent to lamivudine [LAM] in lowering serum HBeAg, normalizing serum ALT, and clearing serum HBV DNA; (3) TCMs along with IFN or LAM significantly lowered serum HBeAg and improved the clearance of serum HBV DNA and the normalization of serum ALT, compared with IFN or LAM alone; (4) no serious adverse reactions of TCM were reported in all cited clinical trials. Although the composition of traditional medicines in the TCMs varied among RCTs, about 60% of the used herbs were homologous. Our major overarching conclusion was that TCMs seem effective as alternative remedies for patients with CHB. Other CAM approaches also are widely used, especially in east Asian countries, and there is limited evidence of benefit for some. Summary CHB continues to be a major health problem worldwide. Although nucleosides such as tenofovir and entecavir are highly effective at suppression of HBV replication, they are expensive and often beyond reach of patients, especially in resource-limited nations and regions. Many such patients will continue to rely upon CAM and TCM for management of their chronic hepatitis B infections. Additional carefully done, placebo-controlled prospective randomized trials of CAM and TCM in chronic hepatitis B should be performed.

Community-Based Strategies to Improve Screening, Diagnosis and Linkage to Care for Patients with Chronic Hepatitis B Abstract Purpose of Review Chronic hepatitis B (CHB) places 3.5% of the world population at risk of dying from liver failure or liver cancer. Effective antiviral therapies can change disease outcomes, provided that CHB screening and linkage to care can be delivered at population level, to reach the vast numbers of undiagnosed people. We therefore reviewed the experience of community-based CHB screening programs reported in the English literature since 2014. Recent Findings Twenty papers met eligibility criteria and only one originated from a low-income country. The two randomised studies found that culturally tailored hepatitis education increased hepatitis testing. Successful linkage to care was facilitated by partnerships with community-based organisations and the use of bilingual patient navigators. Point of care testing and chain referral sampling were successfully tested in two programs. Summary These studies demonstrated that community-based interventions can screen large numbers of people and could deliver the population-level outcomes required to meet the WHO targets of hepatitis B elimination.

Regional and Racial Differences in Drug-Induced Liver Injury Abstract Purpose of Review To summarize the growing epidemiologic and genetic data that suggest racial and regional differences in drug-induced liver injury (DILI). Recent Findings Several registries and population-based studies report incidence data across continents from 2 to 24 per 100,000 with China reporting the highest incidence estimate. The agents causing DILI vary by race and region as well. Hepatotoxicity from herbal and dietary supplement is on the rise globally with China reporting the highest levels. Genome-wide association studies are beginning to shed light on racial genetic and HLA variants which may determine the risk of DILI. Summary DILI risk and outcome vary by race and region due to a combination of epidemiologic and genetic factors. The rise and maturation of DILI registries worldwide are beginning to allow important discoveries in how we should consider the diagnosis of DILI by region and race.

Management of Virologic Failure in Patients with Chronic Hepatitis B Treated with Nucleos(t)ide Analogues Abstract Purpose of the Review Poorly controlled hepatitis B increases the risk for liver-related morbidity. Although there are now six approved nucleos(t)ide analogues (NA) for the treatment of chronic hepatitis B (CHB), drug resistance and thus virologic breakthrough still exist. This review outlines a systematic approach to the management of virologic failure in patients with CHB treated with NAs. Recent Findings Current NAs can be divided into older generation and newer generation agents, with newer generation agents associated with lower rates of virologic breakthrough. Both tenofovir dipovoxil fumarate (TDF) and tenofovir alafenamide (TAF) are equally as effective in addressing virologic breakthrough while on all other NAs. Entecavir is an effective treatment option for NA naïve patients only, with high rates of resistance to entecavir in those exposed to older NAs. Summary The management of virologic breakthroughs should focus on identifying risk factors for future drug resistance and escalation to appropriate newer generation drug options to avoid long-term liver-related morbidity.

Bile Duct Injury Due to Drug-Induced Liver Injury Abstract Purpose of Review Drug-induced liver injury (DILI) can present with a variable clinical and pathological phenotype and can be classified using liver enzymes as hepatocellular, cholestatic, or a mixed pattern. The cholestatic pattern has been considered amongst the spectrum of direct liver damage at the microscopic level, but recently, bile duct injury, as a manifestation of DILI, has emerged as a distinct entity, and this review examines several examples of biliary tract abnormalities due to DILI from a clinical, radiologic, and pathologic perspective. Recent Findings Case series and reports have emerged over the last few years of drugs causing cholangiographic changes or direct injury to the intra- and extra-hepatic biliary tree, such as ketamine and several chemotherapy agents. The DILI Network (DILIN) in the USA has published their experience of cases with vanishing bile duct syndrome on histology and sclerosing cholangitis-like changes seen on cholangiography. The pathogenesis of these changes is unclear but it appears that this type of injury is more severe and more likely to lead to a chronic injury with increased mortality than other cases of DILI. Summary Bile duct injury due to DILI is an increasingly recognized entity and imaging of the biliary tree in conjunction with liver biopsy should be considered in patients with severe cholestatic DILI.

Epidemiology, Diagnosis, and Management of Bone Disease in Patients with Chronic HBV Infection Abstract Purpose of Review Chronic hepatitis B (CHB) and treatment may be associated with increased risk of osteopenia/osteoporosis. Here, we review the prevalence of osteopenia/osteoporosis among patients with CHB and the effect of antiviral therapy on bone density. We also highlight screening and management strategies for bone disease among patients with CHB. Recent Findings While there are concerns with first-line antiviral therapy such as tenofovir disoproxil fumarate in the development of osteopenia/osteoporosis, the available data remain rather unclear. However, with the development of tenofovir alafenamide, these concerns may be mitigated. At present, EASL recommends dual-energy X-ray absorption (DEXA) scans for patients with osteoporotic risk factors, with a repeat DEXA scan based upon baseline findings. Summary Patients with CHB have higher incidence and prevalence of osteopenia/osteoporosis compared with patients without CHB. Further studies are needed to understand the impact of antiviral therapy on bone therapy, and more CHB specific recommendations are needed for bone health management.

The Role of Liver Biopsy in Drug-Induced Liver Injury Abstract Purpose of Review This review presents the current understanding of the role played by liver biopsy in the diagnosis and management of drug-induced liver injury (DILI). Recent Findings While liver biopsy remains an optional procedure in the evaluation of DILI, it has the potential to provide detailed information about the state of the liver. Recent histological surveys of DILI provide a framework for categorizing the patterns of injury that may be seen. Pattern information can be used to distinguish DILI from other potential causes of injury, both other acute injuries as well as pre-existing injury. The pattern of injury is related to differential diagnosis and in some cases can suggest a mechanism of injury. The character and severity of the injury could potentially be used in clinical decision-making. Examples of the use of liver biopsy in the context of DILI encountered in clinical trials are provided which highlight these points. Summary Liver biopsy may be a useful tool in DILI evaluation, particularly in complex clinical situations and clinical trials with experimental therapies.