The research combined a population-wide serosurvey with targeted testing among selected immigrant communities. Investigators screened the nationally representative sample for hepatitis B surface antibodies, or HBsAb, and analyzed results by age, sex, ethnicity, socioeconomic status and residential setting. In the separate immigrant sample, they assessed hepatitis B surface antigen, or HBsAg, and screened HBsAg-positive samples for hepatitis D virus, or HDV. The two components therefore measured different outcomes in different populations and were not equivalent to a uniform national survey of HBsAg and HDV prevalence.

HBsAb seropositivity was 49.2% among people born in or after 1992, when universal hepatitis B vaccination was introduced nationally, compared with 36.0% among those born before that year, a difference reported as p < 0.0001. The results also showed lower antibody positivity among people with lower socioeconomic status and among those living in peripheral areas. For the comparisons reported by the researchers, the odds ratio was 1.51 for high versus low socioeconomic status, with a 95% confidence interval of 1.29–1.78, and 1.61 for central versus peripheral residency, with a 95% confidence interval of 1.23–2.09. Ethnic patterns also varied with age: Jewish and other minority populations had higher rates in younger cohorts, whereas the Arab population had higher rates among older participants. These were cross-sectional associations, and the reported data do not establish that vaccination, ethnicity, socioeconomic conditions or residence caused the observed differences.

Among the selected immigrant samples, HBsAg prevalence was 9% among people from Ethiopia and 9% among people from Ukraine. Among HBsAg-positive carriers from Africa, 8.2% also tested positive for HDV. The reported estimate applies to the African carrier group represented in the study and should not be interpreted as a separate prevalence value for every African population. Moreover, because the immigrant component included selected populations rather than a nationally representative sample covering all origins, the study does not establish a comprehensive prevalence of HBsAg or HDV among all immigrants in Israel.

The findings show that the national vaccination program coincided with higher HBsAb seropositivity in the younger birth cohort, while important seropositivity gaps remained across demographic and social groups. The targeted immigrant results further document HBsAg prevalence in Ethiopian and Ukrainian samples and HDV coinfection among African HBsAg-positive carriers. The investigators concluded that screening strategies should be considered, particularly for high-risk immigrants and specified immigrant populations, while the study’s cross-sectional design and selected sampling limit conclusions about causes, changes over time and population-wide prevalence.

Subject of Research: Hepatitis B seroprevalence and hepatitis D coinfection across Israeli demographic and immigrant populations

Article Title: National HBsAb serosurvey and HBsAg/Hepatitis D coinfection prevalence across sociodemographic and immigrant populations in Israel

Article References: Yael, G., Keren, A., Lital, K.-B., Shoshana, A. S., Orit, P., Orna, M., & Ravit, B. (2026). National HBsAb serosurvey and HBsAg/Hepatitis D coinfection prevalence across sociodemographic and immigrant populations in Israel. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14403-2

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14403-2

Keywords: hepatitis B, hepatitis D, HBsAb, HBsAg, serosurvey, viral infections, immigrant health, Israel, socioeconomic disparities, national vaccination, National, Hepatitis

The policy sequence examined in the study began with a change from the Centers for Disease Control and Prevention’s prior recommendation of universal hepatitis B vaccination at birth. In December 2025, the Advisory Committee on Immunization Practices recommended deferred vaccination for infants whose mothers did not have hepatitis B until the infants were at least two months old. In January 2026, the CDC switched to recommending a shared clinical decision-making approach for those infants.

The source said the recommendations had been challenged by professional medical societies and public health agencies, but their clinical effects were unclear. The study, published in Annals of Internal Medicine , assessed the projected effects of these strategies rather than measuring outcomes under the new policies. Researchers from Mass General Brigham used a Markov cohort state-transition model to follow a synthetic population across health states over time.

The model was built with published epidemiological data and validated by comparing its projections with real-world CDC estimates of pediatric hepatitis B infections. It followed 3.6 million people, representing one year of births in the United States, through the first 20 years of life. Vaccination was recommended in every scenario for infants whose mothers were known to be hepatitis B positive.

The shared clinical decision-making scenario assumed that 50% of infants whose mothers were hepatitis B negative would be vaccinated at two months of age or later. The delayed-vaccination scenario assessed vaccination beginning at two months or later, while the comparison strategy was universal vaccination at birth. Under universal birth vaccination, the model projected that 255 people in the birth cohort would have chronic hepatitis B infection by age 20.

The count rose to 303 under delayed vaccination and 467 under shared clinical decision-making. These differences corresponded to projected increases of 48 and 212 chronic infections, or approximately 19% and 83%, respectively, relative to vaccination at birth. The model also projected a large difference in susceptibility at age 20: approximately 232,000 people would remain susceptible under universal birth vaccination, compared with about 474,000 under delayed vaccination and 1.8 million under shared clinical decision-making.

The study therefore projected both more chronic infections and a larger pool of susceptible young adults under each alternative to vaccination at birth. The authors emphasized the clinical importance of the projected increase in adult susceptibility. They said hepatitis B infections acquired in adulthood have a higher likelihood of leading to life-threatening conditions, including acute liver failure, and noted that hepatitis B is also a common cause of liver cancer.

Amir Mohareb, the study’s corresponding author, said in the research news release that even a small increase in childhood infections could have large clinical, public health and economic effects. Because the analysis is a model projection based on published data and specified vaccination assumptions, it does not establish how many infections will actually occur or how the recommendations will affect individual families. Its findings remain conditional on the model’s assumptions, including the 50% vaccination rate assigned to the shared clinical decision-making scenario and the accuracy of the input epidemiological data.

Subject of Research: Modeled effects of US infant hepatitis B vaccination schedule changes on chronic infections and susceptibility through age 20.

Article Title: Changes to hepatitis B immunization schedule would increase infections, model predicts

Article References: Changes to hepatitis B immunization schedule would increase infections, model predicts. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: hepatitis B, HBV, infant vaccination, immunization schedule, cohort model, chronic infection, shared clinical decision-making, adult susceptibility, US births, public health, Changes, hepatitis

The study evaluated proposed changes to the U.S. childhood hepatitis B vaccination schedule that would affect infants born to women without hepatitis B infection. The baseline strategy was vaccination of every newborn. One alternative was deferred vaccination at two months for infants whose mothers did not have hepatitis B infection, consistent with an Advisory Committee on Immunization Practices recommendation from December 2025. The second alternative used shared decision-making for vaccination at two months among the same group, reflecting a Centers for Disease Control and Prevention proposal from January 2026.

Researchers from Massachusetts General Hospital and Harvard Medical School developed a Markov state-transition model to project the long-term consequences of the three strategies for one birth cohort of 3.6 million infants. The model compared universal vaccination at birth with vaccination deferred to two months and with a shared-decision-making approach at two months. It was not a clinical trial in which infants were assigned to vaccination schedules, and the reported results do not describe outcomes observed under either proposed policy.

The model used chronic hepatitis B infection acquired by age 20 as one principal outcome. It also assessed how many children would enter adulthood vulnerable to hepatitis B infection. Universal birth-dose vaccination served as the reference against which the two proposed alternatives were compared. The release did not provide uncertainty intervals for the reported percentage changes, so the results are best interpreted as projections for the specified strategies and modeled birth cohort rather than precise forecasts of what would occur nationwide.

Deferring the first vaccine dose until age two months for infants born to women without hepatitis B infection was projected to produce a 19% increase in chronic hepatitis B infections acquired by age 20 relative to universal newborn vaccination. This estimate applies to the cohort and policy specification evaluated in the model. The research summary did not report the absolute number of additional infections associated with the projected increase, so the percentage cannot be converted into a reported count of additional cases from the available evidence.

The shared-decision-making strategy yielded the largest projected difference from the birth-vaccination baseline. Under that approach, the model estimated an 83% increase in chronic hepatitis B infections acquired by age 20 compared with vaccinating all newborns. The analysis also projected that more than half of children entering adulthood would be vulnerable to hepatitis B infection. That estimate applies to the shared-decision scenario as modeled; it does not indicate that a majority of U.S. adults are currently vulnerable or that an implemented policy has already produced this outcome.

The contrast between the two alternatives is the central difference in the model results. Deferring vaccination to two months for the specified group was associated with a smaller projected rise in chronic infections, while making the same two-month vaccination contingent on shared decision-making was associated with a substantially larger increase. The release did not report the proportion of parents expected to accept or decline vaccination under the shared-decision strategy, nor did it provide the assumptions used to represent that decision process.

Within the three strategies examined, universal hepatitis B vaccination at birth produced the lowest projected number of chronic infections and the lowest projected adult vulnerability. The authors therefore concluded that universal birth-dose vaccination remained the most effective of the compared strategies for preventing childhood infections and reducing future vulnerability to the virus. This conclusion concerns the model’s comparison of vaccination strategies; the investigators did not directly observe policy outcomes or measure vaccine effectiveness through a prospective or randomized intervention.

The analysis is bounded by several features of the supplied study description. It covered one birth cohort of 3.6 million infants and focused on long-term outcomes through age 20 under specified vaccination policies. The research was a model projection rather than an evaluation of completed vaccination programs, and the news release did not quantify uncertainty around the 19% and 83% percentage changes. It also did not report the model’s full parameter set or provide results for other birth cohorts, regions or schedule scenarios.

The publication examines a specific set of federal policy changes to childhood immunization in the United States. Its scope was the projected effect of changing when or how the first hepatitis B vaccine dose is administered for infants born to women without hepatitis B infection, with chronic infection by age 20 and vulnerability upon entering adulthood as the reported outcomes. The findings quantify modeled differences among the strategies, but they do not establish the causal effects of an implemented policy because all three schedules were evaluated within a model rather than through direct observation of children assigned to each schedule.

The clearest supported result is that the model found a protective advantage for vaccination at birth within the strategies compared. Delaying vaccination to two months was projected to raise chronic infections acquired by age 20 by 19%, while shared decision-making at two months was projected to raise the same measure by 83%. These figures should not be confused with observed national infection trends, completed policy outcomes or clinical recommendations beyond the study. The peer-reviewed modeling article was scheduled to appear in Annals of Internal Medicine on October 20, 2026, following the American College of Physicians news release dated October 19, 2026.

Subject of Research: Modeled effects of proposed U.S. childhood hepatitis B vaccination policy changes on chronic infections by age 20

Article Title: Proposed changes to hepatitis B vaccination schedule could significantly increase infections, model suggests

Article References: Proposed changes to hepatitis B vaccination schedule could significantly increase infections, model suggests. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: hepatitis B, childhood vaccination, birth-dose vaccination, chronic infection, US immunization policy, shared decision-making, Markov model, infectious disease, public health, Proposed, changes, hepatitis

Hepatitis B remains one of the world’s most consequential viral infections. The virus chronically infects a substantial share of the global population, and long-standing infection can progress to cirrhosis and liver cancer. The burden falls disproportionately on low-resource settings, precisely where sophisticated diagnostic infrastructure is scarcest. Quantitative PCR, the molecular gold standard, demands expensive thermocyclers, fluorescence optics, trained personnel and reliable supply chains, which confines it to urban reference laboratories. Serological rapid tests are cheap and widely deployed, but they detect antibodies or viral antigens rather than viral DNA, and their performance can falter early in infection or in immunocompromised patients. The gap between what is technically possible and what is practically available has long motivated the search for alternative amplification chemistries.

Polymerase spiral reaction belongs to a family of isothermal amplification methods that dispense with the repeated heating and cooling cycles of conventional PCR. Instead of a pair of standard primers, PSR uses a specially designed set of four primers that recognize six distinct regions on the target sequence. The primers carry self-complementary tails, so the amplicons they generate fold into structures that present single-stranded loops resembling the original target. A strand-displacing polymerase then primes new synthesis from these loops, setting off a self-sustaining spiral of extension and displacement. Because the reaction never needs to melt double-stranded DNA thermally, it runs at a single fixed temperature, in this case 63 degrees Celsius, achievable with a simple water bath or heating block.

The research team, led by Prerana Sharan and Praveen Rai of Nitte University Centre for Science Education and Research, with collaborators at KS Hegde Medical Academy, AJ Institute of Medical Sciences and the National Institute of Biologicals, targeted a specific region of the HBV S gene, which encodes the viral surface antigen. Primer design is the critical step in any isothermal assay: the primers must bind tightly enough to initiate amplification but not so promiscuously that they generate signal from unrelated sequences. After systematic optimization of reaction temperature, duration, magnesium concentration and primer amounts, the assay settled on 63 degrees for 60 minutes as the condition that maximized amplification efficiency while preserving specificity.

The visual readout relies on hydroxy naphthol blue, a metallochromic dye that changes hue depending on the amount of free magnesium in the reaction mixture. As the polymerase incorporates nucleotides, it consumes magnesium ions, and the accumulating amplicons shift the dye from violet to blue. An operator can therefore distinguish positive from negative reactions by naked eye within the hour, without fluorescence detectors, gel electrophoresis or any optical instrumentation. This dye-based approach has been used with other isothermal methods, but its combination with PSR for HBV is what the new study demonstrates.

Analytical performance was striking. Serial dilutions of quantified HBV plasmid DNA established a detection limit of 5.04 copies per reaction, a figure that places the assay among the most sensitive isothermal methods reported for this virus. Specificity testing showed no cross-reactivity with other hepatitis-causing viruses, including hepatitis C virus, or with a panel of unrelated pathogens, indicating that the primer set discriminates reliably between HBV and genetically distinct organisms that might co-circulate in the same patient.

Clinical evaluation followed. The team tested 85 samples, including 45 previously screened as HBV-positive by serological assay. Against the reference results, the PSR assay achieved 100 percent sensitivity and 100 percent specificity, a perfect concordance rate in the evaluated set. The authors note that the assay outperformed conventional PCR in the clinical samples they examined, although they acknowledge that the sample size, while adequate for a proof of concept, will need expansion in larger multi-center trials before the assay can be deployed at scale.

The study was approved by the Institutional Ethics Committee of Nitte Deemed to be University and used anonymized residual clinical samples, with the requirement for informed consent waived. The work was supported by a Faculty Research Grant from Nitte Deemed to be University. The article is published open access under a Creative Commons Attribution 4.0 license, and the authors declare no competing interests.

The implications extend beyond hepatitis B. The same PSR chemistry, coupled with HNB or related dyes, could in principle be adapted to other viral targets by redesigning the primer set, offering a modular platform for point-of-care molecular diagnosis. The authors frame their assay as a tool for early surveillance and detection, particularly aimed at healthcare in poor-resource settings, where the combination of isothermal amplification and dye-based visual readout eliminates the need for complex instruments. Whether the assay can maintain its analytical performance outside the controlled environment of a research laboratory, and whether it can be integrated into routine screening programs, are questions that larger validation studies will need to address.

For now, the study adds to a growing body of work demonstrating that molecular diagnosis need not be confined to centralized facilities. A reaction that runs at a single temperature, completes in an hour, and announces its result through a color change visible to the naked eye represents a meaningful step toward diagnostics that meet the virus where it actually circulates. As the authors conclude, the HBV-PSR assay could potentially serve as a point-of-care diagnostic tool for HBV detection, with the goal of early surveillance and detection focused on healthcare in resource-poor settings.

Subject of Research: Virology

Article Title: Colorimetric polymerase spiral reaction (PSR) assay for the rapid detection of hepatitis B virus

Article References: Sharan, P., Bhandary, R., Rao, C., Maiti, B., Kumar, B. K., Kumar, A., & Rai, P. (2026). Colorimetric polymerase spiral reaction (PSR) assay for the rapid detection of hepatitis B virus. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-026-14058-8

Image Credits: AI Generated

DOI: 10.1007/s00253-026-14058-8

Keywords: Colorimetric, polymerase, spiral, reaction, assay, rapid, detection, hepatitis, virus, scientific research

The study drew on monthly and annual reported case counts from China’s Public Health Science Data Center, covering 192 consecutive monthly observations for each virus from January 2005 to December 2020. Reported incidence was calculated as cases per 100,000 permanent residents, using year-end population figures from the Hainan Provincial Bureau of Statistics as the denominator. To place the provincial data in context, the team also extracted national Global Burden of Disease (GBD) estimates for China spanning 1990 to 2023, and they obtained annual tourist visit statistics from the provincial tourism department. No missing or duplicate observations were identified, and no study years were excluded, giving the analysis a complete and unbroken record.

Joinpoint regression, a technique that identifies inflection points in a time series and estimates the annual percent change (APC) within each segment, revealed a distinctly phased pattern for reported hepatitis B incidence in Hainan. Rates fell from 2005 to 2008 with an APC of −9.10 percent per year, rose from 2008 to 2018 with an APC of +10.50 percent per year, and then showed a non-significant decline through 2020. Across the full sixteen years, the average annual percent change (AAPC) was +3.37 percent, a statistically significant overall increase. Reported hepatitis C followed a different course: it climbed continuously from 2005 to 2015 at a striking +32.10 percent per year, then declined at −10.90 percent per year through 2020, yielding an overall AAPC of +14.54 percent. By contrast, the national GBD estimates showed overall AAPCs of −0.54 percent for hepatitis B and −1.52 percent for hepatitis C, both modestly downward over their respective periods.

The divergence between provincial reported data and national modeled estimates is a central finding. The authors caution that the two data sources differ in definition and origin, so national GBD trends serve only as contextual references. Still, the mid-period rise in reported hepatitis B in Hainan is unlikely to reflect a simple failure of vaccination strategy. China added hepatitis B vaccination to its childhood immunization program decades ago, and studies from Guangzhou and Xiamen have documented declining reported incidence in those cities. The Hainan increase may instead reflect expanded screening, greater detection of previously acquired chronic infections, repeated healthcare encounters, rising healthcare accessibility, and changes in reporting-system sensitivity, layered on top of genuine transmission dynamics and increasing vaccine-derived protection in younger birth cohorts. China continues to carry a large reservoir of chronic hepatitis B infection, and insufficient diagnosis, treatment, and follow-up remain major barriers to elimination.

For hepatitis C, the pre-2015 surge in reported incidence plausibly mirrors improvements in testing capacity, strengthening of the reporting infrastructure, and increased screening that uncovered previously undiagnosed infections. The post-2015 decline coincided with broader gains in blood safety, awareness, screening, and access to antiviral therapy, including the transformative arrival of direct-acting antivirals (DAAs), which can cure chronic hepatitis C infection in most treated patients. Yet the authors note that Hainan-specific information on testing and treatment coverage was unavailable, so the analysis cannot determine whether these factors caused the observed decline. A large pool of undiagnosed infections may continue to limit progress, since DAAs alone cannot reach patients who are never screened or linked to care.

Seasonality, often a signature of environmentally driven pathogens, was conspicuously absent for both viruses. The team applied seasonal-trend decomposition using Loess (STL), an additive method that splits each monthly series into trend, seasonal, and remainder components with a twelve-month seasonal period. Kruskal–Wallis tests comparing the distributions of the STL seasonal components across calendar months found no statistically significant differences for hepatitis B (H = 11.10, P = 0.435) or hepatitis C (H = 2.81, P = 0.993). Descriptive seasonality indices were highest in July for hepatitis B (107.8) and April for hepatitis C (107.4), and lowest in February for both (78.3 and 73.9, respectively). The February trough may relate to reduced healthcare seeking and delayed testing during the Spring Festival holiday, but the authors stress that these fluctuations likely reflect reporting variation rather than seasonal transmission, and that long-term trends and population-structure changes carry greater public health relevance than isolated monthly peaks.

To project future trajectories, the researchers fitted seasonal autoregressive integrated moving average (SARIMA) models to the monthly series. For hepatitis B, the selected model was SARIMA (0,1,2) × (2,1,0) with a twelve-month seasonal cycle, which had the lowest Akaike information criterion among candidates and passed the Ljung–Box residual autocorrelation test at lag 12 (Q = 10.771, P = 0.549). For hepatitis C, SARIMA (1,1,1) × (0,0,1) was chosen because an alternative with slightly lower information criteria retained significant residual autocorrelation; the selected model showed acceptable diagnostics at lag 24 (Q = 31.162, P = 0.074). Forecasting to 2030, the annualized projected reported hepatitis B incidence was 12.00 per 100,000 population, with a 95 percent prediction interval spanning roughly 0.00 to 121.20, numerically close to the study-defined reference value of 12.20. The hepatitis C projection was 22.54 per 100,000 (approximately 0.00 to 39.10), about 6.4 times the study-defined reference value of 3.55. The reference values were defined as 10 percent of the corresponding 2015 reported incidence rates, echoing the WHO framework of a 90 percent reduction in new infections by 2030, but the authors insist they are not equivalent to WHO elimination targets.

The wide prediction intervals, generated from 10,000 simulated forecast paths, signal substantial long-term uncertainty, and the authors repeatedly warn that the projections are conditional extrapolations of historical reporting patterns. A declining trend, they note, does not necessarily imply proximity to elimination. Hepatitis B control depends on sustained immunization coverage, prevention of mother-to-child transmission, adult diagnosis and treatment, and management of chronic infection, whereas hepatitis C elimination hinges on active screening, rapid linkage to treatment after diagnosis, and improved treatment coverage. Insufficient screening, incomplete linkage to care, declining treatment uptake, and ongoing transmission in high-risk populations may all weaken control efforts even in the DAA era.

Sensitivity analyses highlighted the disruptive fingerprint of the COVID-19 pandemic year. When Joinpoint models were refitted excluding 2020, the overall AAPC rose from 3.37 to 4.96 percent per year for hepatitis B and from 14.54 to 16.43 percent per year for hepatitis C, indicating that the 2020 observations deviated from prior reporting patterns and pulled the long-term trend estimates downward. Out-of-sample SARIMA forecasts built on 2005–2019 data predicted a mean monthly reported hepatitis B incidence of 15.11 per 100,000 for 2020, but the observed value was 10.98, some 27.3 percent lower; for hepatitis C, the forecast of 1.92 exceeded the observed 1.74 by 9.5 percent. Reduced healthcare seeking, testing, and reporting during pandemic-control measures, consistent with findings from China, Spain, and Italy, likely explain these shortfalls rather than any sudden improvement in prevention.

Finally, the study explored ecological associations between annual tourist visits, which grew from roughly 17 million in 2005 to about 83 million in 2019 before falling to approximately 56 million in 2020, and reported hepatitis incidence. In raw annual analyses, tourist visits correlated strongly with both reported hepatitis B (r = 0.871) and hepatitis C (r = 0.879), both P < 0.001, and the associations persisted after excluding 2020. However, because both series shared pronounced long-term trends, the team repeated the correlations on first-differenced and linearly detrended data. Only the hepatitis B association survived (r = 0.567 after differencing, P = 0.028; r = 0.691 after detrending, P = 0.003), while the hepatitis C association vanished (r = 0.070, P = 0.804 after differencing). The authors interpret this cautiously: tourism volume may reflect concurrent changes in population mobility, healthcare use, screening activity, socioeconomic development, and reporting capacity rather than any direct causal effect on transmission. The analyses were aggregated and exploratory, lacking individual-level data on age, sex, vaccination status, transmission route, testing, and treatment. The authors conclude that Hainan should maintain hepatitis B immunization and screening while prioritizing hepatitis C screening, diagnosis, and linkage to treatment, supported by continued surveillance among mobile and key populations as the province’s free trade port development accelerates population mobility.

Subject of Research: Infectious Disease Epidemiology

Article Title: Trends and forecasting of reported hepatitis B and hepatitis C incidence in Hainan Province, China, 2005–2020

Article References: Wang, J., Li, S., Fu, C., Su, Y., Fu, H., Tian, Y., & Lan, C. (2026). Trends and forecasting of reported hepatitis B and hepatitis C incidence in Hainan Province, China, 2005–2020. Frontiers in Epidemiology, 6, Article 1899759. https://doi.org/10.3389/fepid.2026.1899759

Image Credits: AI Generated

DOI: 10.3389/fepid.2026.1899759

Keywords: hepatitis B, hepatitis C, Hainan Province, time-series analysis, SARIMA forecasting, viral hepatitis surveillance, China, Trends, forecasting, reported, hepatitis, incidence

The story began in February 2022, when the patient was admitted to a hospital with hoarseness and coughing up blood. Imaging and pathology confirmed left lung adenocarcinoma with brain metastases, classified as stage IV under the American Joint Committee on Cancer TNM staging system, eighth edition. His tumor biology was aggressive: immunohistochemistry revealed a Ki-67 proliferation index of 70 percent and a PD-L1 tumor proportion score of 90 percent, while genetic testing showed wild-type EGFR and ALK. Because his tumor expressed PD-L1 so strongly, he was enrolled in a randomized, double-blind, placebo-controlled trial testing an anti-TIGIT antibody alongside atezolizumab for advanced non-small cell lung cancer. On March 21, 2022, he completed one cycle of atezolizumab at 1,200 milligrams plus the anti-TIGIT antibody or placebo at 600 milligrams, both intravenously, without immediate complications.

Less than a month later, the trouble started. The patient developed fatigue, facial swelling, and a rash. Laboratory tests on April 18, 2022 revealed elevated liver enzymes, with alanine aminotransferase at 71.9 units per liter and aspartate aminotransferase at 193.1 units per liter, along with abnormal cardiac markers including cardiac troponin T at 0.036 nanograms per milliliter, creatine kinase-MB at 41.8, and myoglobin at 1,371 nanograms per milliliter. Doctors at the first hospital suspected immune-related myocarditis, hepatitis, and secondary adrenal insufficiency, stopped the immunotherapy, and started methylprednisolone at 60 milligrams twice daily, later escalating the dose. Follow-up was disrupted by the COVID-19 pandemic, and by late May the patient had worsening chest discomfort, severe facial and neck edema, and a widespread rash. Neck computed tomography showed tonsillitis and inflammation of the parotid and submandibular glands compressing the trachea enough to require intubation. His platelet count then crashed to 15 times 10 to the ninth per liter, and his liver function deteriorated further.

When the patient reached the team at Zhongshan Hospital, Fudan University, the physicians conducted a systematic re-evaluation of each suspected immune-related adverse event. Cardiac magnetic resonance imaging with enhancement revealed scattered patchy enhancement in the left ventricular lateral wall and linear delayed enhancement in the subepicardium of the inferoposterior wall, findings strongly suggestive of grade 3 checkpoint inhibitor myocarditis, with a left ventricular ejection fraction of 50 percent. Pulmonary embolism and worsening of pre-existing cardiovascular disease were ruled out. A liver biopsy showed mild sinusoidal congestion, subtle inflammatory infiltration, bile stasis, hepatocyte swelling, and focal necrosis, consistent with grade 2 immune-related hepatic injury in the absence of liver metastases, viral hepatitis, or autoimmune disease. A bone marrow biopsy demonstrated poor maturation of megakaryocytes without tumor invasion, supporting grade 4 immune-mediated thrombocytopenia. Finally, the combination of widespread muscle soreness, facial and periorbital swelling, elevated creatine kinase dominated by the skeletal muscle fraction, and impaired self-care pointed to grade 4 dermatomyositis, with the MDA5 antibody testing negative.

Treatment was aggressive and multidisciplinary. The patient received intravenous methylprednisolone at 160 milligrams daily for five days, together with intravenous immunoglobulin at 20 grams daily for seven days, plus hepatoprotective, gastric-protective, anti-infective, and nutritional support. Cardiac troponin stabilized and platelet counts rose significantly, but liver enzymes and bilirubin continued climbing, prompting the addition of tofacitinib, a Janus kinase inhibitor, at 5 milligrams per day starting June 11, 2022. Liver function and the rash gradually improved, allowing tapering of the methylprednisolone from June 19 onward. After discharge, steroids were tapered weekly, and tofacitinib was stopped when the oral dose reached 30 milligrams per day. Yet each attempt to withdraw immunosuppression backfired: at 10 milligrams of methylprednisolone, pruritic rashes reappeared on the right lower limb with rising creatine kinase-MB, requiring a five-day course of intravenous methylprednisolone at 40 milligrams. A second taper attempt triggered worsening rashes and elevations in troponin, creatine kinase, and creatine kinase-MB, and tofacitinib was reintroduced.

Because the dermatomyositis persisted and multiple organ systems remained involved, steroid withdrawal proved impossible. The team settled on a long-term maintenance regimen of low-dose methylprednisolone, 5 milligrams every other day, plus tofacitinib 5 milligrams twice daily. To date, the patient has improved markedly, with rashes substantially alleviated, normal liver function, and normalization of most cytokines and cardiac markers. In a striking twist, he has received no anti-tumor therapy since the adverse events began, yet his tumor remained stable for a long period, a phenomenon the authors note with interest, before follow-up chest computed tomography on December 13, 2024 showed localized recurrence.

The clinical course illustrates why checkpoint inhibitor myocarditis demands such vigilance. Although cardiac involvement is among the rarer immune-related adverse events, it carries a mortality rate of 25 to 50 percent, with rapid onset, atypical symptoms, and swift progression. Risk factors include combination checkpoint blockade, concurrent cardiotoxic cancer drugs, and pre-existing cardiovascular disease. High-dose corticosteroids are the cornerstone of treatment, and guidelines such as those from the National Comprehensive Cancer Network recommend permanent discontinuation of checkpoint inhibitors, electrocardiographic and echocardiographic monitoring, and pulsed methylprednisolone for three to five days in grade 3 cases, followed by tapering over four to six weeks. When patients resist steroid pulse therapy, guidelines suggest adding a chemotherapeutic or biological agent plus immunoglobulins, with antithymocyte globulin or alemtuzumab offering potential advantages. In this case, the combination of immunoglobulin and tofacitinib alongside steroids appeared to play a critical role in achieving disease control.

The hepatic and hematological complications add further lessons. Immune-related liver injury typically emerges six to fourteen weeks after starting checkpoint inhibitors, with an incidence around 8.4 percent in one cited cohort, and patients receiving dual immune therapy are more susceptible to hepatotoxicity. Steroid dosing for hepatitis is generally lower than for myocarditis, scaled to the grade of liver dysfunction, and the pathological basis, autoimmune cells attacking normal hepatocytes, mirrors that of cardiac injury. The authors also raise an unresolved question: when patients are already on high-dose steroids and immunoglobulins, should standard hepatoprotective drugs be continued? Current guidelines offer little guidance on this point. Immune thrombocytopenia, meanwhile, occurs in fewer than 1 percent of checkpoint inhibitor recipients, usually within the first twelve weeks, and remains a diagnosis of exclusion. Because thrombocytopenia is common in cancer patients, clinicians must systematically rule out infection, tumor progression, and drug effects before attributing it to immunotherapy, as the team did here through bone marrow biopsy and careful history-taking.

What makes this case scientifically valuable is its rarity and its implications for the next generation of immunotherapy. TIGIT, a co-inhibitory receptor expressed on T cells and natural killer cells that competes with the costimulatory molecule CD226 for the ligands CD155 and CD112, has shown synergistic anti-tumor effects with PD-1 and PD-L1 blockade in preclinical studies, and trials of tiragolumab combinations have generally reported acceptable safety profiles. Yet this patient experienced four simultaneous, severe immune-related adverse events after a single treatment cycle, underscoring that combining checkpoints acting on different pathways can amplify loss of immune tolerance in unpredictable ways. The authors emphasize that multisystemic immune-related adverse events tend to appear early and progress rapidly, that glucocorticoids remain the core therapy, and that severe cases may require intravenous immunoglobulin, plasma exchange, or additional immunomodulatory drugs such as tofacitinib. For oncologists deploying anti-TIGIT and anti-PD-L1 combinations in trials and clinics, the message is clear: early recognition, precise diagnosis across organ systems, and prompt multidisciplinary intervention can mean the difference between catastrophe and recovery.

Subject of Research: Multisystemic immune-related adverse events from anti-PD-L1 and anti-TIGIT combination immunotherapy in lung adenocarcinoma

Article Title: Management of multisystemic irAEs associated with atezolizumab/tiragolumab combination therapy in a patient with lung adenocarcinoma: case report and review

Article References: Zhang, S., Zhang, N., Lin, J., Zhao, L., Jin, H., Gao, D., Ji, Z., Liu, Q., Ai, L., & Yu, Y. (2025). Management of multisystemic irAEs associated with atezolizumab/tiragolumab combination therapy in a patient with lung adenocarcinoma: case report and review. Clinical Cancer Bulletin, 4(1), Article 6. https://doi.org/10.1007/s44272-025-00034-2

Image Credits: AI Generated

DOI: 10.1007/s44272-025-00034-2

Keywords: immune checkpoint inhibitors, atezolizumab, tiragolumab, TIGIT, PD-L1, myocarditis, immune-related adverse events, lung adenocarcinoma, dermatomyositis, thrombocytopenia, hepatitis, tofacitinib