Muniswamy, Jai Kumar Rajavoor

Portal hypertension is a central driver of morbidity and mortality in advanced chronic liver disease, yet its contribution to death is frequently underestimated owing to underreporting on death certificates. Population-level data on portal hypertension-related mortality trends and disparities in the United States remain limited. We conducted a retrospective, population-based mortality study using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death database, identifying deaths with International Statistical Classification of Diseases and Related Health Problems, 10th Revision code K76.6 listed in any cause-of-death field from 1999 to 2023. Crude and age-adjusted mortality rates per 100,000 population were calculated and stratified by sex, U.S. Census region, race/ethnicity, and urban–rural status (the latter restricted to 1999–2020 due to data availability). Temporal trends were assessed using Joinpoint regression, with annual percent change (APC) reported as the primary trend metric and 95% confidence intervals presented for all estimates. A total of 34,551 portal hypertension-related deaths were identified. Overall age-adjusted mortality rates declined sharply from 1999 to 2002 (APC − 12.85%), plateaued for more than a decade, and rose thereafter. Mortality increased significantly in women after 2009 (APC + 6.69%) and in men after 2013 (APC + 6.18%). Among racial and ethnic groups, Hispanic or Latino individuals consistently demonstrated the highest mortality burden throughout the study period, followed by White individuals, whereas Black or African American individuals exhibited comparatively lower but significantly rising rates from 2006 onward. White individuals demonstrated the steepest recent acceleration, with a significant increase after 2014 (APC + 8.51%). Regionally, the South experienced the steepest post-2013 increase, while the Northeast retained the lowest absolute rates despite a significant rise after 2014. Urban populations showed early improvement through 2014 followed by rising mortality, whereas rural populations experienced a later but steeper rise beginning around 2013, with widening urban–rural disparities over time. Portal hypertension-related mortality has risen significantly since the mid-2010s across all demographic and geographic subgroups, with disproportionate burdens among Hispanic individuals, men, rural populations, and residents of the Southern United States. These findings highlight the urgent need for targeted prevention strategies, equitable access to hepatology care, and aggressive management of metabolic and alcohol-related risk factors to reverse this trajectory.

ABSTRACT MYH11 ‐related hereditary type 2 visceral myopathy is a rare smooth muscle disorder typically presenting in infancy with severe gastrointestinal and genitourinary dysfunction. We describe a 73‐year‐old female with lifelong symptoms of gastrointestinal and urinary dysfunction, including chronic constipation, neurogenic bladder, recurrent urinary tract infections, gastroparesis, and pelvic organ prolapse. A multigenerational family history revealed similar visceral smooth muscle abnormalities among 14 affected individuals over five generations, suggesting autosomal dominant inheritance. Whole‐genome sequencing identified a heterozygous, likely pathogenic variant in MYH11 c.5819del; p.(Pro1940HisfsTer91), consistent with the diagnosis of autosomal dominant type 2 visceral myopathy. This variant causes production of an abnormally elongated myosin‐heavy chain, disrupting muscle contractile function. This individual's survival into her eighth decade reflects long‐term clinical stability, possibly attributable to the variant's milder effect. We describe the clinical course of the disease, along with a comprehensive review of previously described individuals with the same variant. This case broadens the phenotypic spectrum of MYH11 ‐associated visceral myopathy, demonstrating that late‐onset, milder forms can occur and remain compatible with long‐term survival with optimal supportive management. Comprehensive genetic evaluation identifies primary disorders, enabling precise diagnosis, tailored management, and informed genetic counseling for complex phenotypes.