Kevin Brittan

Syndromes characterized by congenital diarrhea, hearing loss, and intrahepatic cholestasis are uncommon and often misdiagnosed as progressive familial intrahepatic cholestasis (PFIC). Recent genetic studies have widened the array of genes linked with cholestatic disorders. Among these, UNC45A has recently been implicated in microvillous inclusion disease (MVID), although only a few cases exist. This case highlights a 20-year-old woman initially diagnosed clinically with PFIC type 1 during childhood. After ileal bypass at age 4 years, she had a resolution of intractable pruritus and cholestasis. Despite remaining symptom-free for over a decade, she returned in adulthood with recurrent cholestatic pruritus. Odevixibat was initiated for presumed PFIC while awaiting additional testing with symptomatic improvement and laboratory normalization. Whole genome sequencing identified novel compound heterozygous mutations in UNC45A and small bowel biopsies confirmed villous atrophy. Odevixibat, currently approved for cholestatic pruritus in PFIC and Alagille syndrome, demonstrates efficacy in managing cholestatic pruritus in MVID.

Idiopathic granulomatous hepatitis is a rare condition characterized by hepatic granulomas with constitutional symptoms such as recurrent fevers, myalgias, and hepatosplenomegaly in the absence of infection or inflammatory disorder. Typical treatment and course of this disease consist of a course of steroids with rapid symptom resolution. However, symptoms may recur when steroids are tapered. In these circumstances, azathioprine, methotrexate, infliximab, and adalimumab have demonstrated good response. In this case, we present a patient who developed antidrug antibodies to infliximab and adalimumab and was the first documented case of this disease to be treated with certolizumab pegol. Our case highlights the novel efficacy of certolizumab pegol for idiopathic granulomatous hepatitis and its role in treating idiopathic granulomatous hepatitis with antidrug antibodies.

Background The Coronavirus disease 2019 (COVID-19) pandemic disrupted patient care and worsened the morbidity and mortality of some chronic diseases. The impact of the COVID-19 pandemic on hospitalizations and outcomes in patients with cirrhosis both before and during different time periods of the pandemic has not been evaluated. Aims Describe characteristics of hospitalized patients with cirrhosis and evaluate inpatient mortality and 30-day readmission before and after the start of the COVID-19 pandemic. Methods Retrospective single-center cohort study of all hospitalized patients with cirrhosis from 2018 to 2022. Time periods within the COVID-19 pandemic were defined using reference data from the World Health Organization and Centers for Disease Control. Adjusted odds ratios from logistic regression were used to assess differences between periods. Results 33,926 unique hospitalizations were identified. Most patients were over age 60 years across all time periods of the pandemic. More Hispanic patients were hospitalized during COVID-19 than before COVID-19. Medicare and Medicaid are utilized less frequently during COVID-19 than before COVID-19. After controlling for age and gender, inpatient mortality was significantly higher during all COVID-19 periods except Omicron compared to before COVID-19. The odds of experiencing a 30-day readmission were 1.2 times higher in the pre-vaccination period compared to the pre-COVID-19 period. Conclusion Inpatient mortality among patients with cirrhosis has increased during the COVID-19 pandemic compared to before COVID-19. Although COVID-19 infection may have had a small direct pathologic effect on the natural history of cirrhotic liver disease, it is more likely that other factors are impacting this population.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal–oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.