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In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Humanos , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Respuesta Virológica SostenidaAsunto(s)
Carcinoma Hepatocelular/cirugía , Procedimientos Quirúrgicos de Citorreducción , Encefalopatía Hepática/cirugía , Hiperamonemia/cirugía , Neoplasias Hepáticas/cirugía , Adulto , Amoníaco/sangre , Carcinoma Hepatocelular/complicaciones , Encefalopatía Hepática/sangre , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , Humanos , Hiperamonemia/sangre , Hiperamonemia/diagnóstico , Hiperamonemia/etiología , Neoplasias Hepáticas/complicaciones , Masculino , Resultado del TratamientoRESUMEN
Purpose of Review: Advancements in our understanding of the hepatitis B viral (HBV) life cycle have paved the way for novel approaches to treat HBV infection. This review summarizes the various strategies being pursued to achieve a functional cure, defined as loss of hepatitis B surface antigen (HBsAg) and absence of viral replication 6 months off-therapy. Recent Findings: Direct acting antiviral, host targeting antiviral, and immunological approaches are in various stages of development as treatment for chronic HBV infection. Summary: Novel treatments are being developed in pursuit of a cure for HBV. Current evidence suggests a single therapeutic agent alone may be insufficient, necessitating the need for combination therapy targeting HBV and the host immune response. Ongoing research focused on identifying the best therapeutic combination holds promise in achieving functional cure for HBV.
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BACKGROUND: Most people with metabolic dysfunction-associated steatotic liver disease (MASLD) lack significant fibrosis and are considered low-risk. Surveillance strategy for low-risk MASLD remains uncertain. AIM: Identify which low-risk subjects can avoid follow-up vibration-controlled transient elastography (VCTE) within 1 year. METHODS: Retrospective analysis of two independent low-risk MASLD cohorts (baseline liver stiffness [LS]â <â 8kPa) with routine 6-12 months follow-up VCTE. The primary outcome was LSâ ≥â 8kPa on follow-up, requiring referral and further work-up according to current guidance. Predictors of the primary outcome on univariate and multivariate logistic regression were incorporated into a decision algorithm, and validated in an independent cohort. RESULTS: Of 206 subjects in the derivation cohort, 96 were low-risk. After a median of 10 months, 24 (25%) low-risk subjects had LSâ ≥â 8kPa. Baseline LS ( P â <â 0.01) and ALT change from baseline ( P â =â 0.02) (multivariate AUROCâ =â 0.84 [0.74-0.94]) predicted the primary outcome, and were incorporated to a two-step decision algorithm. Low-risk subjects with baseline LSâ <â 5.5 kPa can avoid repeating VCTE in a year, while those with LSâ >â 6.8 kPa require one. For intermediate baseline LS (5.5-6.8kPa), repeat VCTE is only indicated when ALT increase > 6 U/L. The algorithm had 92% negative predictive value, 78% specificity, and 78% accuracy in the derivation cohort. In the validation cohort (nâ =â 64), it had 91% NPV, 72% specificity, and 71% accuracy. CONCLUSION: In low-risk MASLD, a simple algorithm combining baseline LS and ALT change can be used to safely avoid a repeat VCTE in a year.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso , Humanos , Estudios Retrospectivos , Hígado Graso/patología , Fibrosis , Valor Predictivo de las Pruebas , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Hígado/patologíaRESUMEN
Purpose of Review: Hepatitis D Virus (HDV), although a small defective virus, poses a substantial public health challenge due to lack of awareness, underrecognized prevalence, and limited treatment options. Universal HDV screening within hepatitis B virus (HBV) cohorts is essential to address this issue. Despite its aggressive nature, effective HDV therapies have remained elusive for over four decades. Recent Findings: Advances in understanding HDV's biology and clinical behavior offer potential therapeutic breakthroughs, fostering optimism. As insights grow, effective and targeted therapies are being developed to improve HDV management. Summary: This review delves into HDV's intricate structure and biology, highlighting formidable hurdles in antiviral development. It emphasizes the importance of widespread screening, exploring noninvasive diagnostics, and examining current and emerging innovative therapeutic strategies. Moreover, the review explores models for monitoring treatment response. In essence, this review simplifies the complexities of effectively combating HDV.
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Porphyria caused by inherited disorders in heme biosynthesis can lead to accumulation of porphyrins in various organs. Liver involvement due to porphyria mostly results in cholestasis leading to liver cirrhosis or hepatocellular carcinoma. Congenital erythropoietic porphyria (CEP), a rare porphyria due to deficiency of uroporphyrinogen III synthase, mostly results in cutaneous manifestations. There are reports of liver involvement including varying degree of fibrosis in patients with CEP. We report a unique case of a patient with CEP who developed porto-sinusoidal vascular disease with complications of portal hypertension that necessitated liver transplantation.
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A granuloma is a discrete collection of activated macrophages and other inflammatory cells. Hepatic granulomas can be a manifestation of localized liver disease or be a part of a systemic process, usually infectious or autoimmune. A liver biopsy is required for the detection and evaluation of granulomatous liver diseases. The prevalence of granulomas on liver biopsy varies from 1% to 15%. They may be an incidental finding in an asymptomatic individual, or they may represent granulomatous hepatitis with potential to progress to liver failure, or in chronic disease, to cirrhosis. This review focuses on pathogenesis, histological features of granulomatous liver diseases, and most common etiologies, knowledge that is essential for timely diagnosis and intervention.
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Hepatopatías , Humanos , Hepatopatías/diagnóstico , Cirrosis Hepática , Granuloma/diagnóstico , BiopsiaRESUMEN
Introduction: Prolidase deficiency is a rare autosomal recessive disorder caused by variants in the PEPD gene. Patients usually have multi-organ involvement and a wide range of clinical features including recurrent skin ulcers, dysmorphic facial features, recurrent infections, intellectual disability, and splenomegaly. Studies have shown that patients with prolidase deficiency may have hepatic manifestations including hepatomegaly and abnormal liver enzymes. However, there is no detailed description of liver disease in this patient population. Case Presentation: Here, we present 3 patients with prolidase deficiency with varying extents of hepatic involvement. Conclusion: Prolidase deficiency patients with liver disease should be followed up long term to understand more about the pathophysiology and the impact of liver disease on long-term outcomes.
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BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.
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Carcinoma Hepatocelular , Procedimiento de Fontan , Cirrosis Hepática , Neoplasias Hepáticas , Humanos , Procedimiento de Fontan/efectos adversos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/etiología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Incidencia , Cuidados PaliativosRESUMEN
BACKGROUND: Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. AIM: We aimed to evaluate disease progression and outcomes in NCPH. METHODS: Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. RESULTS: Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. CONCLUSIONS: Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.
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Progresión de la Enfermedad , Hipertensión Portal , Humanos , Hipertensión Portal/fisiopatología , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Recuento de Plaquetas , Hígado/patología , Hígado/fisiopatología , Anciano , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , BiopsiaRESUMEN
Background: Transient elastography (TE) is an FDA approved, non-invasive tool to estimate liver stiffness measurement (LSM) in patients with non-alcoholic fatty liver disease (NAFLD). Our aim was to analyze if body mass index (BMI) would predict the severity of liver stiffness using TE scores. Methods: We performed a cross-sectional study of patients with NAFLD who presented to the hepatology clinic between January 2019 through January 2021. Fibrosis severity was divided into the following categories: F0 to F1 (2-7 kPa), F2 (>7 to 10 kPa), F3 (>10 to 14 kPa) and F4 (>14 kPa). We used ordered logistic regression models to determine the odds ratio (OR) and 95% confidence interval (CI) of having a higher LSM severity compared to lower associated with BMI. Models were adjusted for patient demographics and comorbidities. Results: Among 284 patients, 56.7% were females, and the median (interquartile range, IQR) age was 62 [51-68] years and BMI 31.9 (28.1, 36.2) kg/m2; 47% of patients were in the F0 to F1 stage, 24% F2, 16% F3, and 13% F4. The correlation between BMI and TE score was 0.31 (P<0.001). With 1 kg/m2 increase in BMI there was 1.10 times higher odds of having a higher LSM severity (adjusted OR, 1.10; 95% CI: 1.05-1.14). Compared to patients with BMI <25 kg/m2, the adjusted OR (95% CI) of having a higher fibrosis stage was 1.82 (0.61-5.44), 5.93 (2.05-17.13), and 8.56 (2.51-29.17) for patients with BMI of 25 to <30, 30 to <40, and ≥40 respectively. Conclusions: BMI correlates with the severity of LSM using TE scores in NAFLD patients even after adjusting for potential confounding variables. This suggests TE as an appreciable study for liver stiffness even in obese individuals.
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A 58-year-old female patient presented with altered mental status, diarrhea, and fever. She was hospitalized for acute kidney injury [AKI] and a patchy right lower lobe infiltrates on chest X-ray. Subsequent testing revealed rhabdomyolysis and a positive urinary Legionella antigen test. Creatinine kinase [CK] level peaked at 512,820 U/L and was managed with aggressive intravenous hydration and appropriate antibiotic treatment. With clinical signs of resolution of pneumonia, the CK level declined rapidly, however renal function returned to baseline only after 2 months requiring hemodialysis in the meantime. The patient was also on tofacitinib which can rarely contribute to rhabdomyolysis. Legionella infection can cause severe rhabdomyolysis and AKI. Timely diagnosis of Legionella-associated rhabdomyolysis, and prompt treatment with aggressive IV hydration and appropriate antibiotics is required to prevent morbidity and mortality.
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A 33-year-old previously healthy man from Mexico who presented with massive hemoptysis, fevers, chills and found to have cavitary lesions in the right upper lobe of lung was highly suspicious for tuberculosis. The patient was treated with vancomycin, ceftriaxone, azithromycin and placed on isolation for suspected tuberculosis. Sputum AFB stains were negative and blood cultures grew Group A Streptococcus [GAS]. Antibiotics were narrowed down to ampicillin-sulbactam and the patient was discharged with significant clinical improvement. Strep A pyogenes is a rare cause of cavitary hemorrhagic pneumonia but is associated with high mortality. Clinical suspicion and early diagnosis are crucial in saving the patient.
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A 59-year-old Baltimore native female, with a history of asthma and no history of travel outside of the USA, presented with productive cough and shortness of breath. Computed tomography scan showed left upper lobe consolidation of the lung with multiple tiny cavitations. She was empirically treated without improvement. Later, strongyloides were found in the sputum gram stain and she was treated with ivermectin. Pulmonary strongyloidiasis has been mainly described in patients who are immunosuppressed and have a history of travel to endemic areas, both of which were absent in our patient. Our case underlines the importance of considering strongyloides necrotizing pneumonia as a differential diagnosis of community-acquired pneumonia even in immunocompetent patients in the USA, especially if not responding to empiric treatment.
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Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, rapidly progressive, primary intestinal T-cell lymphoma. It is most commonly seen in the Asian and Hispanic populations and is usually not related to celiac disease, unlike type I enteropathy associated T-cell lymphoma. The most common site of occurrence is the small intestine. Patients usually present during the advanced stage of disease with clinical features of intestinal perforation or obstruction. The late clinical presentation and lack of targeted therapy are factors contributing to its poor prognosis. Here, we are presenting the case of a patient who initially came to the hospital for a urinary tract infection. As his abdominal CT scan showed abdominal wall thickening, he underwent further workup which revealed the diagnosis of MEITL.