Absence Of Cirrhosis Research Articles

Viral hepatitis in persons living with HIV in the post-COVID era.

Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.

ThP5.8 - Familial hepatocellular carcinoma: a model for studying preventive and therapeutic measures

Abstract Aims Limited attention has been given to the role of primary genetic factors in hepatocellular carcinoma (HCC) especially as familial clusters of HCC are mostly described in areas of endemic hepatitis B virus (HBV) infection. The aim of the study was to review the literature on familial hepatocellular carcinoma (FHCC) and give evidence to suggest that FHCC may be a good model for studying preventive and therapeutic measures for HCC Methods Electronic searches of the Medline (PubMed) data base were performed to identify original published case studies on familial HCC. Results 16 case studies on FHCC were reported between 1965-2016. Even in the presence of HBV infection, FHCC seemed statistically unlikely to occur by chance. Genetic contributions may explain healthy and unhealthy HBsAg carriers, the male sex being predominantly affected, and HBV being directly oncogenic and causing HCC in the absence of cirrhosis in the younger patients. The highest risk of HCC occurs when a hereditary component is acting in concert with environmental factors such as HBV infection through epigenomic alterations. A family history of HCC increases the risk of FHCC independently of hepatitis due to a multifactorial inheritance including DICER 1 germline mutation and altered liver zonation. Epigenetic studies on monozygotic twins with HCC will identify the susceptible loci which can be used therapeuticallym. FHCC is a prognostic factor for improved survival in early resectable tumours with no/minimal cirrhosis. Conclusions HCC lacks a strong hereditary component but HCC-prone families of the familial type may provide a powerful model for studying preventive and therapeutic measures.

Metabolomic profiles differentiate between porto-sinusoidal vascular disorder, cirrhosis, and health

Background & AimsPorto-sinusoidal vascular disorder (PSVD) is a rare and diagnostically challenging vascular liver disease. This study aimed to identify distinct metabolomic signatures in patients with PSVD, cirrhosis, and healthy volunteers (HV) to facilitate non-invasive diagnosis and elucidate perturbed metabolic pathways. MethodsSerum samples from 20 HV and patients with histologically confirmed PSVD or cirrhosis were analyzed. Metabolites were measured using liquid chromatography-mass spectrometry (LC-MS). Differential abundance was evaluated with Limma’s moderated t-statistics. Artificial neural network (ANN) and support vector machine (SVM) models were developed to classify PSVD against cirrhosis or HV metabolomic profiles. An independent cohort was used for validation. ResultsA total of 283 metabolites were included for downstream analysis. Clustering effectively separated PSVD metabolomes from HV, although a subset of PSVD patients (n=5, 25%) overlapped with cirrhosis. Differential testing revealed significant PSVD-linked metabolic perturbations, including taurocholic and adipic acids, distinguishing PSVD from both HV and cirrhosis. Alterations in pyrimidine, glycine, serine, and threonine pathways were exclusively associated with PSVD. Machine learning models utilizing selected metabolic signatures reliably differentiated PSVD from HV or cirrhosis using only 4 to 6 metabolites. Validation in an independent cohort demonstrated the high discriminative ability of taurocholic acid (AUROC 0.899) for PSVD vs HV and the taurocholic acid/aspartic acid ratio (AUROC 0.720) for PSVD vs cirrhosis. ConclusionsHigh-throughput metabolomics enabled the identification of distinct metabolic profiles for differentiating PSVD, cirrhosis, and healthy individuals. Unique alterations in the glycine, serine, and threonine pathways suggest their potential involvement in PSVD pathogenesis. Impact And ImplicationsPorto-sinusoidal vascular disorder (PSVD) is a vascular liver disease that can lead to pre-sinusoidal portal hypertension in the absence of cirrhosis, with poorly understood pathophysiology and no established treatment. Our study demonstrates that analyzing the serum metabolome could reveal distinct metabolic signatures in PSVD patients, including alterations in the pyrimidine, glycine, serine and threonine pathways and potentially shedding light on the disease's underlying pathways. These findings hold potential for earlier and non-invasive diagnosis of PSVD, potentially reducing reliance on invasive procedures like liver biopsy and guiding diagnostic pathways.

MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis

Background and AimsDespite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic liver remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods354 patients with MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018, were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results35% of HCC cases occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Non-cirrhotic patients were older, had a greater tumor burden, but also better liver function than cirrhotic patients. Non-cirrhotic patients showed better overall survival than those with cirrhosis (p=0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Non-cirrhotic patients underwent surgery more frequently than cirrhotic patients did (41% versus 11%, p<0.001), even in cases where the largest tumors were ≥5 cm (42% versus 14%, p=0.002) or there were four or more lesions (19% versus 2%, p=0.024). Among the cirrhotic and non-cirrhotic patients who underwent surgery, survival was not significantly different. The cirrhosis / no cirrhosis ratio remained stable over the study period. ConclusionsIn MASLD-related HCC, non-cirrhotic patients account for 35% of cases and have poor prognostic factors (higher age and larger tumors) but also better liver function, resulting in more aggressive management of advanced tumors and better survival compared to cirrhotic patients. Impact and implicationsThe incidence of hepatocellular carcinoma related to MASLD is projected to increase by 47% to 130% by year 2030 with one third occurring in non cirrhotic livers, making them inaccessible to screening with tumors more advanced at diagnosis. Our study shows that survival in MASLD patients with hepatocellular carcinoma relies on age, tumor burden and underlying liver function and the preserved liver function of these non-cirrhotic patients allows them to be managed surgically. A better understanding of the pathophysiological processes driving HCC occurrence in non-cirrhotic MASLD patients to screen and early management of these patients.

Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19

The underlying mechanisms and clinical impact of portal microthrombosis in severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesised that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19. Ninety-three patients who died from COVID-19 were analysed for portal microvascular damage (histology), IPVD (histology and chest-computed tomography, CT), and hypoxemia (arterial blood gas). Seventeen patients who died from COVID-19-unrelated pneumonia served as controls. Vascular lesions and microthrombi were phenotyped for endothelial (vWF) and pericyte (αSMA/PDGFR-β) markers, tissue factor (TF), viral spike protein and nucleoprotein (SP, NP), fibrinogen, and platelets (CD41a). Viral particles in vascular cells were assessed by transmission electron microscopy. Cultured pericytes were infected with SARS-CoV-2 to measure TF expression and tubulisation of human pulmonary microvascular endothelial cells was assessed upon vWF treatment. IPVD was present in 16/66 patients with COVID-19, with available liver and lung histology, and was associated with younger age (62 vs. 78 years-old), longer illness (25 vs. 14 days), worsening hypoxemia (PaO2/FiO2 from 209 to 89), and an increased requirement for ventilatory support (63% vs. 22%) compared to COVID-19/Non-IPVD. IPVD, absent in controls, was confirmed by chest CT. COVID-19/IPVD liver histology showed portal microthrombosis in >82.5% of portal areas, with a thicker wall of αSMA/PDGFR-β+/SP+/NP+ pericytes compared with COVID-19/Non-IPVD. Thrombosed portal venules correlated with αSMA+ area, whereas infected SP+/NP+ pericytes expressed TF. SARS-CoV-2 viral particles were observed in portal pericytes. Invitro SARS-CoV-2 infection of pericytes upregulated TF and induced endothelial cells to overexpress vWF, which expanded human pulmonary microvascular endothelial cell tubules. SARS-CoV-2 infection of liver pericytes elicits a local procoagulant response associated with extensive portal microthrombosis, IPVD and worsening respiratory failure in fatal COVID-19. Vascular involvement of the liver represents a serious complication of COVID-19 infection that must be considered in the work-up of patients with long-lasting and progressively worsening respiratory failure, as it may associate with the development of intrapulmonary vascular dilations. This clinical picture is associated with a procoagulant phenotype of portal venule pericytes, which is induced by SARS-CoV-2 infection of pericytes. Both observations provide a model that may apply, at least in part, to other vascular disorders of the liver, featuring obliterative portal venopathy, similarly characterised at the clinical level by development of hypoxemia and at the histological level by phlebosclerosis and reduced calibre of the portal vein branches in the absence of cirrhosis. Moreover, our findings shed light on an overlooked player in the pathophysiology of thrombosis, i.e. pericytes, which may present a novel therapeutic target.

Prognostic factors in patients with hepatocellular cancer with progression after liver transplantation

Introduction. Hepatocellular cancer is the most frequent primary malignant neoplasm of the liver, developing against the background of viral hepatitis, alcohol abuse, metabolic disorders, cirrhosis. Most often hepatocellular cancer is diagnosed at late stages of the disease, when patients are no longer subject to specific treatment. The priority method of treatment of early stages remains surgical. In the absence of cirrhosis or with compensated cirrhosis the best option is liver resection, in other cases orthotopic liver transplantation is performed. However, when hepatocellular cancer is diagnosed, most patients fall outside the Milan criteria, and the bridge to orthotopic liver transplantation is down-stage therapy. Bridge therapy is used to treat hepatocellular cancer while awaiting liver transplantation and aims to prevent stage progression. The probability of progression of hepatocellular cancer after orthotopic liver transplantation within the first two years is about 75% and about 10% is detected after the fourth year. Progression of hepatocellular cancer remains the main factor limiting the life expectancy of patients after orthotopic liver transplantation.The aim of the study: to evaluate the results of antitumor treatment of patients with hepatocellular cancer progression after liver transplantation.Materials and methods. We evaluated the results of treatment of 50 patients with hepatocellular cancer progression after orthotopic liver transplantation, who were treated on the basis of FGBU NMI Center of Oncology named after N.N. Blokhin. N.N. Blokhin Oncology Center in the period from 2009 to 2020. We analyzed and evaluated overall and recurrence-free survival depending on the bridge therapy, type of treatment, presence of vascular invasion and portal vein thrombosis.Results. According to the results of bridge therapy, hepatocellular cancer stage progression was observed in 9 patients, stabilization - in 17 patients, partial/complete response – in 9 patients. The median recurrence-free survival of patients who received bridge therapy and down-stage therapy was 23.6 months; among patients who did not, it was 35.6 months. The median overall survival with surgical treatment was 79.8 months, whereas with radiation therapy it was 17.2 months. Conclusions. In the studied group of patients the treatment was tolerated satisfactorily. Optimization of immunosuppression protocol and modification of dose regimens of systemic therapy is considered as a condition for treatment, which leads to improvement of long-term treatment results (overall and relapse-free survival).

PNPLA3 risk allele is associated with risk of hepatocellular carcinoma but not decompensation in compensated cirrhosis.

The PNPLA3-rs738409-G, TM6SF2-rs58542926-T, and HSD17B13-rs6834314-A polymorphisms have been associated with cirrhosis, hepatic decompensation, and HCC. However, whether they remain associated with HCC and decompensation in people who already have cirrhosis remains unclear, which limits the clinical utility of genetics in risk stratification as HCC is uncommon in the absence of cirrhosis. We aimed to characterize the effects of PNPLA3, TM6SF2, and HSD17B13 genotype on hepatic decompensation, HCC, and liver-related mortality or liver transplant in patients with baseline compensated cirrhosis. We conducted a single-center retrospective study of patients in the Michigan Genomics Initiative who underwent genotyping. The primary predictors were PNPLA3, TM6SF2, and HSD17B13 genotypes. Primary outcomes were either hepatic decompensation, HCC, or liver-related mortality/transplant. We conducted competing risk Fine-Gray analyses on our cohort. We identified 732 patients with baseline compensated cirrhosis. During follow-up, 50% of patients developed decompensation, 13% developed HCC, 24% underwent liver transplant, and 27% died. PNPLA3-rs738409-G genotype was associated with risk of incident HCC: adjusted subhazard hazard ratio 2.42 (1.40-4.17), p=0.0015 for PNPLA3-rs738409-GG vs. PNPLA3-rs738409-CC genotype. The 5-year cumulative incidence of HCC was higher in PNPLA3-rs738409-GG carriers than PNPLA3-rs738409-CC/-CG carriers: 15.6% (9.0%-24.0%) vs. 7.4% (5.2%-10.0%), p<0.001. PNPLA3 genotype was not associated with decompensation or the combined outcome of liver-related mortality or liver transplant. TM6SF2 and HSD17B13 genotypes were not associated with decompensation or HCC. The PNPLA3-rs738409-G allele is associated with an increased risk of HCC among patients with baseline compensated cirrhosis. People with cirrhosis and PNPLA3-rs738409-GG genotype may warrant more intensive HCC surveillance.

Current concepts in the management of non-cirrhotic non-malignant portal vein thrombosis.

Non-cirrhotic non-malignant portal vein thrombosis (NCPVT) is an uncommon condition characterised by thrombosis of the portal vein, with or without extension into other mesenteric veins, in the absence of cirrhosis or intra-abdominal malignancy. Complications can include intestinal infarction, variceal bleeding and portal biliopathy. In this article, we address current concepts in the management of NCPVT including identification of risk factors, classification and treatment, and review the latest evidence on medical and interventional management options.

Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

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. We aimed to evaluate disease progression and outcomes in NCPH. 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. 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. 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.

Factors Positively Correlated with Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B.

Chronic hepatitis B virus (HBV) infection is a global public health challenge since more than 250 million individuals are affected worldwide. Since different treatment modalities are available and not all patients are candidates for antiviral treatment, biomarkers that potentially predict the possibility of HBsAg clearance and seroconversion may be useful in clinical practice. In this retrospective study, we aimed to identify factors positively correlated with HBsAg seroconversion in a large cohort of 371 chronic hepatitis B patients treated at a German tertial center between 2005 and 2020. Seroconversion occurred in 25/371 (6.7%) and HBsAg loss in 29/371 patients (7.8%) with chronic HBV infection. Antiviral therapy was associated with a lower chance of seroconversion (seroconversion antiviral therapy 14/260 (5.4%) vs. therapy-naïve patients 11/111 (9.9%), p = 0.027). Seroconversion rates were higher in patients with (very) low titers of HBV DNA (best cut-off value 357 IU/mL) and quantitative HBsAg. The best cut-off value with regard to seroconversion was 357 IU/mL for HBV DNA (AUC 0.693 (95%-CI 0.063-0.422), sensitivity 0.714, specificity 0.729; p < 0.0005) and 33,55 IU/mL for HBsAg (AUC 0.794 (95%-CI 0.651-0.937), sensitivity 0.714, specificity 0.949; p < 0.0005). However, male gender was positively associated with seroconversion (seroconversion: males 7.6% vs. females 2.7%, p = 0.036). Treatment-naïve male chronic HBV patients with low viral load and inflammatory activity have the best chance to achieve seroconversion. In the absence of cirrhosis, antiviral therapy should therefore not be performed in this patient collective.

MASLD-Related HCC-Update on Pathogenesis and Current Treatment Options.

Hepatocellular carcinoma (HCC) is a common complication of chronic liver diseases and remains a relevant cause of cancer-related mortality worldwide. The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) as a risk factor for hepatocarcinogenesis is on the rise. Early detection of HCC has been crucial in improving the survival outcomes of patients with metabolic dysfunction-associated steatohepatitis (MASH), even in the absence of cirrhosis. Understanding how hepatocarcinogenesis develops in MASH is increasingly becoming a current research focus. Additive risk factors such as type 2 diabetes mellitus (T2DM), genetic polymorphisms, and intestinal microbiota may have specific impacts. Pathophysiological and epidemiological associations between MASH and HCC will be discussed in this review. We will additionally review the available tumor therapies concerning their efficacy in MASH-associated HCC treatment.

Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide.

Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019. In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. NASH-related HCC has characteristics that differ from those of virus-associated HCC. Compared with other etiologies, patients with NASHassociated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.

A Prospective Analysis of the Effects of a Powder-Type Hemostatic Agent on the Short-Term Outcomes after Liver Resection.

Background and Objectives: Postoperative bleeding is a significant cause of morbidity and mortality following liver resection. Therefore, it is crucial to minimize bleeding during liver resection and effectively manage it when it occurs. Arista® AH (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) is a microporous polysaccharide hemosphere (MPH), a new plant-derived polysaccharide powder hemostat that can be applied to the entire surgical field. This study prospectively assessed the effectiveness of Arista for bleeding control when applied intraoperatively to the liver resection surface. Materials and Methods: Data were collected at Seoul National University Bundang Hospital for patients who underwent liver resection owing to malignant hepatocellular carcinoma or benign liver diseases. We compared the outcomes between 45 patients managed with Arista® AH (data were prospectively collected between September 2022 and May 2023) and 156 patients managed without the use of Arista® AH (data were retrospectively collected between January 2021 and December 2021). Results: There were no significant differences in patient characteristics between the two groups. The estimated blood loss (EBL) was significantly lower in the Arista® AH group compared with the control group (495.56 ± 672.7 mL vs. 691.9 ± 777.5 mL, p = 0.049). The mean postoperative hospital stay was significantly shorter in the Arista® AH group (5.93 ± 1.88 days vs. 6.94 ± 4.17 days, p = 0.024). The time to Jackson-Pratt drain removal was also significantly shorter in the Arista® AH group (4.64 ± 1.31 days vs. 5.30 ± 2.87 days, p = 0.030). The patient subgroup was divided into four categories based on the type of resection and the presence or absence of cirrhosis. Within the subgroup of major resections in non-cirrhotic patients, the Arista® AH group demonstrated significantly better outcomes compared to the control group, showed lower EBL, reduced need for blood transfusions, decreased volume of drain fluid collected within 48 h, earlier removal of drains, and shorter hospital stays. In contrast, for the other subgroups such as minor resection (both non-cirrhotic and cirrhotic) and major resection with cirrhosis, the differences between the Arista® AH and control groups in various parameters like EBL, blood transfusion rates, drain fluid volume, time to drain removal, and duration of hospital stay were not statistically significant. Conclusions: Arista® AH significantly improved intraoperative blood management and postoperative recovery in patients undergoing liver resection, particularly in non-cirrhotic patients who underwent major resection.

Efficacy and safety of DAA in children and adolescents with chronic HCV infection: A systematic review and meta-analysis.

We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines. We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach. A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes. CRD42020146752.

The adverse characteristics of hepatocellular carcinoma in the non-cirrhotic liver disproportionately disadvantage Black patients.

Black patients have higher hepatocellular carcinoma (HCC)-related mortality than White patients and more often develop HCC in non-cirrhotic liver. HCC surveillance is primarily directed toward cirrhotic patients. We aimed to characterize HCC in non-cirrhotic patients and to identify factors associated with HCC beyond Milan criteria. Demographic, imaging, laboratory, and pathology data of HCC patients at our institution, 2003-2018, were reviewed, retrospectively. Race/ethnicity were self-reported. Cirrhosis was defined as a Fibrosis-4 score ≥3.25. Compared to 1146 cirrhotic patients, 411 non-cirrhotic patients had larger tumors (median 4.7 cm vs. 3.1 cm, p < 0.01) and were less likely to be within Milan criteria (42.6% vs. 57.7%, p < 0.01). Among non-cirrhotic patients, Black patients had larger tumors (4.9 cm vs. 4.3 cm, p < 0.01) and a higher percentage of poorly differentiated tumors (39.4% vs. 23.1%, p = 0.02). Among cirrhotic patients, Black patients had larger tumors (3.3 cm vs. 3.0 cm, p = 0.03) and were less likely to be within Milan criteria (52.3% vs. 83.2%, p < 0.01). In multivariable analysis, lack of commercial insurance (OR 1.45 [CI 95% 1.19-1.83], p < 0.01), male sex (OR 1.34 [CI 95% 1.05-1.70], p < 0.01), absence of cirrhosis (OR 1.58 [CI 95% 1.27-1.98], p < 0.01) and Black race/ethnicity (OR 1.34 [CI 95% 1.09-1.66], p = 0.01) were associated with HCC beyond Milan criteria. Black patients had lower survival rates than other patients (p < 0.01). Non-cirrhotic patients had more advanced HCC than cirrhotic patients. Black patients (with or without cirrhosis) had more advanced HCC than comparable non-Black patients and higher mortality rates. Improved access to healthcare (commercial insurance) may increase early diagnosis (within Milan criteria) and reduce disparities.

Porto-sinusoidal vascular disorder in chronic HBV: A significant coexistence not to be overlooked

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of liver diseases with vascular abnormalities that can cause portal hypertension in the absence of cirrhosis. The new diagnostic criteria allow for coexistence with other liver diseases, however its relationship with chronic hepatitis B (CHB) remains unclear. This study aimed to assess HBV prevalence in a PSVD cohort and evaluate its clinical impact. This retrospective study was conducted on patients with PSVD at Hospital Clínic Barcelona. HBV serology was evaluated, and patients were categorized into HBV chronic infection, past infection, or no HBV exposure. Clinical characteristics and outcomes were compared. We included 155 patients with PSVD. Prevalence of CHB and past HBV infection in patients with PSVD was higher than in the general population (5.8% vs. 0.5%, p <0.0001 and 20% vs. 9.1%, p <0.0001, respectively). Patients with CHB had a significant delay in PSVD diagnosis compared to those without CHB (11 [5-25] vs. 1 [0-3] years, p= 0.002) and had a more advanced disease (MELD score 12 [9-17] vs. 9 [7-11], p= 0.012) at the time of PSVD diagnosis. The clinical evolution of PSVD in patients with CHB was marked by a significantly higher transplantation rate at the last follow-up (33% vs. 4.1%, p= 0.001). Recognizing the coexistence of PSVD and CHB is important for timely diagnosis and optimal management, highlighting the potential benefits of specialized care for potentially improved outcomes. The new diagnostic criteria for porto-sinusoidal vascular disorder (PSVD) allow for coexistence with other liver diseases. The results of the present study highlight, for the first time, a non-negligible prevalence of chronic hepatitis B in the PSVD population that was previously unknown. Coexistence may challenge and delay the PSVD diagnosis and is associated with a more unfavorable clinical course. Our findings will increase awareness of this coexistence and improve PSVD diagnosis and management. Furthermore, the data will encourage new studies to determine the prevalence and clinical behavior of other chronic liver diseases that coexist with PSVD.

A nomogram based on psoas muscle index predicting long-term cirrhosis incidence in non-cirrhotic patients with HBV-related acute‑on‑chronic liver failure

There is a lack of scoring system to predict the occurrence of cirrhosis in individuals with acute-on-chronic liver failure (ACLF) in the absence of cirrhosis. The goal of this study was to develop a psoas muscle index (PMI)-based nomogram for cirrhosis risk in non-cirrhotic patients with HBV-related ACLF. We included 274 non-cirrhotic HBV-ACLF patients who were randomly assigned to training and validation groups. Logistic analyses were performed to identify risk factors for cirrhosis. A nomogram was then constructed. The predictive performance of the nomogram was assessed using the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA). During the 360-day follow-up, 44.5% (122/274) of non-cirrhotic HBV-ACLF patients developed cirrhosis. A higher PMI at the L3 level was correlated with a decreased risk of long-term cirrhosis occurrence (OR 0.677, 95% CI 0.518–0.885, P = 0.004). The nomogram incorporating PMI, age, neutrophil-to-lymphocyte ratio (NLR), and international normalized ratio (INR), indicated satisfactory predictive performance for cirrhosis risk stratification in ACLF population. The nomograms had an AUROC of 0.812 (95% CI 0.747–0.866) and 0.824 (95% CI 0.730–0.896) in the training and validation cohorts, respectively. The calibration curves displayed excellent predictive accuracy of the nomogram in both sets. In both cohorts, the DCA verified the nomogram's clinical efficacy. In non-cirrhotic HBV-ACLF patients, a greater PMI appears to protect against long-term cirrhosis occurrence. Strong predictive performance has been demonstrated by PMI-based nomograms in assessing the likelihood of 1-year cirrhosis in those with HBV-ACLF.

Non-Cirrhotic Portal Hypertension: An Update of Diagnosis and Management

Portal hypertension is not the only caused by liver cirrhosis. Non-cirrhotic portal hypertension (NCPH) is characterized by elevated portal pressure in the absence of cirrhosis and is often underdiagnosed in daily clinical practice. The clinical manifestations of NCPH are similar to liver cirrhosis. The diagnosis of NCPH is still challenging due to the various underlying etiologies and often require either non-invasive or invasive examination. Laboratory examination, abdominal ultrasound, endoscopic procedure, hepatic venous gradient measurement, and liver biopsy have role in diagnosis of NCPH. The principle management of NCPH is to treat portal hypertension and its complications, such as prophylaxis and acute management of variceal bleeding, anticoagulants, surgery, splenectomy, and liver transplantation.

Liver Transplantation in a Woman with Mahvash Disease

SummaryMahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.

A Unique Presentation of Familial Idiopathic Colonic Varices

ABSTRACT Colonic varices typically occur in the setting of portal hypertension, and patients may present with rectal bleeding or occult anemia. Idiopathic colonic varices occur infrequently in the absence of cirrhosis and can involve the entire colon. We present a case of a 54-year-old Eastern European woman who had undergone diagnostic colonoscopy for newly diagnosed sigmoid adenocarcinoma and was incidentally found to have colonic varices with normal portal pressure gradients. Her 38-year-old daughter was found to have similar varices, raising concerns for hereditary etiology.