Navigating Complex Challenges: Preoperative Assessment and Surgical Strategies for Liver Resection in Patients with Fibrosis or Cirrhosis.

This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes.

Splenomegaly is a marker of advanced chronic liver disease and portal hypertension in HIV infection.

OBJECTIVES: To evaluate the clinical significance of splenomegaly as a marker of underlying liver disease in people with HIV (PWH). METHODS: We included consecutive PWH from a prospective cohort from 2010 to 2020 with available liver stiffness measurement (LSM) and liver imaging to define splenomegaly (> 13 cm) within 1 year. Cut-offs of LSM > 10 kPa and > 21 kPa were used to identify advanced chronic liver disease (ACLD) and portal hypertension, respectively. Logistic regression multivariable analysis was employed to identify independent predictors of ACLD. RESULTS: In all, 331 PWH were included, 76% of them men, with a median (interquartile range) age of 51.3 (45-58) years, all receiving antiretroviral treatment, and 53% were HIV monoinfected. The PWH with splenomegaly exhibited a higher prevalence of ACLD compared with those with normal spleen size, as per LSM (26% vs. 9%; p = 0.009). Portal hypertension diagnosed by LSM was also more prevalent in PWH with splenomegaly than in those without (15% vs. 2%; p < 0.001). Independent predictors of ACLD were viral hepatitis coinfection [adjusted odds ratio (aOR) = 3.15, 95% confidence interval (CI): 1.65-6.0], lower platelets (aOR = 0.99, 95% CI: 0.99-0.99) and splenomegaly (aOR = 2.41, 95% CI: 1.17-4.99). In patients with available oesophagogastroduodenoscopy, splenomegaly was also associated with higher prevalence of oesophageal varices and other endoscopic findings of portal hypertension (38% vs. 17%; p = 0.027). CONCLUSIONS: Splenomegaly identified on routine imaging may have utility as a marker of ACLD and portal hypertension, prompting further investigations.

Diagnosis of liver fibrosis in ageing patients with HIV at risk for non-alcoholic fatty liver disease in Italy and Canada: assessment of a two-tier pathway.

BACKGROUND: Since the introduction of effective antiretroviral therapy, liver-related mortality has increased ten-fold in ageing people with HIV. This trend is driven by ageing-related metabolic conditions that cause non-alcoholic fatty liver disease (NAFLD), which affects 35-65% of people with HIV. Clinically significant (stage 2-4) liver fibrosis develops in over 15% of people with HIV who have NAFLD. Strategies are needed to identify people with HIV at risk for significant liver fibrosis and reduce cirrhosis-related complications. Non-invasive tests to diagnose liver fibrosis include ultrasound-based transient elastography and serum biomarkers. Transient elastography is a feasible tool to assess liver fibrosis, but it is not largely accessible in HIV clinics. We aimed to determine whether a two-tier care pathway with assessment of simple serum biomarkers for fibrosis as first tier could reduce the need for the specialist transient elastography test (second tier). METHODS: Patients were consecutively identified through a clinical programme for liver disease in people with HIV in Canada and Italy. We applied a two-tier care pathway to three prospective cohorts of people with HIV at risk for NAFLD, defined as those with elevated liver transaminases, body mass index (BMI) of 25 or greater, or diabetes. Patients with alcohol abuse or coinfection with hepatitis B or C viruses were excluded. Five simple serum biomarkers of fibrosis, based on liver transaminases, platelets, and BMI (fibrosis-4 index [FIB-4], BARD [BMI, AST to ALT ratio, diabetes] score, NAFLD fibrosis score, AST to ALT ratio, and AST-to-platelet ratio index [APRI]) were applied as a first-tier assessment to exclude significant liver fibrosis. All patients then received transient elastography. We assessed the decrease in referral for transient elastography that would have occurred based on biomarker assessment and discordance between high transient elastography (≥7·1 kPa), indicating significant liver fibrosis, and low serum fibrosis biomarkers (FIB-4 <1·3, BARD score 0-1, NAFLD fibrosis score less than -1·455, AST to ALT ratio <0·8, and APRI <0·5). We also assessed independent factors associated with that discordance by multivariable logistic regression analysis. FINDINGS: We included 1202 people with HIV at risk for NAFLD (mean age 51·2 years [SD 10·1], 914 [76%] male and 288 [24%] female, mean HIV duration 16·3 years [SE 9·7], mean BMI 26·5 Kg/m2 [SD 4·5]; prevalence of diabetes 49·5%). 222 (18·5%) of these participants had significant liver fibrosis according to transient elastography. Assessment of simple fibrosis biomarkers would have decreased transient elastography referrals between 22·5% (BARD score) and 82·4% (APRI). Discordance rate ranged from 3·9% (NAFLD fibrosis score) to 11·1% (APRI). After adjustment for age, sex, presence of diabetes, level of HDL cholesterol, and CD4 cell count, BMI (odds ratio 1·12, 95% CI 1·07-1·17) and triglyceride level (1·25, 1·08-1·46) were independent predictors of discordance for low APRI and high transient elastography. INTERPRETATION: Use of a two-tier pathway to identify liver fibrosis in ageing people with HIV at risk for NAFLD could reduce transient elastography examinations by a substantial proportion, reducing costs and helping to optimise use of resources in HIV care. FUNDING: GS is supported by a Senior Salary Award from Fonds de recherche du Québec-Santé (number 296306).

Two-Tier Care Pathways for Liver Fibrosis Associated to Non-Alcoholic Fatty Liver Disease in HIV Mono-Infected Patients.

(1) Background: Developing strategies to identify significant liver fibrosis in people with HIV (PWH) is crucial to prevent complications of non-alcoholic fatty liver disease (NAFLD). We aim to investigate if five simple serum biomarkers applied to PWH can optimize a care pathway to identify significant liver fibrosis defined by transient elastography (TE). (2) Methods: A two-tier fibrosis pathway was applied to three prospective cohorts of PWH undergoing TE with CAP. NAFLD was diagnosed as a controlled attenuation parameter ≥ 248 dB/m. Five simple fibrosis biomarkers (FIB-4 < 1.3, BARD score 0-1, NAFLD fibrosis score < -1.455, AST:ALT ratio < 0.8 and APRI < 0.5) were applied as first-tiers to exclude significant liver fibrosis. We determined the decrease in referral for TE that would have occurred based on biomarker assessment and the discordance between low simple fibrosis biomarkers and high TE (≥7.1 kPa), indicating significant liver fibrosis. (3) Results: Of the 1749 consecutive PWH, 15.1% had significant liver fibrosis by TE and 39.1% had NAFLD. The application of the fibrosis biomarkers as first tiers would have resulted in a decrease in TE referrals between 24.9% (BARD score) and 86.3% (APRI). The lowest discordance rate was with NAFLD fibrosis score (8.5%). After adjustments, BMI (odds ratio (OR) 1.12, 95% CI: 1.08-1.17) and triglycerides (OR 1.26, 95% CI: 1.11-1.44) were independent predictors of discordance for APRI < 0.5 and TE ≥ 7.1. The performance of the two-tier pathways was similar in PWH with and without NAFLD. (4) Conclusions: Implementing a two-tier pathway could save a substantial proportion up of TE examinations, reducing costs and helping resource optimization in HIV care. Patients with metabolic risk factors for NAFLD and low fibrosis biomarker may still be considered for TE referral.

Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta-analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. METHODS: Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random-effect model, and heterogeneity was addressed through I 2. Subgroup analyses and meta-regression for various covariates were performed. RESULTS: Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5-fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20-2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27-5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85-2.67) and Asia (OR 2.63, 95% CI 2.20-3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44-2.71 and OR 3.39, 95% CI 2.42-4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta-regression, with a regression coefficient of -2.219 (95% CI -3.927 to -0.511) and -1.929 (95% CI -3.776 to -0.0826), respectively. CONCLUSIONS: This meta-analysis indicates that premenopausal PCOS patients are associated with 2.5-fold increase in the risk of NAFLD, and BMI seems to be the main cofactor.

Acute liver failure in ruptured sinus of Valsalva aneurysm.

A sinus of Valsalva aneurysm (SOVA) is a rare cardiac defect in which the aortic root area between the aortic annulus and the sinotubular junction is dilated. We present a case of acute liver failure (ALF) in a 21-year-old man secondary to ruptured SOVA inducing severe ischemic hepatitis. The patient presented clinically with classical ALF. The liver ultrasound reported hepatomegaly with pulsatile portal flow and dilated hepatic veins. A transthoracic echocardiogram revealed focal aneurysmal dilatation of the aortic root with flow across the aneurysm toward the right atrium and elevated right chambers pressures. The surgical repair of the non-coronary SOVA was successful, and post-operatively, liver transaminases improved, and ALF resolved. Given that ruptured SOVA can be surgically repaired, hepatologists should be aware of this diagnosis in a young patient with ALF.

Autoimmune post-infantile giant cell hepatitis: a case report and review of the literature.

Giant cell hepatitis (GCH) is a rare entity in adults that is characterized by large multinucleated hepatocyte formation and parenchymal inflammation. We present a case of acute liver failure in a 33-year-old woman secondary to autoimmune hepatitis (AIH). A liver biopsy revealed submassive hepatocyte necrosis consistent with GCH. We conducted a literature review of 187 reported cases of post-infantile GCH in adults. AIH was the most commonly reported cause of GCH, but GCH was associated with a wide spectrum of etiologies, including infections, rheumatological diseases, hematological diseases, malignancies, and medications. The severity of disease can range from mild hepatitis to fulminant hepatic failure. The mortality rate among the cases in the literature was 18.82%. GCH is managed by treating the underlying cause, and ribavirin has been proposed as a treatment option for idiopathic GCH. A small number of patients progress to requiring orthotopic liver transplant, but recurrence is possible post-transplant.

Renal tubular injury in hyperbilirubinemia: Bile cast nephropathy.

The toxic renal accumulation of bile pigment sparked clinical intrigue almost a century ago. More recently, however, the identification of bile casts within renal tubules in patients with liver dysfunction has been largely overlooked. We have reviewed the literature, including natural history, pathophysiology, and potential treatment of bile cast nephropathy (BCN). We report two cases of acute kidney injury (AKI) associated with acute-on-chronic liver failure in which prolonged hyperbilirubinemia and bile cast identification on renal biopsy evoked the diagnosis of BCN.

Non-alcoholic steatohepatitis in liver transplant recipients diagnosed by serum cytokeratin 18 and transient elastography: A prospective study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) seem common after liver transplantation. AIM: To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients, namely controlled attenuation parameter (CAP) and the serum biomarker cytokeratin 18 (CK-18). We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology. METHODS: We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018. Serial measurements of CK-18 and CAP were recorded. NAFLD and NASH were diagnosed by CAP ≥ 270 dB/m, and a combination of CAP ≥ 270 dB/m with CK-18 > 130.5 U/L, respectively. Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards. RESULTS: Overall, 40 liver transplant recipients (mean age 57 years; 70% males) were included. During a median follow-up of 16.8 mo (interquartile range 15.6-18.0), 63.0% and 48.5% of patients developed NAFLD and NASH, respectively. On multivariable analysis, after adjusting for sex and alanine aminotransferase, body mass index was an independent predictor of development of NAFLD [adjusted hazard ratio (aHR): 1.21, 95% confidence interval (CI): 1.04-1.41; P = 0.01] and NASH (aHR: 1.26, 95%CI: 1.06-1.49; P < 0.01). Compared to liver histology, CAP had a 76% accuracy to diagnose NAFLD, while the accuracy of CAP plus CK-18 to diagnose NASH was 82%. CONCLUSION: NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo. Close follow-up and nutritional counselling should be planned in overweight patients.

Prevalence and predictors of nonalcoholic fatty liver disease in South Asian women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary disease (PCOS) may be a risk factor for nonalcoholic fatty liver disease (NAFLD) due to common pathogenetic pathways, including insulin resistance and obesity. Both PCOS and NAFLD are more severe in South Asian women. Data on NAFLD in South Asian women with PCOS are lacking. AIM: To investigate prevalence and predictors of NAFLD and liver fibrosis in PCOS patients from South Asia. METHODS: We conducted an observational routine screening program by means of transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD was defined as CAP ≥ 288 decibels per meter. Significant liver fibrosis (stage 2 and higher out of 4) was defined as TE measurement ≥ 8.0 kilopascals. Elevated alanine aminotransferase (ALT) was defined as ALT > 24 IU/L, as per upper limit of normal reported in South Asian women. Biochemical hyperandrogenism was defined as free androgen index > 5. Predictors of NAFLD were determined by logistic regression analysis. RESULTS: 101 PCOS patients (mean age 36.3 years) with no significant alcohol intake or viral hepatitis were included. Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%, respectively. Elevated ALT was observed in 40% and 11.5% of patients with and without NAFLD, respectively. After adjusting for duration of PCOS and insulin resistance measured by homeostasis model for assessment of insulin resistance, independent predictors of NAFLD were higher body mass index [adjusted odds ratio (aOR) 1.30, 95% confidence interval (CI): 1.13-1.52], hyperandrogenism (aOR: 5.32, 95%CI: 1.56-18.17) and elevated ALT (aOR: 3.54, 95%CI: 1.10-11.47). Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD (0.31 ± 0.11 vs 0.26 ± 0.13). CONCLUSION: Despite their young age, NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher body mass index and hyperandrogenism. Non-invasive screening strategies could help early diagnosis and initiation of interventions, including counselling on weight loss, cardiovascular risk stratification and linkage to hepatology care where appropriate.

Prevalence, Predictors, and Severity of Lean Nonalcoholic Fatty Liver Disease in Patients Living With Human Immunodeficiency Virus.

BACKGROUND: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in people living with human immunodeficiency virus (HIV). NAFLD is associated with obesity; however, it can occur in normoweight (lean) patients. We aimed to investigate lean NAFLD in patients living with HIV. METHODS: We included patients living with HIV mono-infection from 3 prospective cohorts. NAFLD was diagnosed by transient elastography (TE) and defined as controlled attenuation parameter ≥248 dB/m, in absence of alcohol abuse. Lean NAFLD was defined when a body mass index was <25 kg/m2. Significant liver fibrosis was defined as TE ≥7.1 kPa. The presence of diabetes, hypertension, or hyperlipidemia defined metabolically abnormal patients. RESULTS: We included 1511 patients, of whom 57.4% were lean. The prevalence of lean NAFLD patients in the whole cohort was 13.9%. NAFLD affected 24.2% of lean patients. The proportions of lean NAFLD patients who were metabolically abnormal or had elevated alanine aminotransferase (ALT) were higher than among those who were lean patients without NAFLD (61.9% vs 48.9% and 36.7% vs 24.2%, respectively). Lean NAFLD patients had a higher prevalence of significant liver fibrosis than lean patients without NAFLD (15.7% vs 7.6%, respectively). After adjusting for sex, ethnicity, hypertension, CD4 cell count, nadir CD4 <200µ/L, and time since HIV diagnosis, predictors of NAFLD in lean patients were age (adjusted OR [aOR], 1.29; 95% confidence interval [CI], 1.04-1.59), high triglycerides (aOR, 1.34; 95% CI, 1.11-1.63), and high ALT (aOR, 1.15; 95% CI, 1.05-1.26), while a high level of high-density lipoprotein cholesterol was protective (aOR, 0.45; 95% CI, .26-.77). CONCLUSIONS: NAFLD affects 1 in 4 lean patients living with HIV mono-infection. Investigations for NAFLD should be proposed in older patients with dyslipidemia and elevated ALT, even if normoweight.

Nonalcoholic Fatty Liver Disease and the Development of Metabolic Comorbid Conditions in Patients With Human Immunodeficiency Virus Infection.

BACKGROUND: Cardiovascular and liver disease are main causes of death in people with human immunodeficiency virus (HIV) (PWH). In HIV-uninfected patients, nonalcoholic fatty liver disease (NAFLD) is associated with incident metabolic complications. We investigated the effect of NAFLD on development of metabolic comorbid conditions in PWH. METHODS: We included PWH undergoing a screening program for NAFLD using transient elastography. NAFLD was defined as a controlled attenuation parameter ≥248 dB/m with exclusion of other liver diseases. Incident diabetes, hypertension, dyslipidemia, and chronic kidney disease were investigated using survival analysis and Cox proportional hazards. RESULTS: The study included 485 HIV-monoinfected patients. During a median follow-up of 40.1 months (interquartile range, 26.5-50.7 months), patients with NAFLD had higher incidences of diabetes (4.74 [95% confidence interval, 3.09-7.27] vs 0.87 [.42-1.83] per 100 person-years) and dyslipidemia (8.16 [5.42-12.27] vs 3.99 [2.67-5.95] per 100 person-years) than those without NAFLD. With multivariable analysis, NAFLD was an independent predictor of diabetes (adjusted hazard ratio, 5.13; 95% confidence interval, 2.14-12.31) and dyslipidemia (2.35; 1.34-4.14) development. CONCLUSIONS: HIV-monoinfected patients with NAFLD are at higher risk of incident diabetes and dyslipidemia. Early referral strategies and timely management of metabolic risk may improve outcomes.

Optimizing patients with non-alcoholic fatty liver disease pre-transplant.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Non-alcoholic steatohepatitis (NASH), which is the progressive counterpart of the disease, is becoming the leading indication for liver transplantation in North America. Owing to the lack of symptoms, NASH is often an incidental diagnosis, resulting in a significant proportion of patients being diagnosed when advanced liver disease has already developed. NAFLD has recently been characterized as the hepatic manifestation of metabolic syndrome. Consequently, it is a multisystem disease that often co-exists with several other conditions, such as obesity, diabetes, cardiovascular diseases, and extra-hepatic malignancy, which have an impact on selection of transplant recipients. The complexity of diagnostic approach, need for multidisciplinary clinical management, and lack of a specific treatment further complicate the picture of this extremely prevalent liver condition. NAFLD patients with advanced liver disease should be considered for early referral to liver transplant clinics for careful metabolic and cardiovascular risk stratification because they have worse survival rates after liver transplantation than other patients with chronic liver disease. Early referral will also facilitate optimization of metabolic comorbidities before proceeding with transplantation. This review provides an overview of strategies to identify patients with advanced NAFLD, with an emphasis on the management of associated comorbidities and optimal timing of pre-transplant evaluation. Other topics that have been shown to affect recipient optimization, such as the role of lifestyle changes and bariatric surgery in the management of obesity, as well as sarcopenia in decompensated NASH-related cirrhosis, are addressed.

Vitamin E is an effective treatment for nonalcoholic steatohepatitis in HIV mono-infected patients.

OBJECTIVE: HIV-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among HIV-infected patients remain unknown. DESIGN: Single-centre, phase IV, open-label, single arm clinical trial. METHODS: HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) at least 248 dB/m and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) greater than 130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks postdiscontinuation. Generalized linear mixed effects models were used to evaluate changes in alanine aminotransferase (ALT), CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pretreatment trends. RESULTS: A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared with baseline, 24 weeks of vitamin E treatment improved ALT [-27 units/l; 95% confidence interval (CI) -37 to -17], CAP scores (-22 dB/m; 95% CI -42 to -1) and CK-18 (-123 units/l; 95% CI -201 to -46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up. CONCLUSION: In this first clinical trial, we showed that vitamin E is an effective and well tolerated treatment for NASH in HIV-infected patients.

Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown. METHODS: HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status. RESULTS: A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%). CONCLUSIONS: HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.

Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient elastography in HIV mono-infection.

BACKGROUND AND AIM: HIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools. METHODS: HIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE) with controlled attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP ≥248 dB/m) and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis. RESULTS: 202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%), insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR) (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01-1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50-3.79; p<0.001) were independent predictors of NASH. CONCLUSIONS: NASH, diagnosed by a non-invasive diagnostic approach employing CK-18 and TE with CAP, is common in unselected HIV mono-infected individuals, particularly in the presence of insulin resistance and elevated ALT.

Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

BACKGROUND & AIMS: Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. METHODS: The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. RESULTS: A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. CONCLUSION: HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.