Advanced Hepatic Cirrhosis Research Articles

One Family with Cholestasis: The Twisted Road to the Diagnosis of Pfic 3—Three Case Reports

Background and Clinical Significance: Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal recessive disorders consisting of mutations of hepatocyte transporting-system genes involved in bile formation. The exact prevalence remains unknown but is estimated at 1 in 500.000 for PFIC 3, caused by mutations in the ABCB4 gene. We report three cases of PFIC 3 from the patient’s sister, brother, and cousin, diagnosed in our Pediatric Department in 2022–2023. Case Presentation: Case 1: A 10-year-old girl was admitted for jaundice and abdominal pain. She was diagnosed with severely advanced hepatic cirrhosis and massive cholestasis. Genetic testing showed ABCB4 homozygous mutation. She rapidly developed fulminant liver failure, and a living donor liver transplant was performed. Case 2: A 6-year-old brother was previously diagnosed with cholestatic hepatitis of unknown cause back in 2018 and presented with similar features (generalized jaundice, severe pruritus with generalized scratching lesions); symptoms had progressively developed from the first year of life. He also exhibited particular facial features (big forehead, twisted ear lobe, straight nose). He received cadaveric liver transplantation. Case 3: Nephew of first two children, a 3-year-5-month-old boy, was admitted for failure to thrive and a one-year history of jaundice, pruritus, and splenomegaly. He was tested positive for homozygous ABCB4 mutation. He is currently under medical treatment with stable liver function. Conclusions: The clinical significance of this particular homozygous variant identified in ABCB4 in our series of cases (c.2534G>T (p.Gly845Val)) was uncertain up to this case report. The present data provide convincing evidence as to the correlation between this mutation and the clinical phenotype of PFIC 3.

Impact of Weight Loss on Metabolic Dysfunction Associated Steatohepatitis and Hepatic Fibrosis.

This review highlights the impact of weight loss on metabolic dysfunction associated steatotic liver disease (MASLD), formally known as nonalcoholic fatty liver disease (NAFLD), and its progressive form of metabolic dysfunction associated steatohepatitis (MASH), formally known as nonalcoholic steatohepatitis (NASH). The effects of weight loss, as achieved through lifestyle modification, pharmacotherapy, bariatric surgery or endobariatric procedures on MASLD/MASH and hepatic fibrosis are discussed. Although foundational in the treatment of MASLD/MASH, weight loss through life-style modification is challenging for most patients to achieve and sustain long-term. In patients with MASLD/MASH, a multidisciplinary approach may facilitate success with lifestyle modification, individualized consideration of pharmacotherapies and/or surgical approaches that have potential to lend an improvement in MASLD/MASH. Effective and sustained weight loss improves hepatic steatosis, steatohepatitis and potentially hepatic fibrosis. Improvement in hepatic fibrosis can improve patient-related outcomes associated with complications of advanced hepatic fibrosis or cirrhosis in patients with MASLD/MASH. Identifying risk factors that influence MASLD/MASH and early implementation of therapeutic weight loss strategies may improve chronic liver injury and decrease risk for adverse clinical outcomes related to progressive hepatic fibrosis attributable to MASLD/MASH.

A comparative study on the effect of melatonin and orlistat combination versus orlistat alone on high fat diet-induced hepatic changes in the adult male albino rats (a histological and morphometric study)

ABSTRACT Background Nonalcoholic fatty liver disease (NAFLD) is the extremely usual reason of chronic liver disease, extending from simple hepatic steatosis (HS), nonalcoholic steatohepatitis (NASH) to advanced hepatic fibrosis and cirrhosis. Though orlistat is a Food and Drug Administration (FDA) approved drug for long-duration management of obesity, few cases of severe hepatic insult were declared. Melatonin is an efficient antioxidant; it also regulates metabolic processes that lead to fat accumulation and obesity. Aim of the work The current research aimed to compare the impact of orlistat, melatonin, and their combination on the structural changes of the hepatic tissue of adult male albino rats supplied with high fat diet (HFD). Material and methods Thirty adult male albino rats divided into five groups. Liver specimens were divided into two parts. One-half was processed to obtain paraffin blocks, and the other half was processed to obtain semithin sections. Morphometric study and statistical analysis were done. Results Hepatic tissue from the HFD group showed steatosis, ballooning, and inflammation and all these parameters were moderately improved – except for inflammation which worsened with therapy. Combined orlistat and melatonin-treated groups showed marked improvement of all parameters as well as marked improvement in the hepatic fibrosis. Orlistat/Melatonin combination therapy is both safe and effective in comparison to orlistat and melatonin monotherapy.

Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma (HCC) With Single Photon Emission Computed Tomography (SPECT) Functional Treatment Planning in Patients With Advanced Hepatic Cirrhosis

Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma (HCC) With Single Photon Emission Computed Tomography (SPECT) Functional Treatment Planning in Patients With Advanced Hepatic Cirrhosis

THU-389 - The ancestral haplotype HLA-A3 does not influence the likelihood of advanced hepatic fibrosis or cirrhosis in C282Y homozygous hemochromatosis

THU-389 - The ancestral haplotype HLA-A3 does not influence the likelihood of advanced hepatic fibrosis or cirrhosis in C282Y homozygous hemochromatosis

Serum biomarkers predictive of cirrhosis in alcoholic liver disease as an alternative to ARFI-SW elastography.

Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB-4) index are noninvasive biomarkers that evaluate liver stiffness in patients with chronic viral hepatitis and are able to detect advanced hepatic fibrosis and cirrhosis. However, their usefulness in alcoholic liver disease (ALD), when compared with Acoustic Radiation Force Impulse- Shear Wave (ARFI-SW) elastography, is debatable. We sifted the files of all enrolled patients with ALD that were admitted to our Emergency hospital between January 2019 and December 2020. All patients had undergone ARFI-SW elastography, and APRI and FIB-4 scores were calculated. The performance of APRI and FIB-4 scores in the prediction of cirrhotic patients according to ARFI-SW elastography was evaluated. In total, 120 patients with ALD were evaluated. All of them were male and Caucasian, with a mean age of 55.54±12.4 years. The mean ARFI-SW elastography score was 1.57±0.7 m/s, the median APRI score was 0.68 (0.1-11.6) and the median FIB-4 score was 1.8 (0.2-19.4). Stages of liver fibrosis according to ARFI-SW elastography were evaluated as F0-1 in 21 (10.5%), F2 in 35 (26%), F3 in 52 (17.5%), and F4 in 92 (46%) patients. Based on ARFI-SW elastography fibrosis stage classification, we estimated the optimal APRI and FIB-4 scores to predict the presence of liver cirrhosis (F4) by using ROC curve analysis and the Youden index. The optimal APRI score for F4 patients was calculated as >1.52 [area under the curve (AUC) 0.875, 95% CI 0.809-0.919; p<0.001], giving sensitivity (Se) 81.2%, specificity (Sp) 81.4%, positive predictive value (PPV) 76%, and negative predictive value (NPV) 86.1%. The optimal FIB-4 score for F4 patients was calculated as >2.77 (AUC 0.916, 95% CI 0.814-0.922; p<0.001), giving Se 83.8%, Sp 77%, 81.4 77%, and NPV 84.3%. APRI and FIB-4 scores can be used as screening tools in ALD for predicting cirrhosis instead of ARFI-SW elastography measurement, which is neither widely available nor an affordable method. Additional prospective studies are required in the future to confirm this finding.

The ancestral haplotype markers HLA -A3 and B7 do not influence the likelihood of advanced hepatic fibrosis or cirrhosis in HFE hemochromatosis

Advanced hepatic fibrosis occurs in up to 25% of individuals with C282Y homozygous hemochromatosis. Our aim was to determine whether human leukocyte antigen (HLA)-A3 and B7 alleles act as genetic modifiers of the likelihood of advanced hepatic fibrosis. Between 1972 and 2013, 133 HFE C282Y homozygous individuals underwent clinical and biochemical evaluation, HLA typing, liver biopsy for fibrosis staging and phlebotomy treatment. Hepatic fibrosis was graded according to Scheuer as F0–2 (low grade hepatic fibrosis), F3–4 (advanced hepatic fibrosis), and F4 cirrhosis. We analysed associations between the severity of fibrosis and HLA-A3 homozygosity, heterozygosity or absence, with or without the presence of HLA-B7 using categorical analysis. The mean age of HLA-A3 homozygotes (n = 24), heterozygotes (n = 65) and HLA-A3 null individuals (n = 44) was 40 years. There were no significant differences between the groups for mean(± SEM) serum ferritin levels (1320 ± 296, 1217 ± 124, 1348 ± 188 upmug/L), hepatic iron concentration (178 ± 26, 213 ± 22, 199 ± 29 upmumol/g), mobilizable iron stores (9.9 ± 1.5, 9.5 ± 1.5, 11.5 ± 1.7 g iron removed via phlebotomy), frequency of advanced hepatic fibrosis (5/24[12%], 13/63[19%], 10/42[19%]) or cirrhosis (3/24[21%], 12/63[21%], 4/42[24%]), respectively. The presence or absence of HLA-B7 did not influence the outcome. Thus, HLA-A3 and HLA-B7 alleles are not associated with the risk of advanced hepatic fibrosis or cirrhosis in C282Y hemochromatosis.

Clinical value of acoustic radiation force impulse elastography in the prediction of hepatocellular carcinoma in chronic hepatitis C patients

Background and purpose of the studyAcoustic radiation force impulse elastography (ARFI) represents an innovative non-invasive tool for the evaluation of liver fibrosis, cirrhosis, and early identification of neoplastic nodules during the follow-up of cirrhotic patients; however, its diagnostic accuracy in the prediction of hepatocellular carcinoma (HCC) is still controversial.Purpose of the studyTo assess the potential role of ARFI elastography as a non-invasive tool for the prediction of HCC development among chronic hepatitis C (CHC) patients with advanced hepatic fibrosis and liver cirrhosis.MethodsThe present study recruited 440 patients: 349 CHC patients with advanced hepatic fibrosis and cirrhosis and 91 patients with HCC-related hepatitis C virus (HCV). ARFI-imaging of the liver and transient elastography (TE) was carried out in all patients. ARFI imaging indices include the mean shear wave velocity of HCC, peritumoral parenchyma, and hepatic parenchyma in non-HCC patients. The area under the receiver operating characteristic curve (AUROC) and optimal cutoff values were obtained using a receiver operating characteristic curve analysis to assess the diagnostic performance of ARFI elastography in the predication of HCC.ResultsThe mean hepatic shear wave velocities by ARFI elastography of peri-tumoral cirrhotic hepatic parenchyma were significantly higher than in hepatic parenchyma in non-HCC patients (3.09 vs. 2.26 m/s, p <0.001). The AUROC for the identification of HCC was 0.8, 0.76, 0.76, 0.66, 0.72, and 0.7 for hepatic ARFI elastography, TE, fibrosis-4 score (FIB-4), AST to Platelet Ratio Index (APRI), AST/ALT ratio (AAR), and Age platelets index (API), respectively. Moreover, univariate regression analysis revealed that hepatic ARFI has the highest odd ratio in the prediction of HCC.ConclusionARFI elastography had a superior diagnostic performance in the prediction of HCC compared to TE and non-invasive markers in CHC patients with advanced fibrosis and cirrhosis, thus putting such patients on the top of the HCC screening list.

Regulatory Role of Ribonucleotide Reductase Subunit M2 in Hepatocyte Growth and Pathogenesis of Hepatitis C Virus.

Hepatitis C virus (HCV) frequently causes chronic infection in the human liver, which may progress to advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. HCV primarily infects highly differentiated quiescent hepatocytes and can modulate cell cycle-regulatory genes and proliferation pathways, which ultimately contribute to persistent infection and pathogenesis. On the other hand, several studies have shown differential regulation of HCV RNA and viral protein expression levels, depending on the proliferation state of hepatocytes and the phase of the cell cycle. HCV typically requires factors provided by host cells for efficient and persistent viral replication. Previously, we found that HCV infection upregulates the expression of ribonucleotide reductase subunit M2 (RRM2) in quiescent hepatocytes. RRM2 is a rate-limiting protein that catalyzes de novo synthesis of deoxyribonucleotide triphosphates, and its expression is highly regulated during various phases of the cell cycle. RRM2 functions as a pro-viral factor essential for HCV RNA synthesis, but its functional role in HCV-induced liver diseases remains unknown. Here, we present a comprehensive review of the role of the hepatocyte cell cycle, in correlation with RRM2 expression, in the regulation of HCV replication. We also discuss the potential relevance of this protein in the pathogenesis of HCV, particularly in the development of hepatocellular carcinoma.

Liver Function Preservation and Outcome after SBRT with Functional Treatment Planning in Patients with HCC and Advanced Hepatic Cirrhosis: From Nuclear Medicine to MRI-Based Functional Treatment Planning Platform

Liver Function Preservation and Outcome after SBRT with Functional Treatment Planning in Patients with HCC and Advanced Hepatic Cirrhosis: From Nuclear Medicine to MRI-Based Functional Treatment Planning Platform

Association between hepatic steatosis and fibrosis indices and dietary habits, physical activity, and quality of life

Association between hepatic steatosis and fibrosis indices and dietary habits, physical activity, and quality of life

Development and validation of an ensemble machine learning framework for detection of all-cause advanced hepatic fibrosis: a retrospective cohort study

Development and validation of an ensemble machine learning framework for detection of all-cause advanced hepatic fibrosis: a retrospective cohort study

Stereotactic body radiotherapy (SBRT) with functional treatment planning in patients with hepatocellular carcinoma (HCC) and advanced hepatic cirrhosis: Survival outcomes and toxicity.

460 Background: To evaluate outcomes and dosimetric parameters of ablative stereotactic body radiotherapy (SBRT) with functional treatment planning for localized hepatocellular carcinoma (HCC) in patients with Child-Pugh B (CP-B) hepatic cirrhosis. Methods: Liver SPECT with 99mTc-sulfur colloid was co-registered to 3D-CT for identification and avoidance of functional hepatic parenchyma during SBRT in patients with advanced cirrhosis. Functional liver volumes (FLV-SPECT) were compared to anatomical liver volumes, as were dosimetric parameters when radiation dose constraints were adapted exclusively to FLV-SPECT. Hepatic function, toxicity, and radiographic response were documented every 4–6 months following SBRT. Results: With a median follow-up of 25 months 37 patients (48 lesions treated) with CP-B cirrhosis received SBRT to a median dose 48 Gy (4–5 fractions). FLV-SPECT volume loss (509 cc or 41.3%, p &lt; 0.001) was observed in all patients, while the functional and anatomical liver volumes matched well in a control group of non-cirrhotic/non-HCC patients. While tumors received ablative irradiation, mean dose to FLV-SPECT was maintained at 1.3 – 16 Gy (median 9.17 Gy), well below the liver threshold tolerance to radiation. Seventeen patients successfully completed liver transplant at a median time to transplant of 6.5 months. The dropout rate from the transplant list was 9 % with intrahepatic progression outside treated tumors. Eight of 10 patients with intrahepatic progression received additional SBRT during follow-up. Overall 2-year survival rate was 65% with no incidence of RILD or CP class migration from B to C was observed at 6+ months post SBRT. Two patients completed liver SBRT on a hybrid linear accelerator combined with MRI scanner (Unity MR-Linac, Elekta) utilizing Super-Paramagnetic Iron Oxide (SPIO) nanoparticle agent as an alternative contrast media for functionally active liver parenchyma. Prolonged SPIO-contrast retention also allowed per fraction treatment plan adaptation and enhanced tumor imaging. Conclusions: SBRT planning with 99mTc sulfur colloid SPECT allows identification and conformal avoidance of residual functionally active hepatic parenchyma in patients with CP-B cirrhosis. We report high local control and low toxicity leading to satisfactory pre- and post-liver transplant outcomes. Prospective clinical trial investigating MRI-SPIO functional treatment planning for liver SBRT is ongoing at our institution.

Hepatorenal syndrome: pathophysiology and evidence-based management update.

Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.

1-year outcomes for lung transplantation recipients with non-alcoholic fatty liver disease.

Advanced hepatic fibrosis and cirrhosis are absolute contraindications to lung transplantation. [ 1] However, whether fatty liver disease with mild–moderate fibrosis contributes to increased adverse outcomes post-lung transplantation remains unknown. We present a retrospective analysis of patients transplanted at Brigham and Women's Hospital between 2015 and 2017 to identify whether patients with mild–moderate non-alcoholic fatty liver disease (NAFLD) experience increased short-term complications compared to patients with normal liver architecture. Patients with advanced (F3–F4) fibrosis and/or cirrhosis were considered non-suitable transplant candidates, a priori. This study was powered for a difference in index hospital-free days within the first 30 days of 25% (α=0.05, β=0.8). Secondary outcomes included index intensive care unit (ICU)-free days within the first 10 days post-transplant, perioperative blood product transfusion, incidence of index hospitalisation arrhythmias and delirium, need for insulin on discharge post-transplant, tacrolimus dose required to maintain a trough of 8–12 ng·mL−1 at index hospital discharge, and 1-year post-transplant incidence of insulin-dependent diabetes, acute kidney injury, acute cellular rejection, unplanned hospital readmissions and infection. 150 patients underwent lung transplantation between 2015 and 2017 and were included in the analysis; of these patients 40 (27%) had evidence of NAFLD. Median index hospital-free days for patients with NAFLD were non-inferior to those without (16 days, IQR 10.5–19.5 versus 12 days, IQR 0–18.0, p=0.03). Regarding secondary outcomes, both index hospitalisation and 1-year outcomes were non-inferior between patients with NAFLD and those with normal liver architecture. This study demonstrates that mild–moderate severity NAFLD may not be a contraindication to lung transplantation.

Allele-specific variation at APOE increases nonalcoholic fatty liver disease and obesity but decreases risk of Alzheimer's disease and myocardial infarction.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P < 5.30 × 10-7); including a novel signal near TOMM40/APOE. Joint analysis of TOMM40/APOE variants revealed the TOMM40 signal was attributed to APOE rs429358-T; APOE rs7412 was not associated with liver attenuation. Moreover, rs429358-T was associated with higher serum alanine aminotransferase, liver steatosis, cirrhosis, triglycerides and obesity; as well as, lower cholesterol and decreased risk of myocardial infarction and Alzheimer's disease (AD) in phenome-wide association analyses in the Michigan Genomics Initiative, United Kingdom Biobank and/or public datasets. These results implicate APOE in imaging-based identification of NAFLD. This association may or may not translate to nonalcoholic steatohepatitis; however, these results indicate a significant association with advanced liver disease and hepatic cirrhosis. These findings highlight allelic heterogeneity at the APOE locus and demonstrate an inverse link between NAFLD and AD at the exome level in the largest analysis to date.

Assesmentof Fibro Q test, AAR &amp; APRI indices as markers of fibrosis in chronic liver disease

Chronic liver disease can vary from mild hepatic inflammation without fibrosis to advanced hepatic fibrosis and cirrhosis. The use of ultrasound for the confirmation of complications during biopsy procedures increases the cost of treatment and may also increase the duration of hospitalization. Fibro Q test (FQT), Aspartate amino transferase – Alanine amino transferase ratio (AAR) &amp; Aspartate amino transferase- platelet ratio index (APRI) are the three non-invasive and simple indices proposed for assessing fibrosis in CLD. To know the efficacy of the indices- Fibro Q test, AAR, APRI as markers of Fibrosis in CLD. To know which among these indices would be the high sensitive marker of liver fibrosis.This study includes 60 subjects, out of which 30 were clinically diagnosed as CLD and were confirmed by abdominal ultrasound and 30 were age matched healthy controls. Fibro Q, AAR &amp; APRI were significantly increased in cases compared to controls. The increase in Fibro Q test in cases was highly significant (p-0.0001) when compared to controls.Fibro Q test, AAR &amp; APRIindicesare efficient markers to evaluate liver fibrosis in CLD patients. Fibro Q, a novel non-invasive test, is highly sensitive marker than AAR &amp; APRI.

Surgical Resection of Hepatocellular Carcinoma in Compensated Cirrhotic Liver: The Benefits and Selection Criteria

Background: Hepatocellular carcinoma (HCC) represents a fifth of common malignancies, with an annual diagnosis of 750,000 new cases. It is the third cause of cancer deaths worldwide. The cirrhotic liver is a leading cause of HCC with the annual conversion rate to HCC in the range of 2–6 %. The underlying liver cirrhosis limits certain treatment modalities that potentially further aggravates liver dysfunction. Over the past decade, there were substantial improvements in the HCC resection techniques that has resulted in the reduction of operative mortality. This allowed doing major hepatectomy in cirrhotic patients who are suitable for liver transplantation but lacking availability of cadaveric or living donors. Also, patients who have multi-focal HCC underlying cirrhosis which render them unsuitable for liver transplantation due to its extension beyond Milan criteria. Objective: The objective of this study was to assess the benefits and selection criteria of HCC surgical resection within child–Turcotte–Pugh score (CTP) A and B liver cirrhosis to achieve the best surgical outcomes. Methods: We performed a literature search within English written trials using PubMed and MEDLINE reviews databases from 1986 to 2017. One hundred fifty studies are included in this review evaluating various parameters including HCC and compensated cirrhosis prevalence, pathogenesis, clinical presentation, and diagnostic methods. Furthermore, we have compared oncological hepatic resection with other modalities like transarterial chemoembolization, liver transplantation, embolization of the portal vein, laparoscopic hepatic resection, and ALPPS technique. Principles of surgical hepatectomy and postoperative complications are also presented in this review. Conclusion: This review has demonstrated that hepatic cirrhosis complicated by portal hypertension is not an absolute contraindication for HCC resection. Furthermore, elective surgery must not be directed exclusively to CTP A cirrhosis but it can be applied to highly selected patients who had suffered from advanced hepatic cirrhosis. If multifocal HCC underlying hepatic cirrhosis was unsuitable for liver transplantation, hepatectomy can be carried out to increase the tumor cure chances, prevent it's recurrences, and lead to significant survival rate improvement. The degree of cirrhosis significantly affects the decision of primary hepatic carcinoma treatment and it's prognosis. The interdisciplinary assessment of liver function by surgeons, hepatologists, anesthesiologists, and specialists of critical care are essential for maximum critical stabilization of the patients. Keywords: Child-Turcotte-Pugh score; hepatocellular carcinoma; hepatectomy; liver cirrhosis; portal hypertension

Clinical prediction of HBV and HCV related hepatic fibrosis using machine learning.

Clinical prediction of HBV and HCV related hepatic fibrosis using machine learning.

Autoimmune Hepatitis in the Elderly: Diagnosis and Pharmacologic Management.

Autoimmune hepatitis (AIH) may present as acute or chronic hepatitis in the elderly. Advanced hepatic fibrosis and cirrhosis are common on first presentation in this population. In this review, we discuss the presentation, approach to diagnosis and management of AIH in the elderly. As polypharmacy is common in the elderly, careful medication use history is essential for detecting drug-induced AIH-like hepatitis. Steroid-sparing or minimizing therapeutic regimens are preferred to treat AIH in the elderly. For the purpose of induction, budesonide or lower dose prednisone in combination with azathioprine (AZA) regimens are preferred over high-dose prednisone monotherapy due to the higher risk of side effects of the later in the elderly. The goal of maintenance therapy should be to achieve full biochemical and histologic remission. Bone density monitoring and interventions to prevent steroid-related bone disease should be implemented throughout the course of the disease. Liver transplantation should be considered in the elderly patient with liver failure or early hepatocellular carcinoma if there are no significant comorbidities or compromise in functional status.