Pathologic Diagnosis of Nonalcoholic Fatty Liver Disease

Context.— Nonalcoholic fatty liver disease (NAFLD) encompasses steatosis and steatohepatitis. The cause may be multifactorial, and diagnosis requires correlation with clinical information and laboratory results. Objective.— To provide an overview of the status of histology diagnosis of steatosis, steatohepatitis, and associated conditions. Data Sources.— A literature search was performed using the PubMed search engine. The terms ‘‘steatosis,'' ‘‘steatohepatitis,'' ‘‘nonalcoholic fatty liver disease (NAFLD),'' ‘‘nonalcoholic steatohepatitis (NASH),'' “alcoholic steatohepatitis (ASH),” ‘‘type 2 diabetes (T2DM),'' “cryptogenic cirrhosis,” “drug-induced liver injury (DILI),” “immune checkpoint inhibitor therapy,” and “COVID-19 and liver” were used. Conclusions.— Nonalcoholic fatty liver disease has become the most common chronic liver disease in the United States. NASH is the progressive form of nonalcoholic fatty liver disease. The hallmarks of steatohepatitis are steatosis, ballooned hepatocytes, and lobular inflammation. NASH and alcoholic steatohepatitis share similar histologic features, but some subtle differences may help their distinction. NASH is commonly seen in patients with metabolic dysfunction but can also be caused by other etiologies. Examples are medications including newly developed immune checkpoint inhibitors and viral infections such as coronavirus disease 2019 (COVID-19). NASH is also a common cause of cryptogenic cirrhosis but can be reversed. The results from recent clinical trials for NASH treatment are promising in reducing the severity of steatosis, ballooning, and fibrosis.

Hepatology Characteristics of patients with cryptogenic cirrhosis: a retrospective study

Backgrounds: This study aimed to achieve a better understanding of the characteristics of patients with cryptogenic cirrhosis (CC). Methods: We retrospectively enrolled 50 patients with CC between January 2018 and December 2020 who were admitted to our hospital. Clinical data, biochemical and immunological parameters, viral markers, imaging findings and liver histopathological features of the patients were analyzed. Results: The percentage of male patients with CC was 58% (29/50). The average age was 54 ± 17 years. Hepatitis C virus (HCV) IgG and hepatitis B surface antigen (HBsAg) were negative for all patients. Hepatitis B virus (HBV) DNA was tested in 68% (34/50) of the patients and the results were undetectable. Ceruloplasmin was detected in 96% (48/50) cases, while 10 cases were Kayser-fleischer ring negative. Immunological tests were conducted in 94% (47/50) of cases, antinuclear antibody (ANA) was elevated in eight cases, whereas anti-mitochondrial antibody (AMA) was elevated in three cases. Liver biopsy was conducted on 11 patients, of which seven were percutaneous and four were transjugular. Immunohistochemistry for HBsAg and HBcAg were all negative. Metavir scoring result showed that six of 11 patients had scores below G2S2. Conclusions: The common laboratory tests especially noninvasive ones were conducted for most of the patients. Diagnosis of CC requires further detection to exclude specific diagnosis such as HBV DNA or intrahepatic covalently closed circular DNA (cccDNA) in HBcAb positive patients, genetic screening of Wilson’s Disease in patients with low ceruloplasmin, etc.

Cryptogenic Cirrhosis may be Nonobese Nonalcoholic Steatohepatitis—Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study

Background As the diagnosis of non-alcoholic steatohepatitis (NASH) has become more accurate, the number of patients with cryptogenic cirrhosis (CC) has decreased. Despite this, there are patients in the liver transplant registry who are currently listed as having CC. Therefore, knowledge of the natural course of CC after liver transplantation (LT) is important. However, the natural course of CC after LT is unknown. We aimed to clarify the natural course post LT for CC and to infer the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of including NASH patients with CC patients, those with obesity (body mass index [BMI] ≥ 25 kg/m2) and type-2 diabetes mellitus or liver steatosis found on pretransplantation images, were excluded. Liver biopsy was performed 1 year after LT, and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of the patients after LT, respectively with a median time to onset of 12 and 27 months, respectively. No other pathological findings could identify the etiology of CC. The BMIs after LT were significantly higher in the steatosis group than in the non-steatosis group (28.5 vs. 22.4 kg/m2; P = 0.002). The mean muscle attenuation (MA) at the time of LT was significantly higher and the postoperative hospitalization period was shorter in the steatosis group than in the non-steatosis group (MA: 33.3 vs. 25.8 Hounsfield unit, P = 0.03; hospitalization: 50 vs. 102 days, P = 0.02). Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years, P = 0.04). Conclusions Despite excluding patients with a history of obesity from our cohort of patients with CC, we observed that patients with CC had a high prevalence of steatosis after LT. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.

Congenital hepatic fibrosis with novel mutations in PKD1 gene masquerading as early cryptogenic cirrhosis: a rare case report

Background Congenital hepatic fibrosis (CHF) is a rare disorder of the porto-biliary system occurring due to the defective remodeling of ductal architecture leading to progressive fibrosis of the portal tract. Though classically, CHF has been reported to be associated with autosomal recessive polycystic kidney disease (ARPKD), there have been only a few reports associating CHF with autosomal dominant polycystic kidney disease (ADPKD). Also, there is a lack of proper sequencing panels and gene database covering CHF-related genes in the medical literature. CHF often presents with features of portal hypertension without overt signs or symptoms of liver disease. However, often due to lack of awareness among radiologists and physicians, such cases might get labeled as early stage of cryptogenic cirrhosis. Case presentation Here, we report a 17-year-old boy who presented with a portal hypertensive bleed. Though initially an early phase of cirrhosis was suspected, no identifiable cause was found. Though he had grade IV esophageal varices, the liver function was absolutely normal with no signs of liver failure. This further leads to subsequent cross-sectional imagings which lead to the diagnosis of CHF. Further genetic analysis revealed it to be a rare case of CHF associated with ADPKD, with some novel mutations in the PKD1 gene. Conclusion CHF is a rare disorder needing a high index of suspicion and awareness. The presence of classic radiological morphological features of left lobe hypertrophy and right lobe atrophy with the tell-tale histopathological findings, fibrous enlargement of the portal tract, and irregularly shaped proliferating bile ducts often clinches the diagnosis.

Portal Vein Aneurysm Treated With Trans-Jugular Intrahepatic Porto-Systemic Shunt

Portal vein aneurysm (PVA) is a rare entity that can lead to hemorrhage or thrombosis. Although there is no standard treatment, most cases can be managed conservatively; intervention is reserved for symptomatic or enlarging aneurysms. For patients who are not surgical candidates due to cirrhosis and portal hypertension, endovascular creation of a trans-jugular intrahepatic porto-systemic shunt (TIPS) is an option to reduce portal venous pressure. This report describes a case of an enlarging PVA successfully treated with TIPS in a patient with cryptogenic cirrhosis.

Bajos niveles de actividad de la lipasa ácida lisosomal y su relación con el desarrollo de la cirrosis de origen criptogénica/NASH: un estudio de cohorte

Introduction and objective. The deficiency of the Lysosomal acid lipase (LAL) activity has been related to cirrhosis due to non-alcoholic steatohepatitis (NASH). Many of the cirrhosis classified as cryptogenic are the evolution of liver disease due to fatty liver. The objective of the present study was to evaluate the lysosomal acid lipase (LAL) activity in the patients with liver cirrhosis of any etiology and establish whether low levels correlate with cryptogenic cirrhosis of origin cryptogenic or NASH. Methods. Was an analytical cohort study including 96 patients with cirrhosis of any etiology for which LAL activity was measured. Results. Fifty-five patients (58%) with cryptogenic cirrhosis or NASH were included and 41 with other etiologies. The fifty-three percent of the total population were women. The severity scores of liver disease were significantly higher in the patients with the cryptogenic cirrhosis or NASH: MELD (11.72 ± 7.3 vs 4,34 ± 5.7; p = 0.001) and Child-Pugh (7.26 ± 3.8 vs 7.26 ± 3.8; p = 0.004). LAL activity was significant lower (202.40 ± 98.8 vs 242.55 ± 121.9; p = 0.04) in the cirrhosis cryptogenic or NASH group. In the multivariate analysis, low LAL activity (< 150 nmol/spot/hour), was correlated with the presence of cryptogenic cirrhosis or NASH. Conclusions. The patients with cryptogenic cirrhosis or NASH have lower levels of LAL activity than those with cirrhosis of other etiologies. LAL activity below 150 nmol/spot/hour is predictive of the cryptogenic cirrhosis or NASH.