https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.25762

The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

SUMMARY Background Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years. Aim To review epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years. Methods An in-depth search of PubMed (1980–2010) was based on five search terms: ‘nonalcoholic fatty liver disease’ OR ‘non-alcoholic steatohepatitis’ OR ‘fatty liver’ OR ‘steatosis’ AND ‘incidence’ [MeSH Terms] OR ‘prevalence’ [MeSH Terms] OR ‘natural history’. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2036.2011.04724.x

Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults.

/pdf/nccn-clinical-practice-guidelines-in-oncology-hepatobiliary-1kpacqqvi8.pdf

NCCN clinical practice guidelines in oncology: hepatobiliary cancers.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

https://www.gastrojournal.org/article/S0016-5085%2812%2900494-5/pdf

The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology

There have been few reports on hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) and the natural history of NASH. Accordingly, we assessed the clinical features of HCC in NASH, the risk factors for HCC, and natural history of NASH with advanced fibrosis. There were 34 NASH patients with HCC and 348 NASH patients without HCC. To clarify the clinical features of NASH patients with HCC and to determine the risk factors for HCC, we compared NASH patients with HCC with those without HCC. Univariate and multivariate logistic regression models were used for statistical analysis. A prospective cohort study of the outcomes of 137 NASH with advanced fibrosis was started in 1990. The impact of baseline risk factors on the development of HCC and survival was evaluated by Cox regression analysis. In total, 88% of patients with HCC had advanced fibrosis, with a median age of 70 years. Older age, low level of AST, low grade of histological activity, and advanced stage of fibrosis were risk factors for HCC. A prospective cohort study showed that the 5-year cumulative incidence of HCC was 7.6%, and the 5-year survival rate was 82.8%. HCC was the leading cause of death. The present study confirmed that older age and advanced fibrosis were important risk factors for HCC, and that HCC was the major cause of mortality in NASH patients with advanced fibrosis. Regular screening for HCC is thus extremely important for NASH patients with advanced fibrosis.

Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis

Background and Aim:  Ethnic differences in non-alcoholic steatohepatitis (NASH) are well-documented, but there has been no study on the prognosis of Japanese NASH patients with cirrhosis. Accordingly, we compared cirrhotic NASH with liver cirrhosis caused by chronic hepatitis C (LC-C) to clarify its clinical features and define the risk factors for death.



Methods:  A prospective evaluation of the outcomes of NASH patients with severe fibrosis was started in 1990. Data on age- and sex-matched patients with biopsy-proven LC-C were collected retrospectively and used as the control.



Results:  There were 68 patients with cirrhotic NASH and 69 with LC-C. The Child–Turcotte–Pugh (CTP) class was similar in these two groups. Although the outcome of the NASH group was better than that of the LC-C group, cirrhotic NASH followed a similar course to that of LC-C; that is, complications of cirrhosis developed, including hepatocellular carcinoma (HCC; the 5-year HCC rate was 11.3% for NASH and 30.5% for HCV) and death (the 5-year survival rates were 75.2% and 73.8%, respectively). HCC was the leading cause of death in both groups (NASH, 47%; HCV, 68%). The occurrence of HCC and the CTP class were significant risk factors for mortality in NASH patients according to a multivariate analysis (HCC: hazard ratio [HR] 7.96, 95% confidence interval [CI] 2.45–25.88, CTP class A: HR 0.17, 95% CI 0.06–0.50).



Conclusion:  In conclusion, the present study confirmed that cirrhotic NASH has a similar course to LC-C. The occurrence of HCC was the strongest predictor of mortality in the NASH groups. These findings may be helpful when deciding on therapeutic interventions for NASH and also for the daily management of these patients.

Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C.

Background and Aim:  Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver disease from simple steatosis to cirrhosis. Therefore, markers for predicting NAFLD with advanced fibrosis are needed. The aim of this study was to establish non-invasive predictive markers of liver fibrosis in NAFLD.



Methods:  One hundred and forty-eight patients were diagnosed as having biopsy-proven NAFLD. In order to separately identify severe fibrosis (bridging fibrosis plus cirrhosis) and cirrhosis, the patients were analyzed twice: first, as mild fibrosis versus severe fibrosis; and second, as non-cirrhosis versus cirrhosis. Univariate and multivariate analyses were conducted. The diagnostic ability to detect severe fibrosis and cirrhosis was assessed by the area under the receiver operating characteristic curve. The cut-off values of serum markers to detect severe fibrosis and cirrhosis were determined.



Results:  Hyaluronic acid was selected as a predictive marker for severe fibrosis. A cut-off value of 42 ng/mL of hyaluronic acid had a 100% predictive value for patients free of severe fibrosis and was associated with an optimal combination of sensitivity (100%, 95% confidence interval [CI] 90–100%) and specificity (89%, 95%CI 80–94%). The platelet count was found to be an independent predictor of cirrhosis. A cut-off value of 16 × 104/µL for the platelet count was associated with an optimal combination of sensitivity (100%, 95%CI 82–100%) and specificity (95%, 95%CI 90–98%).



Conclusions:  Hyaluronic acid levels can accurately identify NAFLD patients with severe fibrosis, and the platelet count can identify NAFLD patients with cirrhosis. Thus, these markers offer a good guideline for the assessment of hepatic fibrosis in the many patients with NAFLD.

Hyaluronic acid levels can predict severe fibrosis and platelet counts can predict cirrhosis in patients with nonalcoholic fatty liver disease

Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by the histological features of steatohepatitis in the absence of significant alcohol consumption. The natural history of NASH is poorly defined. Here we report our experience with a patient to illustrate the clinical course of cirrhotic NASH. A 67-year-old woman was admitted with hematemesis due to the rupture of esophageal varices. Her varices were treated by endoscopic ligation and endoscopic sclerotherapy. Her medical history was unremarkable. Both the patient and her family members were asked about alcohol intake several times during her illness, but all of them denied a history of alcohol intake. She had insulin resistance, as determined by homeostasis model assessment. Serological tests for viral hepatitis were all negative. Viral hepatitis, autoimmune liver disease, iron overload, and metabolic liver disorders were all excluded. Imaging tests failed to reveal any steatosis, because of the presence of severe fibrosis. Liver biopsy showed moderate steatosis, moderate inflammation, ballooning degeneration, and Mallory bodies. We diagnosed NASH associated with cirrhosis based on the clinicopathological features. Almost 2 years later, she developed hepatocellular carcinoma (HCC) and she died of multiple HCCs. At autopsy, tumor invasion was seen throughout liver segment 8. The noncancerous liver showed burnt-out NASH; the steatosis, necroinflammation, ballooning degeneration, and Mallory bodies had all disappeared. In Japan, the prevalence of nonalcoholic fatty liver disease will increase as obesity has been increasing, so it is important to understand how to diagnose NASH. When a patient has NASH, careful follow-up should be performed.

Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH.

Objective The present study was performed to clarify the ability of ultrasonography (US) and computed tomography (CT) to detect steatosis and advanced fibrosis in nonalcoholic steatohepatitis (NASH) patients, and to assess the influence of steatosis, fibrosis, and obesity on the radiological detection of steatosis and advanced fibrosis. Methods One hundred and eighteen biopsy proven NASH patients underwent US and CT within 6 months before or after biopsy. The ability of US and CT to detect histological steatosis and advanced fibrosis was assessed. To evaluate whether fibrosis and obesity interfered with the detection of moderate to severe histological steatosis by US and CT, we analyzed 88 NASH patients with moderate to severe steatosis. To evaluate interference with the detection of advanced fibrosis by steatosis and obesity, we analyzed 59 NASH patients with advanced fibrosis. Results The sensitivity of US for detecting moderate to severe histological steatosis in patients with mild histological fibrosis was 100%, but this was reduced to 77.8% in patients with advanced histological fibrosis (p=0.001). The sensitivity of CT was 69.8% in patients with mild histological fibrosis and 48.9% in those with advanced histological fibrosis (p=0.047). The sensitivity of US and CT for moderate to severe histological steatosis was similar in each body mass index group. The sensitivity for detecting advanced fibrosis was markedly decreased by severe steatosis and obesity in the case of both US and CT. Conclusion If we are aware of these disadvantages of US and CT, it is useful for diagnosing steatosis and fibrosis in NAFLD patients.

Satoru Yatsuji

Papers

Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis

Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C.

Hyaluronic acid levels can predict severe fibrosis and platelet counts can predict cirrhosis in patients with nonalcoholic fatty liver disease

Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH.

Imaging of Nonalcoholic Steatohepatitis: Advantages and Pitfalls of Ultrasonography and Computed Tomography