https://www.gastrojournal.org/article/S0016-5085(04)01593-8/pdf

Hepatocellular carcinoma in cirrhosis: incidence and risk factors.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2003.50193

Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders. An expansion of Porphyromonadaceae in the gut is linked to the pathogenesis and progression of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in the mouse. Using a mouse model, Richard Flavell and co-workers study the inflammatory processes associated with progression from non-alcoholic fatty liver disease — the leading cause of chronic liver disease in developed countries — to the more severe non-alcoholic steatohepatitis, which often leads to cirrhosis and hepatocellular carcinoma. They find that alterations of the intestinal microbiota associated with the NLRP6 and NLRP3 inflammasomes enhance disease in mice with diet-induced non-alcoholic fatty liver syndrome. These findings highlight the pivotal role of the microbiota in the development of autoinflammatory and metabolic disorders, and point to the manipulation of host–microflora interactions as a focus for new therapies.

/pdf/inflammasome-mediated-dysbiosis-regulates-progression-of-yllchopepd.pdf

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.510300604

Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis

AGA technical review on nonalcoholic fatty liver disease

The aim of the present was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population Among patients with cirrhosis, prognosis was dependent upon Child classification (P = 0001) Patients with alcoholic cirrhosis and fatty liver disease were younger (P = 001) and had a lower life expectancy than patients with other causes of chronic liver disease (P = 0004) Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population In patients with alpha 1-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P = 001) For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and alpha 1-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment In patients with hereditary liver disease, additional viral infection of alcohol abuse lead to a significant deterioration of life expectancy Patients with alcoholic chronic liver disease have the poorest prognosis

Prognosis and life expectancy in chronic liver disease.

Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination

▪Objective:To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) α1-antitrypsin deficiency and to assess the presence of other poss...

High Prevalence of Viral Infection in Adults with Homozygous and Heterozygous Alpha1-Antitrypsin Deficiency and Chronic Liver Disease

Prognosis in nonalcoholic steatohepatitis.

The importance of sexual transmission in the epidemiology of hepatitis C virus (HCV) infection is still controversial. To assess the risk of heterosexual HCV transmission, we examined eighty patients with chronic HCV-associated liver disease and their spouses in a cross-sectional clinical and serological cohort study. Serum samples from index patients and their spouses were assayed for HCV antibodies and HCV RNA. In the couples positive for both, further HCV genotyping was done. A questionnaire addressing points such as additional risk factors for HCV infection, sexual behaviour or duration of partnership was completed by all couples. HCV antibodies were detected in four (5%) spouses, of whom three (4%) were also positive for HCV-RNA. HCV genotyping revealed concordance (genotype 1) in two couples, indicating a risk of interspousal HCV transmission of 2.5%. Spouses of patients with HCV viraemia and chronic liver disease have a low risk for acquiring HCV. Even long-term spouses seem not to be at increased risk. We therefore suggest that the risk of HCV transmission between monogamous sex partners does not depend on the duration of sexual exposure.

A. Propst

Papers

Prognosis and life expectancy in chronic liver disease.

Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination

High Prevalence of Viral Infection in Adults with Homozygous and Heterozygous Alpha1-Antitrypsin Deficiency and Chronic Liver Disease

Prognosis in nonalcoholic steatohepatitis.

Lack of evidence for the heterosexual transmission of hepatitis C.