Our data suggest M30 as highly specific marker of liver apoptosis both in ALD and NAFLD. In addition, hepatocellular apoptosis, as determined by M30 levels, occurs during alcohol withdrawal, and survival data point toward a novel underestimated role of apoptosis in patients with ALD. (Hepatology 2017;66:96-107).

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PNPLA3 GG genotype has been identified as important progression factor in patients with ALD and NAFLD. Since PNPLA3 function remains poorly understood, we here studied genotype distribution and various noninvasive, serum and molecular markers of liver damage and steatosis in 521 heavy drinkers (mean alcohol consumption 191.2 g per day) prior and after alcohol withdrawal. Liver histology was obtained in 80 patients and allowed additional immunostaining for lipid droplet (LD)-associated proteins (N = 47) and expression of mRNA transcripts (N = 24). PNPLA3 GG carriers (8.2%) drunk significantly less high percentage beverages (23% vs 55%, p < 0.001) and showed no increased weight, BMI or diabetes. Liver stiffness (LS) was significantly elevated in G carriers (median 18 vs. 11 kPa) and correlated with histological signs of fibrosis (r = 0.8) and liver damage (ballooning, r = 0.7), but not with steatosis. In CG carrier, LS decreased significantly from 17.6 to 12.7 but less in GG carriers. Moreover, hepatic fat content as quantified by CAP did not significantly differ between the groups and decreased equally by 30 dB/m. On the molecular level, key molecules, important for lipolysis and flow of free fatty acids to the liver, were drastically reduced in G allele carriers. These included the liver-synthesized serum ApoA1, the LD-associated protein perilipin5 and the recently identified hepatoprotective transcriptional cofactor transducin beta-like-related 1 (TBLR1). Conclusion: In heavy drinkers, PNPLA3 GG primarily correlates with hepatocyte damage resulting in a reversible, inflammationassociated increase of LS and the suppression of key molecules that are important for lipolysis and hepatocellular fat mobilization.

Promoted by the decoding of the human genome as part of the human genome project, individualised therapy approaches have become a realistic perspective for therapies that are more effective, less prone to side effects and economically reasonable. This also applies to chronic liver disease. With the aim not only to expand the current knowledge base through basic research on the underlying disease processes and treatment options but also to identify and characterise biomarkers, the creation of genetic fingerprints for individualised diagnosis, prognosis and treatment of patients takes its place in the centre of translational hepatology. For certain liver diseases personalised therapy approaches are already existent. Examples are the determination of viral genotypes, viral kinetics and genotyping of the IL28B polymorphism to optimise the treatment of chronic hepatitis C. The challenges of the next few years relate to the broadening of the knowledge base, the establishment of reliable and standardised technologies, and the development of intelligent bioinformatics strategies for data analysis and data integration. The following review not only summarises the current state of progress and possibilities of personalised medicine in hepatological diseases, but also explains the technical background of the limitations that currently hinder a consistent clinical implementation.