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In this exclusive interview, Hannes Hagström joins Jörn Schattenberg, Louise Campbell and Roger Green to explore papers emerging from Scandinavia which offer fascinating insights to the field at large.

Hannes opens the conversation with his idea that 2022 was an encouraging year for research, specifically in that the mechanisms of drugs in development “feel more realistic.” When asked what he means by realistic, Hannes explains his interpretation of NAFLD to be a public health problem by which the metabolic system is overloaded with nutrients. He suggests a general pathway would aim to reduce this burden, citing examples like GLP-1s and possibilities surrounding an imminent announcement on resmetirom. From here Hannes describes developing a population-based cohort of liver disease patients using relatively accurate registers in Sweden. He highlights that this system enables studies to navigate issues around selection bias and capture the whole of a population with any diagnosed liver disease dating back to the sixties - roughly 350,000 unique patients in Sweden. The data available in this cohort can be linked back to the general population and used to examine several important research considerations. Long-term outcomes of chronic liver diseases, risk factors for disease progression, impact of dispensed drugs, disease panorama and time trends are among examples.

Segueing to several studies utilizing this cohort, Hannes first introduces a paper which examines cardiovascular disease (CVD) risk and life expectancy in patients with NAFLD compared with the general population. While NAFLD was associated with a higher risk of nonfatal CVD, it notably did not affect post-CVD mortality risk. Another conclusion: patients diagnosed with NAFLD have a lower life expectancy than the general population. Strikingly, this loss in life expectancy was accentuated depending on the age of patient at time of diagnosis. The younger in age one has a diagnosis of NAFLD, the more one can expect to have a drop in life expectancy. Hannes suggests this may summon an urgency in screening younger populations. A caveat of this cohort is noted to be the reality of true incidence rates could be higher than what has been captured in diagnosis in specialty care. At this point, Jörn and Louise ask a series of thought-provoking questions which spur Hannnes to describe additional compelling facets of working with this rich data set. Studies can link research cohorts examining biopsies of patients with NAFLD to these registers, allowing for long-term follow-up. Hannes also mentions collaboration with the Swedish Diabetes Register which captures at least 90% of patients with type 2 diabetes. Such granularity enables investigation into the influence of comorbidities on the risk of liver disease. Roger notes a theme of recent guidelines is to assume that diabetic patients have NAFLD, therefore the recommendation is to immediately search for NASH in the evidence of fibrosis. As these databases are pooled, NAFLD can be examined through a diabetes lens or vice versa. The group goes on to briefly discuss elements of screening, guidelines and the influence of NITs on interpreting prevalence. Hannes bridges this discussion to a just-accepted paper whereby his team looked at developing FIB-4 in a more meaningful way through stratifying subgroups within the overarching risk categories. Simply, the three parameters used are age, presence of diabetes and a gamma-glutamyl transferase test. The latter is noted to be useful in linking cardiac outcomes and an imperfect marker for alcohol use. 

As the session winds down, the panelists explore speculative questions around genetics and the microbiome, and any foresight into how these factors could be filtered through the aforementioned registers and databases. In closing, Hannes provides a gl