NASH: A Case for Personalized Treatment
NASH: A Case for Personalized Treatment
There are four important considerations prior to treating patients with NASH. First, general lifestyle modifications through dietary changes and increased activity may help primarily cardiovascular risk factors that are commonly seen in patients with NASH. Nevertheless, some benefit from the liver standpoint may also be accomplished with adequate weight loss. Second, treatment regimens for liver disease should be focused on those NAFLD patients with histologically proven NASH due to the potentially progressive course of this type of chronic liver disease. Third, treatment regimens must target the pathogenic pathway that is prominent in the specific patient with NASH. Fourth, prior to carrying out a clinical trial for treatment of NASH, it must be clearly stated what the outcomes will be and the importance of each outcome both from efficacy and safety standpoints.
Obviously, the most important clinical outcome for patients with NASH is improving their survival. Given the very slow progressive nature of NASH, only surrogate markers of this important clinical outcome can be used. There has been a great deal of debate and confusion about the validity and appropriateness of different surrogate markers in predicting the long-term survival of patients with NASH. In fact, clinical data and laboratory tests (such as aminotransferases) may have very limited utility in predicting liver-related mortality. These clinical and laboratory tests may have better utility for predicting advanced hepatic fibrosis, but not mortality. Histological stage of hepatic fibrosis may be a better predictor of mortality. In a recent study, after considering clinical and pathological parameters, only histological fibrosis was the best predictor of liver-related mortality. Studies have also shown that liver enzymes, presence of insulin resistance (IR) as well as histological ballooning of hepatocytes are associated with NASH-related fibrosis. Grade of hepatic steatosis by radiological modalities or pathology has not been, predictive of this important clinical outcome.
Over the past two decades, a large number of clinical trials have been carried out to treat NASH. Except for a few recent studies, most did not follow these basic design requirements for clinical trials of NASH. The results of these studies have been quite disappointing and have not led to a clear recommendation of a single strategy to treat patients with NASH. In the following paragraphs, we will summarise the results of some of these different modalities used for treatment of patients with NASH and NAFLD.
General Issues Related to Treatment of NASH
There are four important considerations prior to treating patients with NASH. First, general lifestyle modifications through dietary changes and increased activity may help primarily cardiovascular risk factors that are commonly seen in patients with NASH. Nevertheless, some benefit from the liver standpoint may also be accomplished with adequate weight loss. Second, treatment regimens for liver disease should be focused on those NAFLD patients with histologically proven NASH due to the potentially progressive course of this type of chronic liver disease. Third, treatment regimens must target the pathogenic pathway that is prominent in the specific patient with NASH. Fourth, prior to carrying out a clinical trial for treatment of NASH, it must be clearly stated what the outcomes will be and the importance of each outcome both from efficacy and safety standpoints.
Obviously, the most important clinical outcome for patients with NASH is improving their survival. Given the very slow progressive nature of NASH, only surrogate markers of this important clinical outcome can be used. There has been a great deal of debate and confusion about the validity and appropriateness of different surrogate markers in predicting the long-term survival of patients with NASH. In fact, clinical data and laboratory tests (such as aminotransferases) may have very limited utility in predicting liver-related mortality. These clinical and laboratory tests may have better utility for predicting advanced hepatic fibrosis, but not mortality. Histological stage of hepatic fibrosis may be a better predictor of mortality. In a recent study, after considering clinical and pathological parameters, only histological fibrosis was the best predictor of liver-related mortality. Studies have also shown that liver enzymes, presence of insulin resistance (IR) as well as histological ballooning of hepatocytes are associated with NASH-related fibrosis. Grade of hepatic steatosis by radiological modalities or pathology has not been, predictive of this important clinical outcome.
Over the past two decades, a large number of clinical trials have been carried out to treat NASH. Except for a few recent studies, most did not follow these basic design requirements for clinical trials of NASH. The results of these studies have been quite disappointing and have not led to a clear recommendation of a single strategy to treat patients with NASH. In the following paragraphs, we will summarise the results of some of these different modalities used for treatment of patients with NASH and NAFLD.
