Recent breakthroughs in hepatic disease treatment
Key Takeaways
Gastroenterologists, take note—exciting new breakthroughs in hepatology have significant implications for patient care.
New treatments and insights are related to hepatitis B and C, colorectal cancer, liver disease, and Crigler-Najjar syndrome.
The MELD score assessment has been updated to provide a more accurate calculation while prioritizing liver transplant candidates aged 12 and over.
The field of hepatology is in rapid transition. Breakthroughs once considered remote are changing the way we think about and treat hepatic disease.
Notable achievements include the successful eradication of hepatitis C infection through direct-acting antivirals; sustained viral suppression in patients with hepatitis B who are treated with entecavir or tenofovir; and the evolution of liver transplantation from a high-risk procedure to a standard of care for patients with end-stage liver disease.[]
This era of innovation continues to yield unprecedented advancements in the field, propelling hepatology into a realm of continual progress.
PLA predictions
Colorectal cancer damages the mucosal barrier and permits bacteria to invade the bloodstream and portal system. Pyogenic liver abscess (PLA) and other infections are linked to colorectal cancer.
Results of a recent meta-analysis has demonstrated that the incidence of colorectal cancer in patients with PLA is 7-fold higher compared with patients without PLA. These statistics, however, are predominantly based on Southeast Asian populations.[]
Among a population of US veterans, investigators found that there was a higher incidence of colorectal cancer within 3 years of PLA diagnosis during a period of 18 years (n=8826 patients at 127 Veterans Affairs hospitals).[]
This association was not significant, however, after 3 years. The association was observed in Black patients, White patients, and patients with cryptogenic PLA, but not in patients with PLA likely secondary to biliary infection. The mortality hazard was higher in patients with colorectal cancer diagnosed within 6 months of a PLA diagnosis than in patients with colorectal cancer who did not have PLA.
Putting their study in perspective, the authors wrote, “Despite preliminary data suggesting that patients who experienced PLA have a higher CRC [colorectal cancer] incidence, there are no professional guidelines to recommend CRC screening for patients who are diagnosed with PLA. In addition, epidemiologic studies about this association are mainly from Southeast Asia, with a few studies available from the US, where population risk factors for CRC and availability of CRC screening are greatly different from those in Southeast Asian countries.”
MELD 3.0 update
The Model for End-stage Liver Disease (MELD) guides liver transplantation. The Organ Procurement and Transplantation Network implemented an updated score called MELD 3.0, for prioritizing liver transplantation candidates aged 12 years or older.[]
MELD 3.0 enhances the accuracy of the MELD calculation in the following ways:[]
• By incorporating additional variables, including albumin and sex;
• By updating coefficients for existing variables;
• By adding interaction terms;
• And by decreasing the maximum creatinine value from 4.0 to 3.0 mg/dL.
Gene therapy for Crigler-Najjar
In a recent phase 1/2 study, published in the NEJM, researchers assessed the efficacy of a single intravenous infusion of adeno-associated virus serotype 8 vector encoding UGT1A1 in patients with Crigler–Najjar syndrome. All of the patients were being treated with phototherapy.[]
No serious adverse effects were observed. The most common adverse events were headache and increases in liver enzymes.
Patients who received the higher dose experienced restored UGT1A1 activity to levels that allowed the suspension of phototherapy. Efficacy continued at 18 months post-treatment.
The study authors explained, “In gene transfer with the use of AAV vectors, a series of events needs to occur in order to achieve long-term expression of the transgene in the target cells. After the vector genome is stabilized in its episomal form, expression is expected to be durable."
"In some studies, a peak in expression has been observed shortly after vector administration, reaching a lower plateau thereafter."
— Authors, NEJM
"It is hypothesized that this phenomenon is the result of the expression of transient forms of the AAV vector genome. Alternatively, epigenetic silencing may occur, or overexpression of the transgene may trigger endoplasmic reticulum stress and transduced cell death,” the authors concluded.
What this means for you
Hepatology continues to be a field in rapid flux. Recent advancements include the eradication of hepatitis C infection and sustained viral suppression in hepatitis B patients, as well as transformative changes in liver transplantation. At the same time, new studies suggest a potential association between pyogenic liver abscess and colorectal cancer, and promising results were observed in a gene therapy study for Crigler-Najjar syndrome. All of these innovations indicate progress in the field, with significant implications for patient care.