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Introduction: Treatment is generally not available for drug-induced liver injury (DILI) patients except in some specific circumstances. The management of DILI is based on the withdrawal of the responsible drug and monitoring the patients and only a few patients need to be referred to a transplant center. Some studies on the role of ursodeoxycholic acid (UDCA) in DILI have been published. The aim of this study was to perform a systematic review of the role of UDCA in the treatment and prevention of DILI.Methods: A search was undertaken in PubMed, with the key words ursodeoxycholic acid, drug-induced liver injury and hepatotoxicity following the PRISMA guidelines.Results: A total of 33 publications were identified: 25 case reports and 8 case series. In 18 of the 25 cases reports (22 patients), authors reported improvement of liver injury associated with UDCA therapy whereas 7 case reports did not show clinical or biochemical improvement after UDCA treatment. There were 4 studies evaluating the role of UDCA in the treatment of DILI, three prospective (one being a clinical trial) and one retrospective studies. Three studies observed liver profile improvements associated with UDCA. In addition, four studies evaluated UDCA in the prevention of DILI: one pilot study, two randomized clinical trials (RCT) and one retrospective study. Three of these studies observed a lower percentage of patients with an increase in transaminases in the groups that used UDCA for DILI prevention.Conclusion: According to available data UDCA seems to have some benefits in the treatment and prevention of DILI. However, the design of the published studies does not allow a firm conclusion to be drawn on the efficacy of UDCA in DILI. A well designed RCT to evaluate the role of UDCA in DILI is needed.

Objective The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. Background Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. Methods Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. Results Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. Conclusions Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis.

Sir,Chronic cholestatic liver diseases typically comprise primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), previously called primary biliary cirrhosis. Both diseases are ...

Colonic motor function is modulated by extended and local neural reflexes involving unknown mediators. To test the role of serotonin (5-HT3) pathways, increases in colonic tone during antral distension and duodenal lipid perfusion (gastrocolonic responses) and changes in orad and caudad colonic tone in response to local colonic distension (peristaltic reflex) were measured after double-blind granisetron (10 μg/kg) or placebo infusion in healthy human volunteers. Antral distension evoked increases in colonic tone, which were blunted by granisetron ( P < 0.05) without effects on antral compliance. Intraduodenal lipid perfusion also evoked increased colonic tone, which was reduced by granisetron ( P < 0.05). In contrast, orad colonic contractions and caudad relaxations and contractions during colonic distension were unaffected by granisetron. In conclusion, 5-HT3 receptor antagonism blunts both the mechano- and chemoreceptor components of the human gastrocolonic response without altering antral compliance. In contrast, 5-HT3 pathways play no role in the ascending or descending components of the colonic peristaltic reflex. These findings demonstrate different roles for 5-HT3 receptors in the control of colonic motor function by the proximal gastrointestinal tract and by local neural reflexes.

In general, if a patient survives idiosyncratic DILI, then no long-term consequences on liver function are to be expected. However, severe DILI associated with jaundice may induce progressive liver disease in a small proportion of individuals despite drug withdrawal. A number of drugs have been shown to induce autoimmune hepatitis. In addition, the development of liver cirrhosis has been reported for several different drugs. Some drugs with a cholestatic type of injury have been associated with the development of vanishing bile duct syndrome, with long-term persistent liver injury. Although it seems well documented that chronic liver injury can occur after DILI and discontinuation of drug therapy, the long-term consequences in terms of liver-related morbidity and mortality are unclear. It has been shown that chronic liver disease including cirrhosis is very rare but chronic liver disease due to drugs can occur and may contribute to cases of cryptogenic cirrhosis.