Brendan M. McGuire

Background & Aims: The long‐term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. The aim of this study was to provide an overview of the 2‐year clinical outcomes among initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrolment in the Acute Liver Failure Study Group (ALFSG).Methods: Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed.Results: Two‐year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous survivors (SS) (89.5%) and 200 non‐APAP SS (75.5%) (P < 0.0001). The causes of death were similar in the three groups but the time to death was significantly longer in the LT recipients (P < 0.0001). Independent predictors of 2‐year mortality in the APAP group were a high serum phosphate level and patient age (c‐statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non‐APAP group (c‐statistic = 0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c‐statistic = 0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level (P < 0.05).Conclusions: Two‐year outcomes in initial survivors of ALF are generally good but non‐APAP patients have a significantly lower survival which may relate to pre‐existing medical comorbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow‐up from ongoing psychiatric and substance abuse issues.

Current trends in the treatment of hepatic encephalopathy Mohamad Rasm Al Sibae, Brendan M McGuireDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA Hepatic encephalopathy (HE) is a common reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction and significant morbidity and mortality. Although a clear pathogenesis is yet to be determined, elevated ammonia in the serum and central nervous system are the mainstay for pathogenesis and treatment. Management includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and use of benzodiazepines, psychoactive drugs, and/or alcohol). Clinical trials have established the efficacy of lactulose and lactitol enemas in the treatment of acute hepatic encephalopathy. Extensive clinical experience has demonstrated the efficacy of oral lactulose and lactitol with the goal of two to three soft bowel movements a day for the treatment of chronic HE. However, lactulose and lactitol have significant gastrointestinal side effects. For patients unable to tolerate lactulose or lactitol or who still have persistent chronic HE with lactulose or lactitol, neomycin, metronidazole and rifaximin are second-line agents. More recent data supports the benefits of rifaximin used solely and as an additional agent with fewer side effects than neomycin or metronidazole. Newer therapies being investigated in humans with clinical promise include nitazoxanide, the molecular adsorbent recirculating system (MARS), L-ornithine phenylacetate, sodium benzoate, and/or sodium phenylacetate and Kremezin® (AST-120).Keywords: hepatic encephalopathy, liver dysfunction, lactulose, lactitol

Hepatic encephalopathy (HE) is a broad spectrum of neuropsychiatric manifestations usually affecting individuals with end-stage liver disease. The presence of HE is a poor prognostic sign, with 1-year mortality rates of almost 60%. There is much debate about the underlying mechanisms that result in this syndrome; however, elevated plasma and central nervous system ammonia levels are considered key factors in its pathogenesis. Initial evaluation of the patient presenting with overt HE should include a careful search for predisposing factors, including underlying infection, gastrointestinal (GI) bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and excessive use of benzodiazepines, psychoactive drugs, or alcohol. The mainstay of treatment for many years has been nonabsorbable disaccharides, particularly lactulose. Alternative treatments, which usually are second line in patients who do not respond to lactulose, include zinc, antibiotics (neomycin, metronidazole, and rifaximin), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention. Accepted treatments for HE are associated with significant unpleasant side effects, including diarrhea, renal failure, neuropathy, and other GI disturbance. Newer therapies are still in development, and most are awaiting human trials in order to confirm their benefit. These include manganese chelators, L-carnitine, N-methyl-D-aspartate receptor antagonists, blood purification dialysis system, and an intravenous combination of sodium benzoate and phenylacetate.

Patients infected with hepatitis C virus (HCV) frequently develop renal failure after liver transplantation. To describe renal histologic characteristics and concomitant clinical features in HCV-infected patients with end-stage cirrhosis. Case series. Single-center liver transplant program in the United States. 30 patients who received liver transplants for HCV-induced cirrhosis. Kidney biopsy during liver engraftment. Clinical data and laboratory tests of renal function within 6 months before liver transplantation. Twenty-five patients had immune-complex glomerulonephritis: membranoproliferative glomerulonephritis type 1 (n = 12), IgA nephropathy (n = 7), and mesangial glomerulonephritis (n = 6). Of these patients, 10 had normal serum creatinine levels, normal urinalysis results, and normal quantitative proteinuria. For 5 others, the only renal abnormality was an increased serum creatinine level. No patient had cryoglobulins in the blood or kidney. This small observational study did not include patients with nonviral cirrhosis and did not document post-transplantation outcomes. Immune-complex glomerulonephritis was common in patients with end-stage HCV-induced cirrhosis and was often clinically silent. Its potential to cause renal failure after liver transplantation may be underappreciated.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13–56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15–29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival. (Liver Transpl 2005;11:1590–1596.)

Fulminant hepatic failure is a challenging medical condition that requires intensive care management to prevent-major complications (cerebral edema, infections, and multi-system organ failure) and assistance from a liver transplant team when it is believed that liver regeneration is unlikely. Unfortunately, there are no specific medical therapies or devices to correct all of the functions of a liver. N-acetylcysteine is used for the treatment of acetaminophen overdose, but for most other causes of fulminant hepatic failure therapy is supportive care. This case illustrates many of the problems that are encountered during medical management of fulminant hepatic failure.