Subacute Liver Failure Research Articles

Indications for orthotopic liver transplantation in fulminant liver failure.

The decision to undertake transplantation in a patient with fulminant liver failure requires consideration of many factors so that the physician may arrive at the most appropriate course of action. There are several definitions of fulminant liver failure used in current practice, all excluding patients with chronic liver disease. In the one most recently proposed, the terms hyperacute, acute and subacute liver failure are used to categorize groups of patients with different clinical appearances and progress. Patients in the hyperacute group have a better outcome with medical treatment than others, despite deeper levels of encephalopathy. The decision to proceed to transplantation should be undertaken in patients who fulfil criteria for a poor prognosis with medical management. For two groups, Hôpital Paul Brousse, Paris, and King's College Hospital, London, criteria are based on analysis of large patient numbers, which can be applied at the bedside without recourse to complex analysis. Once a patient has been listed for transplantation, regular systems review must be undertaken because the development of irreversible multiple organ failure may preclude transplantation. Hepatectomy may occasionally have a role in stabilizing a patient awaiting a suitable organ. In less severe cases, auxiliary liver transplantation has been undertaken, and in some patients regeneration of the native liver has occurred, allowing withdrawal of immunosuppressive therapy. The results of orthotopic liver transplantation in fulminant liver failure have steadily improved over recent years, with reported 1-year survival rates of up to 80% in some series, yielding a good prognosis for certain groups of patients who previously had unacceptably high mortality.

Indications for orthotopic liver transplantation in fulminant liver failure

The decision to undertake transplantation in a patient with fulminant liver failure requires consideration of many factors so that the physician may arrive at the most appropriate course of action. There are several definitions of fulminant liver failure used in current practice, all excluding patients with chronic liver disease. In the one most recently proposed, the terms hyperacute, acute and subacute liver failure are used to categorize groups of patients with different clinical appearances and progress. Patients in the hyperacute group have a better outcome with medical treatment than others, despite deeper levels of encephalopathy. The decision to proceed to transplantation should be undertaken in patients who fulfil criteria for a poor prognosis with medical management. For two groups, Hôpital Paul Brousse, Paris, and King's College Hospital, London, criteria are based on analysis of large patient numbers, which can be applied at the bedside without recourse to complex analysis. Once a patient has been listed for transplantation, regular systems review must be undertaken because the development of irreversible multiple organ failure may preclude transplantation. Hepatectomy may occasionally have a role in stabilizing a patient awaiting a suitable organ. In less severe cases, auxiliary liver transplantation has been undertaken, and in some patients regeneration of the native liver has occurred, allowing withdrawal of immunosuppressive therapy. The results of orthotopic liver transplantation in fulminant liver failure have steadily improved over recent years, with reported 1-year survival rates of up to 80% in some series, yielding a good prognosis for certain groups of patients who previously had unacceptably high mortality (Hepatology 1994;20:5S-10S.)

Temporary auxiliary liver transplantation for subacute liver failure in a child

A 4-year-old boy with subacute liver failure due to hepatitis A virus underwent temporary auxiliary liver transplantation. The graft, an adult reduced liver, was implanted othotopically after a left hepatectomy had been carried out on the recipient's liver. Good liver function was immediately restored. The remaining native liver, which was 90% necrotic at the time of transplantation, regained normal histological features within 3 months. The auxiliary graft was then removed and immunosuppressive therapy stopped.

Acute liver failure: redefining the syndromes

Existing definitions of clinical syndromes in acute liver failure do not accurately reflect important differences in clinical features and prognosis. Based on a large series of patients with acute liver failure treated at King's College Hospital, London between 1972 and 1985, we propose a new terminology. Hyperacute liver failure is our suggested term for cases in which encephalopathy occurs within 7 days of the onset of jaundice; this group includes the sizeable cohort likely to survive with medical management despite the high incidence of cerebral oedema. We suggest the term acute liver failure for cases with an interval of between 8 and 28 days from jaundice to encephalopathy; they also have a high incidence of cerebral oedema, but have a much poorer prognosis without liver transplantation. The term subacute liver failure is suggested to describe cases with encephalopathy that occurs within 5 to 12 weeks of the onset of jaundice; these patients are characterised by a low incidence of cerebral oedema, but have a poor prognosis. Adoption of this terminology should help in the management of these patients, in addition to standardising the structure and interpretation of controlled trials of therapies.

Role of hepatitis C virus infection in German patients with fulminant and subacute hepatic failure

To investigate the possible role of hepatitis C virus (HCV) in fulminant and subacute liver failure, we tested serum and liver of 13 patients undergoing orthotopic liver transplantation for the presence of HCV RNA. HCV RNA was detected in specimens from two out of eight patients negative for all viral markers with suspected hepatitis non-A, non-B infection and in one out of four patients with hepatitis B virus infection. Only in this patient replication of HCV could be demonstrated. We conclude, that fulminant and subacute hepatic failure is induced by hepatitis C virus only in few patients with hepatitis non-A, non-B.

Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining.

Little data exist on the proliferative state of liver cells and its relationship with various morphological findings in acute liver failure (ALF) in man. In this study we used the monoclonal antibody NCL-PCNA (clone PC-10) against the proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin sections of 3 normal livers, 14 post-mortem needle-specimens of submassive hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy specimens obtained at transplantation in patients with acute or subacute liver failure of presumed viral aetiology. In normal livers, only occasional sinusoid-lining cells were stained, whereas in SHN following POD or presumed viral hepatitis, hepatocytes of variable morphology showed significant immunoreactivity. Following POD, immunoreactivity was higher in samples taken within 5-6 days than in those obtained at 9-11 days, a pattern reminiscent of the decrease in the rate of regeneration, previously documented after partial hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar 'nodules' in cases with a map-like distribution of collapsed and non-collapsed parenchyma. Ductules demonstrated comparatively less staining, but extensive labelling was exceptionally found in areas of complete hepatocellular dropout. In these areas, small elongated cells with strongly PCNA-positive ovoid nuclei, forming periportal sprouting cords or incorporated into the lining of ductules, were most remarkable in that they closely resembled 'oval cells' described in animal studies.

Does orthotopic liver transplantation heal Wilson's disease? Clinical follow-up of two liver-transplanted patients

Two patients with Wilson's disease (WD) underwent orthotopic liver transplantation, one for subacute liver failure and the other for severe oesophageal haemorrhage. After transplantation both patients fully recovered within five months, and copper metabolism returned to normal. Follow-up examinations were continued for 4 and 6 years. Clinical as well as electrophysiological testing in these two patients yielded better results than in most of 12 WD-patients being conventionally treated for a similar period or even longer.

Flumazenil in the treatment of portal systemic encephalopathy —an overview

Hepatic encephalopathy is a complex neuropsychiatric syndrome associated with acute, subacute and chronic liver failure, involving increased neural inhibition by activation of the GABA/benzodiazepine inhibitory neurotransmitter system. Improvement by GABA and benzodiazepine receptor antagonists as well as by chloride ionophore blockers has been shown in animal experiments. Recent reports indicate that flumazenil may improve hepatic encephalopathy in man. To date 46 episodes of HE in 41 patients have been treated with flumazenil with a short term success rate of 72%. Most of the patients were screened for exogenous benzodiazepines and found negative. These interesting observations should now be investigated in a randomised double-blind controlled study in patients with HE to evaluate the efficiency of this therapy.