J.C.E. Underwood

Hepatitis C antibody and chronic liver disease in haemophilia.

A radioimmunoassay was used to detect antibodies to hepatitis C virus (anti-HCV) in 154 patients with haemophilia. Prevalence of anti-HCV was associated with exposure to clotting factor concentrates. 76 of 129 (59%) who had received factor VIII or IX had anti-HCV: 42 of 55 (76%) who required over 10,000 units of concentrate annually had anti-HCV, compared with 34 of 74 (46%) who required less, and 0 of 25 patients who had never received concentrates. Anti-HCV were significantly more common in patients seropositive for antibodies against human immunodeficiency virus (anti-HIV) or with markers of previous hepatitis B infection than in those without anti-HIV or hepatitis B markers (88% vs 39% and 75% vs 46%, respectively). 5 of 23 (22%) haemophiliacs treated only with heated concentrates had anti-HCV compared with 71 of 106 (67%) patients who received unmodified products. 35 patients with chronic liver disease underwent liver biopsy: histological examination showed features associated with post-transfusion hepatitis in 24, all of whom were anti-HCV-positive; of the other 11 patients with no histological features of non-A, non-B hepatitis, 5 were anti-HCV-positive. HCV appears to be the major predisposing factor for most non-A, non-B hepatitis and chronic liver disease in haemophilia.

The natural history of chronic hepatitis C in haemophiliacs

Most haemophiliacs treated with non‐virally‐inactivated clotting factor concentrates have been infected with hepatitis C virus (HCV). We have studied the natural history of chronic HCV infection by following all 138 HCV‐positive patients from our centre for periods of up to 28 years. As well as the clinical and biochemical characteristics, we studied 116 liver samples from 63 patients obtained at elective biopsy (n=103) or autopsy (n=13). 36 (26%) of the patients were HIV positive, and three were chronic carriers of hepatitis B. Evidence of previous exposure to hepatitis A and B was found in 37.2% and 48.1% respectively. Raised transaminase levels were found in 82.6% of patients. 11 of 15 patients with normal transaminases tested by PCR for HCV RNA were positive, indicating that most patients, even in this group, have chronic hepatitis C infection. Cirrhosis was diagnosed by liver histology in 19 patients, and nine patients developed liver failure. The incidence of cirrhosis rose rapidly 15 years after HCV infection to 15.6 per 1000 person‐years. Multivariate analysis showed that HIV status, length of time since HCV infection and age at HCV infection were independently associated with both the development of cirrhosis and liver failure. Two patients developed hepatocellular carcinoma; one of these was exposed only to a single batch of FVIII concentrate 11 years earlier. Chronic hepatitis C is increasingly recognized as a major cause for morbidity and mortality in haemophiliacs, especially those who are HIV positive and who were infected at an older age.

Progressive liver disease in haemophilia: an understated problem?

In an 8-year study of 79 unselected patients with haemophilia who had received clotting factor concentrates, there was evidence of chronic progressive liver disease in at least 17 (21%). 8 patients had chronic active hepatitis and 9 had cirrhosis (5 with oesophageal varices). Histological evidence suggested that non-A non-B hepatitis was mainly responsible, although the influence of other viruses could not be excluded. Serial liver biopsies showed progression from chronic persistent hepatitis to chronic active hepatitis and cirrhosis within 6 years, suggesting that chronic persistent hepatitis in haemophiliacs is not as benign as hitherto supposed. Symptoms and abnormal physical signs were uncommon in these patients. There was no relation between degree of abnormality of serum aminotransferase levels and severity of the underlying liver disease. It is anticipated that liver disease in haemophiliacs will become an increasing clinical problem in the future.

KUPFFER-CELL DEPLETION IN CHRONIC LIVER DISEASE: IMPLICATIONS FOR HEPATIC CARCINOGENESIS

It is suggested that the increased incidence of hepatocellular carcinoma complicating cirrhosis may be related to the lobular and nodular depletion of liver macrophages. The occurrence of other hepatic tumours can also be related to the anatomical distribution of these macrophages within the liver. These observations are consistent with the hypothesis that the liver macrophage (Kupffer cell) may play an important role in tumour surveillance.

SYSTEMIC CANDIDIASIS COMPLICATING ACUTE HEPATIC FAILURE IN PATIENTS TREATED WITH CIMETIDINE

Abstract It is suggested that three cases of candida septicaemia complicating acute hepatic failure may have been related to the use of cimetidine in these patients. Suppression of gastric-acid production may permit overgrowth of candida within the gastrointestinal tract, and septicaemia may occur as a consequence of the impaired cellular immunity shown by patients with liver failure.

Phagocytic function in the isolated perfused rat liver: An experimental model

An experimental model for measuring the phagocytic function of the isolated perfused rat liver is described. A progressive rise in phagocytosis was observed with increasing liver blood flow. This is due to an increase in total particle uptake by the liver with no alteration in the rate constant for phagocytosis except at the highest flow rate. Phagocytosis is substantially greater in the livers of 100-day-old rats than in 21-day-old rats, but the number of particles ingested per unit weight by the older rats is significantly less. Liver phagocytosis is shown to be both temperature- and oxygen-dependent, but independent of nutritional status and animal gender. This model may be useful for assessing the effects of drugs and toxins on hepatic phagocytosis.