Fifty cases of nitrofurantoin-associated hepatic injury and two cases of nifurtoinol (hydroxymethylnitrofurantoin)-associated hepatic injury reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs were analyzed in detail. In 38 cases, a causal relationship was considered likely [i.e., "highly probable" (n = 4), "probable" (n = 23) or "possible" (n = 11)]. In 25 cases, hepatic injury was of the acute type whereas 13 cases presented a chronic type of reaction. Both types were more common in the elderly. Eighty per cent of the acute reactions appeared within the first 6 weeks of treatment and were sometimes accompanied by fever (28%), rash (12%) and eosinophilia (16%). Biochemically, the pattern was mainly hepatocellular (32%), whereas mixed cholestatic-hepatocellular (4%) and cholestatic (4%) patterns were uncommon. Although mild to moderate liver enzyme elevations (60%) were common, these were primarily symptomatic. The reaction was fatal in one "acute" and one "chronic" case. In the chronic cases, nuclear (82%) and smooth muscle (73%) antibodies and LE cells (50%) were frequently present. HLA typing showed no increase of the HLA B8 or HLA DRw3 haplotype. HLA DR2 (56%) and HLA DRw6 (56%) were more frequent than in controls (both 29%), but this was not statistically significant. Histology showed mainly necrosis, varying from spotty to massive, in the acute cases and a pattern consistent with chronic active hepatitis in the chronic cases.(ABSTRACT TRUNCATED AT 250 WORDS)

192 Case reports experienced a histopathologically typical acute rejection episode with marked bile duct injury prior to HCV recurrence, and it is therefore possible that the bile duct injury had, in some way, interfered with the pattern of HCV damage. Third, the use of immunosuppressive agents could have interfered with the immune mediatedor direct cytopathic HCV related injury. This granulomatous bile duct destruction was comparable to the florid duct lesion described as a characteristic feature of PBC and whose presence has recently been used as evidence of PBC recurrence liver grafts6. Because we have shown that such a lesion may also develop as a result of HCV infection in the liver graft of a patient not transplanted for PBC, we believe it should not be considered as the hallmark of PBC. References 1. Lekowitch JH. Sch8 ER, Davis GL et uJ. Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. Gastroenterology 1993: 104: 595-603. 2. Scheuer PJ. Ashrafzadeh P. Serlock S el aJ. The pathology of hepatitis C. Hepatology 1992: 15: 567-571. 3. Bach N. Thung SN. Schaffner F. The histological features ofchronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology 1992: IS: 572-577. 4. Czaja AJ. Carpenter HA. Sensitivity. specificity, and predictability of biopsy interpretations in chronic hepatitis. Gusrroeritmlogy 199 3: 5. Emile JF, Sebagh M. Feray C et al. The presence of epithelioid granulomas in hepatitis C virus-related cirrhosis. Hum. Pathof. 6. Balan V, Batts KP. Poraykho MK et al. Histological evidencc for recurrence of Primary Biliary Cirrhosis after liver transplantation.

The relation between agranular reticulum and glycogen was studied in hepatic cells of female rats. Prolonged fasting of nonadrenalectomized rats did hot result ins complete liver glycogen depletion, whereas in adrenalectomized rats this could be accomplished within a few hours of fasting. In nonadrenalectomized rats a marked development of agranular reticulum associated with glycogen was found, whereas in adrenalectomized rats no such marked development of agranular reticulum was seen during glycogen depletion. Early glycogen restoration in glycogen-depleted liver cells of adrenalectomized rats was brought about 2-4 hr after the injection of 1 dose of cortisone or ½-1 hr after the injection of glucose. Early restoration of glycogen was accompanied and even preceded by a marked development of tubular agranular reticulum. A probable role of this organelle in glycogen synthesis and breakdown is discussed. High resolution autoradiography of tritium-labeled glucose incorporation offered some further illustration on the process of glycogen formation.

No abstract

Eleven cases of hepatic injury attributed to the intake of flucloxacillin were reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs between 1982 and 1992. They concerned four men and seven women, with a mean age of 57 years, treated for 2–28 days with an oral dose varying from 1500–4000 mg per day. Symptoms mostly appeared 10 to 30 days after starting treatment with flucloxacillin. Biochemically, the pattern was compatible with cholestatic hepatitis in seven cases, with a mixed cholestatic‐hepatocellular type of injury in one case, a hepatocellular pattern in two cases, and mild liver enzyme elevations in one patient. Two patients died, one due to fatal bleeding from the liver after biopsy, and the second patient to a combination of hepatic and cardiac failure. The other patients recovered, on average 72 days after peaking of serum aminotransferase values. Histology in seven cases showed cholestatic hepatitis in five, with cholangitis or cholangiolitis in four of these patients. In the other two patients, there was centrilobular cholestasis with extensive bridging fibrosis and portal‐central bridging necrosis, respectively.