**4. Discussion**

Detailed information about natural history of HIV/HCV co-infection is discussed in special review article [27]. Some studies have suggested that human immunodeficiency infection modifies the natural history of hepatitis C virus infection accelerating the progression of fib‐ rosis and the development of cirrhosis [28, 29, 30, 31].

Co-infection HCV/HIV is very often discovered among injecting drug users [32, 33]. Thus, it was shown that about 90% drug users (consumers of heroin) are infected by hepatitis C vi‐ rus [34]. Intravenous heroin abuse induces significant morphological changes in liver tissue (vesicular changes, fatty changes, chronic hepatitis, cirrhosis), and the severity of these changes increases with years of heroin abuse [35]. Authors supposed that worsening of mor‐ phological changes in the liver happens mostly often because of a significantly reduced de‐ toxification functions of the liver.

Espinal, Peréz, Baéz, Hénriguez et al. [36] analyzed the clinical aspects of the co-infection HIV and tuberculosis. Tuberculosis remains an important public health problem in the world that has been exacerbated by HIV epidemic, resulting in increased morbidity and mortality [37, 38]. The pathogenesis and mechanisms of inflammation and accelerated fibro‐ sis in co-infected patients are still poorly understood [28, 39].

At present investigation the peculiarities of patients with heroin abuse and co-infection (TB, HCV and HIV) were analyzed (see Table 1). All the patients were males of the age from 26 to 39 years (mean value was 32.2 years). The heroin abuse was the longest (mean value was 13.6 years). Patients with HCV-infection occupied the second position of disease duration (mean value was 7.1 years), than there were the patients with HIV-infection (mean value was 4.7 years) and finally the patients with TB-infection (mean value was 3.5 years). At last case the tuberculosis was discovered for the first time of 7 patients from 13 patients. It is characteristic that *Mycobacterium tuberculosis* was not discovered in phlegm of any patients under repeated analyses.

We could not detect any interconnections between the quantitative parameters of biopsy specimen getting with the use of computer microscopy and for the duration of above-men‐ tioned observations.

Moreover the tendency to the diseases heaviness increasing is evident. The good example of this tendency is the biopsy specimen № 9: the duration of heroin abuse in this case com‐ posed 15 years, HIV – 13 years, TB – 12 years and HCV – 9 years. In accordance with it the cirrhosis developed in the liver of this patient (see Figure 6) and the segment of non-paren‐ chymal elements reached 27.43%. Among them the specific part of portal zones was preva‐ lent (27.16%).

The other peculiarity was the presence of the same stage of fibrosis (namely fibrosis F2 by METAVIR scoring) and F3 (by Ishak scoring) in liver of the majority of the patients.

At that time the segment of non-parenchyma elements in liver of these patients varied from 2.65% to 11.13%, and the specific part of the portal zones changed from 1.86% to 10.41%. The detailed information about discussion questions and interpretation of liver biopsy assess‐ ment by grading and staging systems was presented in recent works [40, 41].

The typical changes included the destruction of limiting plate, the expansion of portal areas and the development of interface hepatitis, formation of short septa or bridging necroses. The image analysis allows calculating of portal zones areas and intralobular infiltrates in dif‐ ferent fields of biopsy vision. The expansion of portal zones took place especially during the development of interface hepatitis. As a rule, intensive lymphohistiocyte infiltration pre‐ dominates in such a type of portal zones.

The region of intralobular infiltrates strongly varies. Our investigation showed that intralob‐ ular infiltrates developed as a result of lymphocyte-mediated death of hepatocytes (apoptosis).

Earlier we studied the apoptosis in liver biopsy specimens of the patients with HCV with the use of the TUNEL method [42, 43]. TUNEL-marked cells looked as small groups similar to intralobular piecemeal necroses. All morphometric parameters were significantly higher in comparison with monoinfection HCV [8].
