Rocahepevirus ratti, like Paslahepevirus balayani, can cause acute hepatitis, chronic hepatitis, and subclinical infection. HEV-C1 infections are self-limiting and less severe than HEV-A infections, characterized by lower mean peak ALT and bilirubin levels in those with intact immunity. In general, the criteria for inclusion in these investigations to identify RHEV infection include clinical and biological manifestations consistent with acute or chronic hepatitis, as well as an ALT level significantly greater than the upper limit of normal. Infections in immunocompromised individuals, on the other hand, are challenging, with 50% of HEV-C1 infections progressing to persistence, according to research by S. Sridhar et al. [18]. This may be due to the fact that immunocompromised people might be more vulnerable to HEV-C1 infections. Not only was the viral pathogenicity examined, but meningoencephalitis was detected as a sequela in an immunocompromised patient after the hepatitis had entirely cured. Therefore, the correlation between RHEV infection and neurological symptoms must be studied. Subclinical HEV-C1 infection, without changes in hepatic function tests or clinical symptoms, is concerning over the safety of blood transfusions because the virus can be transmitted through contaminated blood samples due to the high viral load of HEV-C1 in plasma. RHEV’s viral tropism is oriented towards the liver, with a special affinity for liver cells. Virus replication occurs there, leading to liver damage and the release of liver enzymes into the blood, resulting in acute and chronic hepatitis in humans and animals. Recognizing the pathogenicity is crucial for the development of therapies for the prevention and treatment of hepatitis caused by this virus [18].

Ferrets and rats have been proposed as candidate animal models to study RHEV pathogenesis. Ferrets exhibit three patterns of infection: subclinical infection, acute hepatitis, and persistent infection [56]. Induced infections of RHEV on immunosuppressed rats have shown the effect of high-dose immunosuppression to induce chronic hepatitis and viral load suppression was observed with ribavirin treatment [57].

Molecular biology techniques have facilitated the identification of RHEV RNA in liver, feces, and blood samples obtained from various animal and human species. Such techniques include RT-PCR amplification, Sanger DNA sequencing, and metagenomic tests involving next generation sequencing. The combination of these methods, along with detailed phylogenetic and sequence evaluations, have allowed sequencing of RHEV genomes [4]. The first human RHEV infection was detected in a patient with chronic hepatitis, and this case was validated by RT-PCR and sequencing of plasma, stool, saliva, and liver tissue samples.

The most accurate method for detecting Rocahepevirus ratti infection is the RT-PCR method by which viral genomic RNA can be identified. The sensitivity of the method depends on the design and selection of specific primers. The molecular diagnosis of HEV-A and RHEV may be challenging as several assays have shown low sensitivity for endemic genotypes in Europe and the number of genotypes/subtypes described is increasing, therefore, without an evaluation, their sensitivity in this context is unknown. Primers used to detect human HEV may not be able to recognize the RHEV genome in patient samples, limiting the sensitivity of PCR, and only the use of specific primers for RHEV has allowed its detection in different samples. It is important to note that the genetic diversity of HEV-C1 is still unclear, which could also limit the sensitivity of the techniques [19].

5. Conclusions